Ignite Creation Date:
2025-12-24 @ 10:09 PM
Ignite Modification Date:
2026-03-29 @ 4:34 PM
Study NCT ID:
NCT02685735
Status:
TERMINATED
Last Update Posted:
2025-08-15
First Post:
2015-06-01
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Predicting, Understanding and Speeding Recovery After TKA
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010146', 'term': 'Pain'}], 'ancestors': [{'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077206', 'term': 'Gabapentin'}, {'id': 'D005079', 'term': 'Excipients'}], 'ancestors': [{'id': 'D000588', 'term': 'Amines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D005680', 'term': 'gamma-Aminobutyric Acid'}, {'id': 'D000613', 'term': 'Aminobutyrates'}, {'id': 'D002087', 'term': 'Butyrates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D003509', 'term': 'Cyclohexanecarboxylic Acids'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}, {'id': 'D003510', 'term': 'Cyclohexanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D014677', 'term': 'Pharmaceutical Vehicles'}, {'id': 'D010592', 'term': 'Pharmaceutic Aids'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D020313', 'term': 'Specialty Uses of Chemicals'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'jimeisenach@gmail.com', 'phone': '336-716-4182', 'title': 'Dr. James Eisenach', 'organization': 'Wake Forest University School of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Early termination leading to 240 rather than 250 participants analyzed.'}}, 'adverseEventsModule': {'timeFrame': 'through study completion, an average of 1 year per participant', 'description': 'Adverse events related to known effects of gabapentin (sedation, dizziness, nausea) were assessed daily via the daily digital diaries beginning two weeks prior to surgery (the time study drug began) and continuing for 3 weeks after surgery, when study drug was discontinued. Adverse events during hospitalization were captured via the electronic medical health record. Other adverse events were captured daily via digital diaries until 2 months after surgery, then at 6- and 12- month phone calls.', 'eventGroups': [{'id': 'EG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.', 'otherNumAtRisk': 135, 'deathsNumAtRisk': 135, 'otherNumAffected': 17, 'seriousNumAtRisk': 135, 'deathsNumAffected': 1, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.', 'otherNumAtRisk': 139, 'deathsNumAtRisk': 139, 'otherNumAffected': 2, 'seriousNumAtRisk': 139, 'deathsNumAffected': 1, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Somnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 135, 'numEvents': 10, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 139, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (10.0)'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 135, 'numEvents': 7, 'numAffected': 7}, {'groupId': 'EG001', 'numAtRisk': 139, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (10.0)'}], 'seriousEvents': [{'term': 'Death', 'notes': 'The participant was found dead at home on the morning of surgery. Because of a history of several serious cardiac disorders, the presumptive cause of death was cardiac arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 135, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 139, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (10.0)'}], 'frequencyThreshold': '3'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo--Intercept', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '123', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.57', 'groupId': 'OG000', 'lowerLimit': '7.17', 'upperLimit': '7.88'}, {'value': '7.52', 'groupId': 'OG001', 'lowerLimit': '7.16', 'upperLimit': '7.88'}]}]}], 'analyses': [{'pValue': '0.882', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value not adjusted for multiple comparisons, with threshold of statistical significance set at \\<0.05', 'groupDescription': 'The estimates were conducted using a linear mixed effects model contrasting differences in the gabapentin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, age, sex, pupil diameter, and catastophizing-optimism construct.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY', 'nonInferiorityComment': 'A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without gabapentin treatment group. A statistically significant result is interpreted as evidence to support that the gabapentin treatment impacts some element of change after surgery (i.e, intercept or slope).'}], 'paramType': 'MEAN', 'timeFrame': 'The first day after hospital discharge up to 5 days post surgery', 'description': 'Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for gabapentin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.\n\nValues represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.', 'unitOfMeasure': 'score on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The intention-to-treat population included all randomized patients who had at least one baseline pupil measurement, received at least one dose of study drug, and provided at least one pain score after the day of surgery.'