Ignite Creation Date:
2025-12-24 @ 12:39 PM
Ignite Modification Date:
2026-03-01 @ 6:02 AM
Study NCT ID:
NCT03621761
Status:
COMPLETED
Last Update Posted:
2022-12-27
First Post:
2018-08-03
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Cognitive Behavioral Therapy, Modafinil, or Both for Multiple Sclerosis Fatigue
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2022-10-27', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}, {'id': 'D005221', 'term': 'Fatigue'}], 'ancestors': [{'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077408', 'term': 'Modafinil'}], 'ancestors': [{'id': 'D001559', 'term': 'Benzhydryl Compounds'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'tbraley@med.umich.edu', 'phone': '734-232-1147', 'title': 'Tiffany Braley', 'organization': 'University of Michigan'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '25 weeks, AE data was collected for 25 weeks from consent, in line with 24 week exploratory outcome measures.', 'eventGroups': [{'id': 'EG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.', 'otherNumAtRisk': 114, 'deathsNumAtRisk': 114, 'otherNumAffected': 1, 'seriousNumAtRisk': 114, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).', 'otherNumAtRisk': 114, 'deathsNumAtRisk': 114, 'otherNumAffected': 12, 'seriousNumAtRisk': 114, 'deathsNumAffected': 1, 'seriousNumAffected': 4}, {'id': 'EG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).', 'otherNumAtRisk': 108, 'deathsNumAtRisk': 108, 'otherNumAffected': 19, 'seriousNumAtRisk': 108, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 8}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 8}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 9}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 6}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'MS relapse/exacerbation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Benign paroxysmal vertigo', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Cerebrospinal fluid leakage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Localized edema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Trigeminal neuralgia pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Surgical/Medical procedure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 114, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 114, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 108, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in the Modified Fatigue Impact Scale (MFIS) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'OG000'}, {'value': '114', 'groupId': 'OG001'}, {'value': '108', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.'}, {'id': 'OG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'OG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}], 'classes': [{'categories': [{'measurements': [{'value': '-15.2', 'spread': '11.9', 'groupId': 'OG000'}, {'value': '-16.0', 'spread': '15.9', 'groupId': 'OG001'}, {'value': '-17.3', 'spread': '16.2', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.3451', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '1.7740', 'groupDescription': 'Comparison of treatment effect of CBT monotherapy vs. combination therapy (reference) on total MFIS score, in linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline MFIS score. Output reflects models that were imputed for missing data.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.4834', 'groupIds': ['OG001', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '1.3094', 'groupDescription': 'Comparison of treatment effect of modafinil monotherapy vs. combination therapy (reference) on total MFIS score, in linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline MFIS score. Output reflects models that were imputed for missing data.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline-12 weeks', 'description': "The Modified Fatigue Impact Scale is a 21-item self-report survey. Each item is rated 0-4, Total scores range from 0-84. . Higher scores indicate a greater impact of fatigue on a person's activities. The primary outcome measure will be the mean within-subject difference between baseline and 12-week Modified Fatigue Impact Scale values (delta-MFIS), compared between the 3 treatment groups.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Fatigue Intensity as Assessed by Self-reported Numerical Rating Scale (NRS) Score.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '88', 'groupId': 'OG000'}, {'value': '91', 'groupId': 'OG001'}, {'value': '93', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.'}, {'id': 'OG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'OG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.41', 'spread': '2.43', 'groupId': 'OG000'}, {'value': '-1.69', 'spread': '2.33', 'groupId': 'OG001'}, {'value': '-2.03', 'spread': '2.82', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.2570', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.4077', 'groupDescription': 'Comparison of treatment effect of CBT monotherapy vs. combination therapy (reference) on change in EMA fatigue intensity NRS score, in complete case linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline EMA fatigue intensity score.