}, {'type': 'SECONDARY', 'title': 'Wisconsin Card Sort Task', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}, {'value': '116', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'classes': [{'title': 'Preoperative', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000', 'lowerLimit': '-8', 'upperLimit': '20'}, {'value': '2', 'groupId': 'OG001', 'lowerLimit': '-10', 'upperLimit': '24'}]}]}, {'title': '2 months after surgery', 'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000', 'lowerLimit': '-4', 'upperLimit': '42'}, {'value': '8', 'groupId': 'OG001', 'lowerLimit': '-10', 'upperLimit': '40'}]}]}, {'title': '6 months after surgery', 'categories': [{'measurements': [{'value': '18', 'groupId': 'OG000', 'lowerLimit': '-4', 'upperLimit': '45'}, {'value': '18', 'groupId': 'OG001', 'lowerLimit': '-2', 'upperLimit': '41'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Preoperative, 2 months after surgery, 6 months after surgery', 'description': 'This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The total completed for this secondary outcome is 113 in the gabapentin group and 116 in the placebo group. The reason for not completing was failure to complete questionnaires on at least one of the three occasions that these were performed.'}, {'type': 'SECONDARY', 'title': 'Iowa Gambling Task', 'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'OG000'}, {'value': '115', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'classes': [{'title': 'Preoperative', 'categories': [{'measurements': [{'value': '8', 'groupId': 'OG000', 'lowerLimit': '5', 'upperLimit': '14'}, {'value': '7', 'groupId': 'OG001', 'lowerLimit': '5', 'upperLimit': '10'}]}]}, {'title': '2 months after surgery', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000', 'lowerLimit': '4', 'upperLimit': '10'}, {'value': '6', 'groupId': 'OG001', 'lowerLimit': '4', 'upperLimit': '10'}]}]}, {'title': '6 months after surgery', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000', 'lowerLimit': '4', 'upperLimit': '8'}, {'value': '5', 'groupId': 'OG001', 'lowerLimit': '4', 'upperLimit': '8'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Preoperative, 2 months after surgery, 6 months after surgery', 'description': 'This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The total completed for this secondary outcome is 111 in the gabapentin group and 115 in the placebo group. The reason for not completing was failure to complete the task on at least one of the three occasions that these were performed.'}, {'type': 'SECONDARY', 'title': 'Tampa Scale of Kinesiophobia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}, {'value': '117', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'classes': [{'title': 'Preoperative', 'categories': [{'measurements': [{'value': '37', 'groupId': 'OG000', 'lowerLimit': '33', 'upperLimit': '41'}, {'value': '38', 'groupId': 'OG001', 'lowerLimit': '35', 'upperLimit': '41'}]}]}, {'title': '2 months after surgery', 'categories': [{'measurements': [{'value': '36', 'groupId': 'OG000', 'lowerLimit': '33', 'upperLimit': '39'}, {'value': '37', 'groupId': 'OG001', 'lowerLimit': '34', 'upperLimit': '40'}]}]}, {'title': '6 months after surgery', 'categories': [{'measurements': [{'value': '37', 'groupId': 'OG000', 'lowerLimit': '34', 'upperLimit': '40'}, {'value': '36', 'groupId': 'OG001', 'lowerLimit': '34', 'upperLimit': '40'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Preoperative, 2 months after surgery, 6 months after surgery', 'description': 'This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'The total completed for secondary analyses is 113 in the gabapentin group and 117 in the placebo group. The reason for not completing was failure to complete questionnaires on at least one of the three occasions that these were performed.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Biomarkers of Stress', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will be randomized, stratifying for norepinephrine serotonin reuptake inhibitor (NSRI) use, to equal number to receive gabapentin or placebo pills. Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.\n\nGabapentin: Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will be randomized, stratifying for norepinephrine serotonin reuptake inhibitor (NSRI) use, to equal number to receive gabapentin or placebo pills. Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.\n\nPlacebo: Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.'