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.5017', 'groupIds': ['OG001', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '-0.2452', 'groupDescription': 'Comparison of treatment effect of modafinil monotherapy vs. combination therapy (reference) on change in EMA fatigue intensity NRS score, in complete case linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline EMA fatigue intensity score.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline-12 weeks', 'description': 'Fatigue intensity was assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. Using a 0-10 numerical rating scale, participants entered fatigue intensity ratings into the user-interface on the PRO-Diary 4 times each day, for 7 days, at baseline (pre-intervention) and at 12 weeks post-intervention. All scores over the 7 days were averaged to produce an aggregate fatigue intensity score. Higher scores indicate greater fatigue intensity. Change in fatigue intensity between baseline and 12 weeks was compared between the 3 treatment groups.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Some participants who completed the study did not complete their 12-week Pro-Diary entries.'}, {'type': 'SECONDARY', 'title': 'Change in Fatigue Interference as Assessed by Self-reported Numerical Rating Scale (NRS) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '88', 'groupId': 'OG000'}, {'value': '91', 'groupId': 'OG001'}, {'value': '93', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.'}, {'id': 'OG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'OG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.41', 'spread': '2.60', 'groupId': 'OG000'}, {'value': '-1.73', 'spread': '2.52', 'groupId': 'OG001'}, {'value': '-1.78', 'spread': '2.98', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.154', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.095', 'groupDescription': 'Comparison of treatment effect of CBT monotherapy vs. combination therapy (reference) on change in EMA fatigue interference NRS score, in complete case linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline EMA fatigue interference score.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.610', 'groupIds': ['OG001', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.034', 'groupDescription': 'Comparison of treatment effect of modafinil monotherapy vs. combination therapy (reference) on change in EMA fatigue interference NRS score, in complete case linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline EMA fatigue interference score.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline-12 weeks', 'description': 'Fatigue interference will be assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. Using a 0-10 numerical rating scale, participants entered fatigue interference ratings into the user-interface on the PRO-Diary 4 times each day, for 7 days, at baseline (pre-intervention) and at 12 weeks post-intervention. All scores over the 7 days were averaged to produce an aggregate fatigue impact score. Higher scores indicate greater fatigue impact. Change in fatigue interference between baseline and 12 weeks will be compared between the 3 treatment groups.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'A few participants in each arm who stayed in the study, did not complete the NRS Survey at 12 weeks.'}, {'type': 'SECONDARY', 'title': 'Change in Fatigability as Assessed by the Self-reported Fatigue Intensity Numerical Rating Scale (NRS) Score and Physical Activity Level', 'denoms': [{'units': 'Participants', 'counts': [{'value': '83', 'groupId': 'OG000'}, {'value': '83', 'groupId': 'OG001'}, {'value': '86', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.'}, {'id': 'OG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'OG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.0041', 'spread': '0.0476', 'groupId': 'OG000'}, {'value': '-0.0175', 'spread': '0.0320', 'groupId': 'OG001'}, {'value': '-0.0075', 'spread': '0.0404', 'groupId': 'OG002'}]}]}], 'analyses': [{'pValue': '0.4955', 'groupIds': ['OG000', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '0.00427', 'groupDescription': 'Comparison of treatment effect of CBT monotherapy vs. combination therapy (reference) on change in fatigability score, in complete case linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline fatigability score.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.1333', 'groupIds': ['OG001', 'OG002'], 'paramType': 'Slope', 'ciNumSides': 'TWO_SIDED', 'paramValue': '-0.00948', 'groupDescription': 'Comparison of treatment effect of modafinil monotherapy vs. combination therapy (reference) on change in fatigability score, in complete case linear regression models adjusted for age, sex, anxiety, pain, activity level, study site, and baseline fatigability score.', 'statisticalMethod': 'Regression, Linear', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline-12 weeks', 'description': "Fatigability will be assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. The fatigability score will be calculated as the ratio of the self-reported fatigue intensity rating (using a 0-10 numerical rating score) divided by the participant's concurrent physical activity level (measured as the average number of activity counts per minute via actigraphy). All fatigability scores will be averaged over the 7 days to create an aggregate fatigability score. Higher scores indicate greater fatigability. Change in fatigability between baseline and 12 weeks will be compared between the 3 treatment groups.", 'unitOfMeasure': 'score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Some participants in the study did not complete their 12-week Pro-Diary entries.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.'}, {'id': 'FG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'FG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '114'}, {'groupId': 'FG001', 'numSubjects': '114'}, {'groupId': 'FG002', 'numSubjects': '108'}]}, {'type': 'Week 8 Follow-up Timepoint', 'achievements': [{'groupId': 'FG000', 'numSubjects': '111'}, {'groupId': 'FG001', 'numSubjects': '111'}, {'groupId': 'FG002', 'numSubjects': '105'}]}, {'type': 'Week 12 Follow-up Timepoint', 'achievements': [{'groupId': 'FG000', 'numSubjects': '111'}, {'groupId': 'FG001', 'numSubjects': '110'}, {'groupId': 'FG002', 'numSubjects': '105'}]}, {'type': 'Week 24 Survey Timepoint', 'achievements': [{'groupId': 'FG000', 'numSubjects': '111'}, {'groupId': 'FG001', 'numSubjects': '110'}, {'groupId': 'FG002', 'numSubjects': '105'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '111'}, {'groupId': 'FG001', 'numSubjects': '110'}, {'groupId': 'FG002', 'numSubjects': '105'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '4'}, {'groupId': 'FG002', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '2'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '1'}, {'groupId': 'FG002', 'numSubjects': '1'}]}, {'type': 'Became Ineligible', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Participants were recruited based on physician or clinic referral at two university medical centers, social media advertising, web site postings, email, letter, and phone calls to participants on our health registries. The first participant was enrolled on November 15, 2018 and the last participant was enrolled on June 2, 2021.', 'preAssignmentDetails': 'Of 343 enrolled participants, 336 met inclusion criteria and were randomized to treatment.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.'}, {'id': 'BG001', 'title': 'Modafinil', 'description': '50-400 mg per day (oral)\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'BG002', 'title': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)\n\nTelephone-based Cognitive Behavioral Therapy: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.\n\nModafinil: Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '48.8', 'spread': '11.6', 'groupId': 'BG000'}, {'value': '47.4', 'spread': '11.7', 'groupId': 'BG001'}, {'value': '49.1', 'spread': '11.3', 'groupId': 'BG002'}, {'value': '48.8', 'spread': '11.6', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '85', 'groupId': 'BG000'}, {'value': '93', 'groupId': 'BG001'}, {'value': '78', 'groupId': 'BG002'}, {'value': '256', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '29', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '30', 'groupId': 'BG002'}, {'value': '80', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'title': 'Ethnicity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}, {'value': '18', 'groupId': 'BG003'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '102', 'groupId': 'BG000'}, {'value': '106', 'groupId': 'BG001'}, {'value': '97', 'groupId': 'BG002'}, {'value': '305', 'groupId': 'BG003'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}, {'value': '13', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'American Indian or Alaska Native', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}, {'title': 'Asian', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}, {'value': '4', 'groupId': 'BG003'}]}]}, {'title': 'Black or African American', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}, {'value': '21', 'groupId': 'BG003'}]}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}, {'title': 'White', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '96', 'groupId': 'BG000'}, {'value': '98', 'groupId': 'BG001'}, {'value': '92', 'groupId': 'BG002'}, {'value': '286', 'groupId': 'BG003'}]}]}, {'title': 'Other', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}, {'value': '5', 'groupId': 'BG003'}]}]}, {'title': 'Missing', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}, {'value': '1', 'groupId': 'BG003'}]}]}, {'title': 'Bi/Multi-Racial', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}, {'value': '19', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'denoms': [{'units': 'Participants', 'counts': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '114', 'groupId': 'BG000'}, {'value': '114', 'groupId': 'BG001'}, {'value': '108', 'groupId': 'BG002'}, {'value': '336', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Modified Fatigue Impact Scale (MFIS) Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '104', 'groupId': 'BG000'}, {'value': '106', 'groupId': 'BG001'}, {'value': '101', 'groupId': 'BG002'}, {'value': '311', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '52.6', 'spread': '13.7', 'groupId': 'BG000'}, {'value': '53.2', 'spread': '14.4', 'groupId': 'BG001'}, {'value': '52.3', 'spread': '14.1', 'groupId': 'BG002'}, {'value': '52.7', 'spread': '14.1', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': "The Modified Fatigue Impact Scale is a self-report survey that contains 21 items. Each item is rated 0-4. Higher scores indicate a greater impact of fatigue on a person's daily life. Total scores range from 0 - 84.