}], 'timeFrame': 'Preoperative', 'description': 'Blood and cerebrospinal fluid will be obtained and frozen for subsequent assessment of hormones, neurochemicals, and other secreted compounds indicative of stress. Analysis will be in the future and dependent upon new literature for ideal biomarkers.', 'reportingStatus': 'POSTED', 'populationDescription': 'Data were not collected'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Biomarkers of Noradrenergic Functioning', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'timeFrame': 'Preoperative', 'description': 'Blood and cerebrospinal fluid will be obtained and frozen for subsequent assessment of compounds reflecting noradrenergic functioning. Analysis will be in the future and dependent upon new literature for ideal biomarkers.', 'reportingStatus': 'POSTED', 'populationDescription': 'Data were not collected'}, {'type': 'PRIMARY', 'title': 'Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo-- Slope', 'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'OG000'}, {'value': '123', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.110', 'groupId': 'OG000', 'lowerLimit': '-0.113', 'upperLimit': '-0.107'}, {'value': '-0.114', 'groupId': 'OG001', 'lowerLimit': '-0.117', 'upperLimit': '-0.111'}]}]}], 'analyses': [{'pValue': '0.137', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P value not adjusted for multiple comparisons, with threshold of statistical significance set at \\<0.05', 'groupDescription': 'The estimates were conducted using a linear mixed effects model contrasting differences in the gabapentin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline pain, age, sex, pupil diameter, and catastrophizing-optimism construct.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY', 'nonInferiorityComment': 'A likelihood-ratio test for change in pain was conducted for each outcome comparing a model with and without gabapentin treatment group. A statistically significant result is interpreted as evidence to support that the gabapentin treatment impacts some element of change after surgery (i.e, intercept or slope).'}], 'paramType': 'MEAN', 'timeFrame': 'Postoperative Day 1 through Postoperative Day 60', 'description': 'Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for gabapentin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.\n\nSlope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.', 'unitOfMeasure': 'score on a scale/ln(day)', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The intention-to-treat population included all randomized patients who had at least one baseline pupil measurement, received at least one dose of study drug, and provided at least one pain score after the day of surgery.'}, {'type': 'PRIMARY', 'title': 'Effect Pupil Diameter, Catastrophizing-optimism Construct, and Gabapentin on Model Fit of the Trajectory of Change in Worst Daily Pain After Surgery', 'denoms': [{'units': 'Participants', 'counts': [{'value': '240', 'groupId': 'OG000'}, {'value': '240', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Adjusted Daily Worst Pain Trajectory Model (Model 1)', 'description': 'Pain scores over time were fit to a ln(time) change model, including pre-defined prognostic covariates (age, sex, surgery site, and study site). This model considered each predictor and its interaction with the ln(time).'}, {'id': 'OG001', 'title': 'Pain Trajectory Model Plus Pupil, Cognitive Style, and Study Drug Factors (Model 2)', 'description': 'A full model that used all of the predictors from Model 1 with the addition of the catastrophizing-optimism cognitive construct (Cats-Opt), the baseline pupil diameter (Pupil), and randomized study drug group assignment (Group). As in Model 1, this model considered each predictor and its interaction with the ln(time). The two-way and three-way interactions among these variables were also specified alone and in conjunction with ln(time).'}], 'classes': [{'categories': [{'measurements': [{'value': '43604', 'groupId': 'OG000'}, {'value': '343523', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.0001', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'The null hypothesis (H0) is that modeled trajectory of change in pain intensity report after total hip or total knee arthroplasty does not differ between oral gabapentin and placebo in a manner dependent on its interaction with preferred cognitive style and pre-surgery pupil resting diameter . The alternative hypothesis (H1) is that there is a difference between the two groups which is dependent on these interactions.', 'statisticalMethod': 'Chi-squared', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': '14 degrees of freedom', 'otherAnalysisDescription': 'A likelihood ratio test was conducted to compare these two models, conditional on the difference in the degrees of freedom in both models. A statistically significant likelihood ratio test would be interpreted as evidence that the three mechanistic predictors (Catastrophising-Optimism construct, Study Group, resting Pupil diameter) impact some aspect of the change in pain that occurs after surgery. If a statistically significant effect is observed, the individual interaction parameters will be interpreted.'}], 'paramType': 'NUMBER', 'timeFrame': 'Postoperative Day 1 through Postoperative Day 60', 'description': 'Daily pain intensity report for each subject was fitted using growth curve model, adjusted for pre-specified prognostic predictors . The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.