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Baseline MFIS results (means/SD) are based on the number of participants who completed the entire survey at baseline. 10 participants in the CBT group, 8 participants in the combination group, and 7 in the modafinil group had incomplete survey results.'}, {'title': 'Fatigue Intensity as Assessed by Self-reported Numerical Rating Scale (NRS) Score.', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '107', 'groupId': 'BG000'}, {'value': '111', 'groupId': 'BG001'}, {'value': '105', 'groupId': 'BG002'}, {'value': '323', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '9.2', 'spread': '2.9', 'groupId': 'BG000'}, {'value': '9.0', 'spread': '3.2', 'groupId': 'BG001'}, {'value': '8.8', 'spread': '3.0', 'groupId': 'BG002'}, {'value': '9.0', 'spread': '3.0', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': 'Fatigue intensity was assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface.\n\nUsing a 0-10 numerical rating scale, participants rated their fatigue intensity on the user-interface of the PRO-Diary four times each day, for 7 days, at baseline (pre-intervention). All scores over the 7 days are averaged to produce an aggregate fatigue intensity score. Higher scores indicate greater fatigue intensity.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': '7 participants in the CBT group, 3 participants in the combination therapy group, and 3 participants in the modafinil group were missing baseline EMA fatigue intensity data.'}, {'title': 'Fatigue Interference as Assessed by Self-reported Numerical Rating Scale (NRS) Score', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '107', 'groupId': 'BG000'}, {'value': '111', 'groupId': 'BG001'}, {'value': '105', 'groupId': 'BG002'}, {'value': '323', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '7.75', 'spread': '3.15', 'groupId': 'BG000'}, {'value': '7.33', 'spread': '3.52', 'groupId': 'BG001'}, {'value': '7.30', 'spread': '3.32', 'groupId': 'BG002'}, {'value': '7.5', 'spread': '3.3', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': 'Fatigue intereference was assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface.\n\nUsing a 0-10 numerical rating scale, participants rated their fatigue impact, and entered the score into the user-interface on the PRO-Diary four times each day, for 7 days, at baseline (pre-intervention). All scores over the 7 days are averaged to produce an aggregate fatigue interference score. Higher scores indicate greater fatigue interference.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': '7 participants in the CBT group, 3 participants in the combination therapy group, and 3 participants in the modafinil group were missing baseline EMA fatigue interference data.'}, {'title': 'Fatigability as Assessed by the Self-reported Fatigue Intensity Numerical Rating', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '107', 'groupId': 'BG000'}, {'value': '108', 'groupId': 'BG001'}, {'value': '100', 'groupId': 'BG002'}, {'value': '315', 'groupId': 'BG003'}]}], 'categories': [{'measurements': [{'value': '0.07', 'spread': '0.04', 'groupId': 'BG000'}, {'value': '0.07', 'spread': '0.04', 'groupId': 'BG001'}, {'value': '0.07', 'spread': '0.07', 'groupId': 'BG002'}, {'value': '0.07', 'spread': '0.05', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'description': "Fatigability was assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. The fatigability score is calculated as the ratio of the self-reported fatigue intensity rating (using a 0-10 numerical rating score) divided by the participant's concurrent physical activity level (measured as the average number of activity counts per minute). All fatigability scores are averaged over the 7 days to create an aggregate fatigability score. Higher scores indicate greater fatigability.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': '7 participants in the CBT group, 3 participants in the combination therapy group, and 3 participants in the modafinil group were missing baseline EMA fatigability data.'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-05-07', 'size': 679839, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_001.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2022-11-01T12:41', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR'], 'maskingDescription': 'Rater blinded'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 343}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-11-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-12', 'completionDateStruct': {'date': '2021-11-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-12-05', 'studyFirstSubmitDate': '2018-08-03', 'resultsFirstSubmitDate': '2022-10-03', 'studyFirstSubmitQcDate': '2018-08-03', 'lastUpdatePostDateStruct': {'date': '2022-12-27', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2022-12-05', 'studyFirstPostDateStruct': {'date': '2018-08-08', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2022-12-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-08-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in the Modified Fatigue Impact Scale (MFIS) Score', 'timeFrame': 'Baseline-12 weeks', 'description': "The Modified Fatigue Impact Scale is a 21-item self-report survey. Each item is rated 0-4, Total scores range from 0-84. . Higher scores indicate a greater impact of fatigue on a person's activities. The primary outcome measure will be the mean within-subject difference between baseline and 12-week Modified Fatigue Impact Scale values (delta-MFIS), compared between the 3 treatment groups."}], 'secondaryOutcomes': [{'measure': 'Change in Fatigue Intensity as Assessed by Self-reported Numerical Rating Scale (NRS) Score.', 'timeFrame': 'Baseline-12 weeks', 'description': 'Fatigue intensity was assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. Using a 0-10 numerical rating scale, participants entered fatigue intensity ratings into the user-interface on the PRO-Diary 4 times each day, for 7 days, at baseline (pre-intervention) and at 12 weeks post-intervention. All scores over the 7 days were averaged to produce an aggregate fatigue intensity score. Higher scores indicate greater fatigue intensity. Change in fatigue intensity between baseline and 12 weeks was compared between the 3 treatment groups.'}, {'measure': 'Change in Fatigue Interference as Assessed by Self-reported Numerical Rating Scale (NRS) Score', 'timeFrame': 'Baseline-12 weeks', 'description': 'Fatigue interference will be assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. Using a 0-10 numerical rating scale, participants entered fatigue interference ratings into the user-interface on the PRO-Diary 4 times each day, for 7 days, at baseline (pre-intervention) and at 12 weeks post-intervention. All scores over the 7 days were averaged to produce an aggregate fatigue impact score. Higher scores indicate greater fatigue impact. Change in fatigue interference between baseline and 12 weeks will be compared between the 3 treatment groups.'}, {'measure': 'Change in Fatigability as Assessed by the Self-reported Fatigue Intensity Numerical Rating Scale (NRS) Score and Physical Activity Level', 'timeFrame': 'Baseline-12 weeks', 'description': "Fatigability will be assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. The fatigability score will be calculated as the ratio of the self-reported fatigue intensity rating (using a 0-10 numerical rating score) divided by the participant's concurrent physical activity level (measured as the average number of activity counts per minute via actigraphy). All fatigability scores will be averaged over the 7 days to create an aggregate fatigability score. Higher scores indicate greater fatigability. Change in fatigability between baseline and 12 weeks will be compared between the 3 treatment groups."}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['cognitive behavioral therapy', 'modafinil', 'Provigil', 'fatigue', 'MS'], 'conditions': ['Multiple Sclerosis']}, 'referencesModule': {'references': [{'pmid': '16900749', 'type': 'BACKGROUND', 'citation': 'Krupp L. Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. Mult Scler. 2006 Aug;12(4):367-8. doi: 10.1191/135248506ms1373ed. No abstract available.'}, {'pmid': '17903208', 'type': 'BACKGROUND', 'citation': 'Lerdal A, Celius EG, Krupp L, Dahl AA. A prospective study of patterns of fatigue in multiple sclerosis. Eur J Neurol. 2007 Dec;14(12):1338-43. doi: 10.1111/j.1468-1331.2007.01974.x. Epub 2007 Sep 26.'}, {'pmid': '12409184', 'type': 'BACKGROUND', 'citation': 'Janardhan V, Bakshi R. Quality of life in patients with multiple sclerosis: the impact of fatigue and depression. J Neurol Sci. 2002 Dec 15;205(1):51-8. doi: 10.1016/s0022-510x(02)00312-x.'}, {'pmid': '3355400', 'type': 'BACKGROUND', 'citation': 'Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol. 1988 Apr;45(4):435-7. doi: 10.1001/archneur.1988.00520280085020.'}, {'pmid': '16193900', 'type': 'BACKGROUND', 'citation': 'Smith MM, Arnett PA. Factors related to employment status changes in individuals with multiple sclerosis. Mult Scler. 2005 Oct;11(5):602-9. doi: 10.1191/1352458505ms1204oa.'}, {'pmid': '8180914', 'type': 'BACKGROUND', 'citation': 'Fisk JD, Pontefract A, Ritvo PG, Archibald CJ, Murray TJ. The impact of fatigue on patients with multiple sclerosis. Can J Neurol Sci. 1994 Feb;21(1):9-14.'}, {'pmid': '8148458', 'type': 'BACKGROUND', 'citation': 'Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. doi: 10.1093/clinids/18.supplement_1.s79.'}, {'pmid': '2803071', 'type': 'BACKGROUND', 'citation': 'Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.'}, {'pmid': '14583691', 'type': 'BACKGROUND', 'citation': 'Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov;41(11):1284-92. doi: 10.1097/01.MLR.0000093487.78664.3C.'}, {'pmid': '11556941', 'type': 'BACKGROUND', 'citation': 'Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.'