\n\nDeviance values were calculated from the model fit with just pre-specified prognostic predictors (Model 1) and the model fit with these predictors plus pupil diameter, catastrophizing-optimism construct, gabapentin treatment and their interaction. Deviance is a goodness-of-fit statistic for a statistical model; it is often used for statistical hypothesis testing. It is a generalization of the idea of using the sum of squares of residuals (SSR) in ordinary least squares to cases where model-fitting is achieved by maximum likelihood. Deviance ranges from 0 to infinity. The smaller the number the better the model fits the sample data.\n\nModel fits were compared using Chi-squared test.', 'unitOfMeasure': 'unitless', 'reportingStatus': 'POSTED', 'populationDescription': 'The intention-to-treat population included all randomized patients who had at least one baseline pupil measurement, received at least one dose of study drug, and provided at least one pain score after the day of surgery. The primary analysis, as pre-specified in the statistical analysis plan and upon which sample size was determined, tested whether growth curve model for change in pain over 2 months was better fit when group, pupil diameter, and cognitive construct scores were added.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '135'}, {'groupId': 'FG001', 'numSubjects': '139'}]}, {'type': 'COMPLETED', 'comment': 'These subjects completed and provide data for the primary analysis. The total completed for secondary analyses is 89 in the gabapentin group and 93 in the placebo group. The reason for not completing was failure to complete questionnaires on at least one of the three occasions that these were performed.', 'achievements': [{'groupId': 'FG000', 'numSubjects': '117'}, {'groupId': 'FG001', 'numSubjects': '123'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}, {'groupId': 'FG001', 'numSubjects': '16'}]}], 'dropWithdraws': [{'type': 'Surgery Cancelled', 'reasons': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Preop testing found to be incomplete', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Enrollment occurred from June 2, 2016 to August 2, 2021 at the Orthopeadic Clinics of Atrium Wake Forest Baptist and Davie County facilities and May 9, 2017 to July 21, 2020 at Cleveland Clinic facilities. Change in clinical practice resulted in inability to recruit subjects on high doses of opioid preoperatively, so recruitment of 50 subject in Aim 3 which was intended to separately examine interactions in this population did not occur.', 'preAssignmentDetails': 'Enrollment occurred greater or equal to 2 weeks prior to surgery. A total of 76 individuals were excluded prior to assignment to groups during the period prior to surgery because of cancellation of the planned surgery.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '117', 'groupId': 'BG000'}, {'value': '123', 'groupId': 'BG001'}, {'value': '240', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Gabapentin', 'description': 'Subjects will receive gabapentin, 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Subjects will receive placebo pills and the number of pills will be the same as gabapentin in the active treatment arm. Treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '60.8', 'spread': '7.8', 'groupId': 'BG000'}, {'value': '60.7', 'spread': '9.1', 'groupId': 'BG001'}, {'value': '60.8', 'spread': '8.5', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '60', 'groupId': 'BG000'}, {'value': '71', 'groupId': 'BG001'}, {'value': '131', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '57', 'groupId': 'BG000'}, {'value': '52', 'groupId': 'BG001'}, {'value': '109', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '116', 'groupId': 'BG000'}, {'value': '121', 'groupId': 'BG001'}, {'value': '237', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '18', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '33', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '98', 'groupId': 'BG000'}, {'value': '107', 'groupId': 'BG001'}, {'value': '205', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '117', 'groupId': 'BG000'}, {'value': '123', 'groupId': 'BG001'}, {'value': '240', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Worst daily pain', 'classes': [{'categories': [{'measurements': [{'value': '4.78', 'spread': '2.77', 'groupId': 'BG000'}, {'value': '4.71', 'spread': '2.31', 'groupId': 'BG001'}, {'value': '4.75', 'spread': '2.54', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'From daily diaries completed for 2 weeks prior to surgery in which the participant rated each day the worst pain in the past 24 hours with 0=no pain and 10=worst pain imaginable', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Resting pupil diameter', 'classes': [{'categories': [{'measurements': [{'value': '6.1', 'spread': '1.9', 'groupId': 'BG000'}, {'value': '5.9', 'spread': '1.8', 'groupId': 'BG001'}, {'value': '6.0', 'spread': '1.