}, {'pmid': '39424559', 'type': 'DERIVED', 'citation': 'Braley TJ, Ehde DM, Alschuler KN, Little R, Ng YT, Zhai Y, von Geldern G, Chervin RD, Conroy D, Valentine TR, Romeo AR, LaRocca N, Hamade M, Jordan A, Singh M, Segal BM, Kratz AL. Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial. Lancet Neurol. 2024 Nov;23(11):1108-1118. doi: 10.1016/S1474-4422(24)00354-5.'}]}, 'descriptionModule': {'briefSummary': 'This clinical trial will compare the effectiveness of 3 treatments for fatigue in Multiple Sclerosis: 1) a commonly used behavioral treatment strategy (telephone-based cognitive behavioral therapy), 2) a commonly used medication (modafinil), and 3) a combination of both therapies. Each participant will receive one of these 3 treatments for a total of 12 weeks. Hypotheses are that, at 12 weeks, treatment with combination therapy will overall lead to greater reductions in fatigue impact, fatigue severity, and fatigability compared to monotherapy, and that comorbid depression, sleep disturbances, and baseline disability level will be important effect modifiers that influence treatment effect and adherence.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Patients with clinically definite Multiple Sclerosis (MS, all MS subtypes);\n2. Age 18 years or older;\n3. Presence of chronic, problematic fatigue that, in the opinion of the patient, has interfered with their daily activities for ≥ 3 months;\n4. Average Fatigue Severity Scale (FSS) score greater or equal to 4 at screening.\n\nExclusion Criteria:\n\n1. Current shift work sleep disorder, or narcolepsy diagnosed with polysomnography and multiple sleep latency test\n2. History of MS relapse within the last 30 days prior to screening (participants will be considered eligible after the 30-day window);\n3. Current stimulant or wake-promoting agent use (such as amantadine, modafinil, methylphenidate, or amphetamine) within 30 days of screening;\n4. Pregnancy or breastfeeding;\n5. Reliance on hormonal contraception AND concomitant unwillingness to use alternative non-hormonal means of birth control (spermicide or condoms) during the course of the study;\n6. Current suicidal ideation (SI) with intent or plan;\n7. Known hypersensitivity to modafinil or armodafinil or its inactive ingredients;\n8. History of the following cardiovascular conditions: recent myocardial infarction (last 6 months prior to screening), unstable angina, left ventricular hypertrophy, mitral valve prolapse, NYHA class III or IV congestive heart failure;\n9. History of prescription or illicit stimulant abuse (such as cocaine, amphetamine, methamphetamine);\n10. Any other medical, neurological, or psychiatric condition that, in the opinion of the investigators, could affect participant safety or eligibility.'}, 'identificationModule': {'nctId': 'NCT03621761', 'acronym': 'COMBO-MS', 'briefTitle': 'Cognitive Behavioral Therapy, Modafinil, or Both for Multiple Sclerosis Fatigue', 'organization': {'class': 'OTHER', 'fullName': 'University of Michigan'}, 'officialTitle': 'A Randomized Controlled Trial of Telephone-delivered Cognitive Behavioral-therapy, Modafinil, and Combination Therapy of Both Interventions for Fatigue in Multiple Sclerosis', 'orgStudyIdInfo': {'id': 'HUM00143319'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Cognitive Behavioral Therapy', 'description': '8 weekly telephone-based sessions and 2 booster sessions', 'interventionNames': ['Behavioral: Telephone-based Cognitive Behavioral Therapy']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Modafinil', 'description': '50-400 mg per day (oral)', 'interventionNames': ['Drug: Modafinil']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Cognitive Behavioral Therapy + Modafinil', 'description': 'Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)', 'interventionNames': ['Behavioral: Telephone-based Cognitive Behavioral Therapy', 'Drug: Modafinil']}], 'interventions': [{'name': 'Telephone-based Cognitive Behavioral Therapy', 'type': 'BEHAVIORAL', 'description': 'Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.', 'armGroupLabels': ['Cognitive Behavioral Therapy', 'Cognitive Behavioral Therapy + Modafinil']}, {'name': 'Modafinil', 'type': 'DRUG', 'otherNames': ['Provigil'], 'description': 'Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).', 'armGroupLabels': ['Cognitive Behavioral Therapy + Modafinil', 'Modafinil']}]}, 'contactsLocationsModule': {'locations': [{'zip': '48109', 'city': 'Ann Arbor', 'state': 'Michigan', 'country': 'United States', 'facility': 'The University of Michigan', 'geoPoint': {'lat': 42.27756, 'lon': -83.74088}}, {'zip': '98195', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'facility': 'The University of Washington', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}], 'overallOfficials': [{'name': 'Tiffany J Braley, MD, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Michigan'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Michigan', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Washington', 'class': 'OTHER'}, {'name': 'Patient-Centered Outcomes Research Institute', 'class': 'OTHER'}, {'name': 'National Multiple Sclerosis Society', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Neurology', 'investigatorFullName': 'Tiffany J. Braley, MD, MS', 'investigatorAffiliation': 'University of Michigan'}}}}