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Pupil diameter measured using infrared video recording at rest in a constant, low ambient light, low ambient noise room and in the absence of stimulation', 'unitOfMeasure': 'mm', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Optimism/acceptance of pain to catastrophizing cognitive style', 'classes': [{'categories': [{'measurements': [{'value': '-0.12', 'spread': '1.0', 'groupId': 'BG000'}, {'value': '0.00', 'spread': '1.08', 'groupId': 'BG001'}, {'value': '0.00', 'spread': '1.0', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'A unidimensional scale that represents a broader spectrum of cognitive style that ranges from optimism/acceptance of pain to catastrophizing, derived from the Life Orientation Test-R (LOT-R) and catastrophizing to pain (CATS) questionnaires. Values of the derived scale are presented as theta, approximately equivalent to a z-score, with a range of -3 to 3 with negative numbers indicating optimism and positive numbers indicating catastrophizing.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2020-03-05', 'size': 889629, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_004.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2025-07-31T13:16', 'hasProtocol': True}, {'date': '2023-04-26', 'size': 530116, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_003.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2023-05-03T08:52', 'hasProtocol': False}, {'date': '2020-12-14', 'size': 208305, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_002.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2022-08-05T13:22', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 350}}, 'statusModule': {'whyStopped': 'lack of continued funding support', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2016-06-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-05', 'completionDateStruct': {'date': '2022-02-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-08-01', 'studyFirstSubmitDate': '2015-06-01', 'resultsFirstSubmitDate': '2023-03-09', 'studyFirstSubmitQcDate': '2016-02-15', 'lastUpdatePostDateStruct': {'date': '2025-08-15', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2023-10-03', 'studyFirstPostDateStruct': {'date': '2016-02-19', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2023-10-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-02-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Biomarkers of Stress', 'timeFrame': 'Preoperative', 'description': 'Blood and cerebrospinal fluid will be obtained and frozen for subsequent assessment of hormones, neurochemicals, and other secreted compounds indicative of stress. Analysis will be in the future and dependent upon new literature for ideal biomarkers.'}, {'measure': 'Biomarkers of Noradrenergic Functioning', 'timeFrame': 'Preoperative', 'description': 'Blood and cerebrospinal fluid will be obtained and frozen for subsequent assessment of compounds reflecting noradrenergic functioning. Analysis will be in the future and dependent upon new literature for ideal biomarkers.'}], 'primaryOutcomes': [{'measure': 'Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo--Intercept', 'timeFrame': 'The first day after hospital discharge up to 5 days post surgery', 'description': 'Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for gabapentin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.\n\nValues represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.'}, {'measure': 'Comparison of Adjusted Trajectory Model for Pain Between Gabapentin and Placebo-- Slope', 'timeFrame': 'Postoperative Day 1 through Postoperative Day 60', 'description': 'Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for gabapentin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.\n\nSlope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.'}, {'measure': 'Effect Pupil Diameter, Catastrophizing-optimism Construct, and Gabapentin on Model Fit of the Trajectory of Change in Worst Daily Pain After Surgery', 'timeFrame': 'Postoperative Day 1 through Postoperative Day 60', 'description': 'Daily pain intensity report for each subject was fitted using growth curve model, adjusted for pre-specified prognostic predictors . The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain.\n\nDeviance values were calculated from the model fit with just pre-specified prognostic predictors (Model 1) and the model fit with these predictors plus pupil diameter, catastrophizing-optimism construct, gabapentin treatment and their interaction. Deviance is a goodness-of-fit statistic for a statistical model; it is often used for statistical hypothesis testing. It is a generalization of the idea of using the sum of squares of residuals (SSR) in ordinary least squares to cases where model-fitting is achieved by maximum likelihood. Deviance ranges from 0 to infinity. The smaller the number the better the model fits the sample data.\n\nModel fits were compared using Chi-squared test.'}], 'secondaryOutcomes': [{'measure': 'Wisconsin Card Sort Task', 'timeFrame': 'Preoperative, 2 months after surgery, 6 months after surgery', 'description': 'This is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.'}, {'measure': 'Iowa Gambling Task', 'timeFrame': 'Preoperative, 2 months after surgery, 6 months after surgery', 'description': 'This is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity'}, {'measure': 'Tampa Scale of Kinesiophobia', 'timeFrame': 'Preoperative, 2 months after surgery, 6 months after surgery', 'description': 'This 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Pain', 'Total Knee Replacement', 'Total Hip Replacement']}, 'descriptionModule': {'briefSummary': 'The objective of this research study is to better understand patterns of recovery after Total Knee Arthroplasty (TKA) amd Total Hip Replacement (THA). The study will evaluate how pain, activity and cognitive (i.e., thinking style) responses determine patterns of recovery, and the study will evaluate the efficacy of gabapentin versus placebo for improving recovery after surgery.', 'detailedDescription': 'The investigators propose a two-site, longitudinal, double-blind, randomized clinical intervention study to examine three specific aims:\n\nAim 1: Characterize the dynamic pain experience, activity, and cognitive response after TKA and determine patterns of recovery in these domains\n\nAim 2: Test whether gabapentin alters time course of recovery after TKA or THA in a manner dependent on its interaction with pre-drug pupil diameter and preferred style in the catastrophizing-optimism dimension\n\nAim 3: Test whether gabapentin increases pupil diameter in patients undergoing TKA or THA who are on high dose opioids preoperatively and to examine whether opioid use moderates the associations in Aim 1\n\nPrimary Hypothesis: Novel variance beyond established associations in recovery from pain following TKA or THA surgery is accounted for by the interaction between pupil diameter and Cognitive-Affective (C-A) state, and this interaction predicts efficacy of gabapentin to speed recovery.\n\nKey secondary hypotheses: Disability, impulsivity, and attentional deficits recover after TKA or THA surgery follow a log of time pattern, and are predicted by C-A state and its interaction with pupil diameter. Gabapentin increases resting pupil diameter in patients scheduled for TKA who are receiving high doses of opioids.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Adults scheduled for elective total knee or hip replacement\n* American Society of Anesthesiologists physical status 1-3\n* Participants must be able to read and write English\n\nExclusion Criteria:\n\n* Inability to complete questionnaires\n* Pregnancy\n* Litigation or workers compensation related to joint surgery\n* For 250 subjects in primary analysis - taking \\< 100 mg morphine equivalents/day. For 50 subjects to test gabapentin's effect on pupil diameter - taking \\>100 mg morphine equivalents/day\n* history of Raynaud's disease of the feet\n* suffering from a psychotic disorder or a recent psychiatric hospitalization\n* history of eye surgery or topical eye medications that would render pupillometry unreliable or would directly affect pupil diameter.\n* any disorder that would affect pupil responsivity or prevent accuracy of pupillometry such as movement disorders"}, 'identificationModule': {'nctId': 'NCT02685735', 'briefTitle': 'Predicting, Understanding and Speeding Recovery After TKA', 'organization': {'class': 'OTHER', 'fullName': 'Wake Forest University Health Sciences'}, 'officialTitle': 'Predicting, Understanding, and Speeding Recovery After Total Knee Arthroplasty', 'orgStudyIdInfo': {'id': 'IRB00032506'}, 'secondaryIdInfos': [{'id': '5P01GM113852', 'link': 'https://reporter.nih.gov/quickSearch/5P01GM113852', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Gabapentin', 'description': 'Subjects will be randomized, stratifying for norepinephrine serotonin reuptake inhibitor (NSRI) use, to equal number to receive gabapentin or placebo pills. Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.', 'interventionNames': ['Drug: Gabapentin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Subjects will be randomized, stratifying for norepinephrine serotonin reuptake inhibitor (NSRI) use, to equal number to receive gabapentin or placebo pills. Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Gabapentin', 'type': 'DRUG', 'otherNames': ['neurontin'], 'description': 'Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.', 'armGroupLabels': ['Gabapentin']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Inert ingredient'], 'description': 'Drug treatment will begin 2 weeks prior to surgery and continue 3 weeks afterwards. Subjects randomized to gabapentin will receive 900 mg/day for the first week, 1800 mg/day for the next 3 weeks, and 900 mg/day for the last week.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '27157', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest Baptist Medical Center', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}], 'overallOfficials': [{'name': 'James C Eisenach, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Wake Forest University Health Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Wake Forest University Health Sciences', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of General Medical Sciences (NIGMS)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}