Ignite Creation Date:
2025-12-25 @ 2:11 AM
Ignite Modification Date:
2026-04-15 @ 12:23 PM
Study NCT ID:
NCT02656160
Status:
COMPLETED
Last Update Posted:
2017-08-15
First Post:
2016-01-12
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effect of Dalfampridine (4-AP) on Genioglossus Muscle Activity in Healthy Adults
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020181', 'term': 'Sleep Apnea, Obstructive'}], 'ancestors': [{'id': 'D012891', 'term': 'Sleep Apnea Syndromes'}, {'id': 'D001049', 'term': 'Apnea'}, {'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D020919', 'term': 'Sleep Disorders, Intrinsic'}, {'id': 'D020920', 'term': 'Dyssomnias'}, {'id': 'D012893', 'term': 'Sleep Wake Disorders'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015761', 'term': '4-Aminopyridine'}], 'ancestors': [{'id': 'D000631', 'term': 'Aminopyridines'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'awellman@rics.bwh.harvard.edu', 'title': 'Andrew Wellman, MD, PhD', 'organization': "Brigham and women's Hospital"}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '2 weeks', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Placebo: Placebo 3 hrs before sleep', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Dalfampridine', 'description': 'Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 1, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Headache', 'notes': 'Headache after 1 hour from administration of dalfampridine, spontaneously recovered after approximately 1.5 hours', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Placebo: Placebo 3 hrs before sleep'}, {'id': 'OG001', 'title': 'Dalfampridine', 'description': 'Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep'}], 'classes': [{'title': 'Tonic genioglossus activity during sleep', 'categories': [{'measurements': [{'value': '166', 'groupId': 'OG000', 'lowerLimit': '101', 'upperLimit': '333'}, {'value': '136', 'groupId': 'OG001', 'lowerLimit': '90', 'upperLimit': '576'}]}]}, {'title': 'Phasic genioglossus activity during sleep', 'categories': [{'measurements': [{'value': '245', 'groupId': 'OG000', 'lowerLimit': '88', 'upperLimit': '428'}, {'value': '163', 'groupId': 'OG001', 'lowerLimit': '109', 'upperLimit': '793'}]}]}], 'analyses': [{'pValue': '0.85', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P\\<0.05 considered statistically significant', 'groupDescription': 'tonic', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'OTHER'}, {'pValue': '0.322', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P\\<0.05 considered statistically significant', 'groupDescription': 'Phasic activity', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEDIAN', 'timeFrame': '1 night', 'description': 'The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns).', 'unitOfMeasure': 'percentage of wakefulness value', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Placebo: Placebo 3 hrs before sleep'}, {'id': 'OG001', 'title': 'Dalfampridine', 'description': 'Dalfampridine: Dalfampridine 10 mg extended release 3 hrs before sleep'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.23', 'groupId': 'OG000', 'lowerLimit': '-0.57', 'upperLimit': '-0.09'}, {'value': '-0.36', 'groupId': 'OG001', 'lowerLimit': '-1.06', 'upperLimit': '-0.1'}]}]}], 'analyses': [{'pValue': '0.42', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'P\\<0.05 considered statistically significant', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEDIAN', 'timeFrame': '1 night', 'description': 'Effect of dalfampridine on genioglossus muscle responsiveness to increased epiglottic pressure swings during sleep in healthy controls during NREM sleep. The variation of EMG GG is expressed here as % of maximal activation.', 'unitOfMeasure': '%max/cmH2O', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': '4-AP First, Placebo Second', 'description': '4-AP 10 mg administered 3 hours before normal sleep time on first study night, then a 1-week non-treatment period, then placebo-matching 4-AP administered 3 hours before normal sleep time on second study night.'}, {'id': 'FG001', 'title': 'Placebo First, 4-AP Second', 'description': 'Placebo-matching 4-AP administered 3 hours before normal sleep time on first study night, then a 1-week non-treatment period, then 4-AP administered 3 hours before normal sleep time on second study night.'}], 'periods': [{'title': 'First Study Night', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Second Study Night', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': '3 subjects did not return for the second study night', 'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Analyzed Participants', 'description': 'All participants who were randomized, completed both study nights, and were included in the analysis.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '28', 'groupId': 'BG000', 'lowerLimit': '25.3', 'upperLimit': '33.3'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 13}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-07', 'completionDateStruct': {'date': '2016-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-07-14', 'studyFirstSubmitDate': '2016-01-12', 'resultsFirstSubmitDate': '2017-03-29', 'studyFirstSubmitQcDate': '2016-01-12', 'lastUpdatePostDateStruct': {'date': '2017-08-15', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-05-09', 'studyFirstPostDateStruct': {'date': '2016-01-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-06-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Genioglossus Activity During Sleep Expressed as %Wakefulness Value (Before Drug/Placebo Administration).', 'timeFrame': '1 night', 'description': 'The EMG GG was quantified in arbitrary units derived from signal processing of the raw signal and as a percentage of wakefulness (%wake) for between-nights comparison of baseline sleep EMG GG activity. EMG GG analysis was performed on a breath-by-breath basis to identify a maximum value and a minimum value during inspiration and expiration, respectively (EMG GG peak and tonic). The difference between peak and tonic values was used to estimate respiratory related phasic activity. Wakefulness EMG GG values were obtained from a minimum of 10 epochs (30 s each) with the subject lying in the lateral position. Criteria for breath selection during wakefulness were (1) stable breathing (constant epiglottic pressure swings) and (2) absence of movement artifacts (i.e., swallowing, speech, yawns).'}], 'secondaryOutcomes': [{'measure': 'Change in EMG GG for cmH2O Change in Epiglottic Pressure. (GG%Max/cmH2O)', 'timeFrame': '1 night', 'description': 'Effect of dalfampridine on genioglossus muscle responsiveness to increased epiglottic pressure swings during sleep in healthy controls during NREM sleep. The variation of EMG GG is expressed here as % of maximal activation.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Sleep Apnea, Obstructive']}, 'referencesModule': {'references': [{'pmid': '28387543', 'type': 'DERIVED', 'citation': 'Taranto-Montemurro L, Sands SA, Azarbarzin A, Marques M, de Melo CM, Edwards BA, Eckert DJ, Messineo L, White DP, Wellman A. Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults. Ann Am Thorac Soc. 2017 Jul;14(7):1177-1183. doi: 10.1513/AnnalsATS.201701-006OC.'}]}, 'descriptionModule': {'briefSummary': 'In this protocol the investigators will test the effect of dalfampridine (a potassium channel blocker) on genioglossus muscle activity (EMG GG) during wakefulness and sleep in healthy control subjects.', 'detailedDescription': "Two overnight sleep studies, a placebo night and a drug night, will be performed approximately one week apart in random order. The placebo or drug will be administered 3 hours before lights out. At least 10 minutes of quiet wakefulness will be recorded to quantify the subject's awake EMG GG activity before the administration of placebo/dalfampridine.\n\nEMG GG activity will be measured again 10 mins before lights off and during stable NREM and REM sleep (free of arousals and other artifacts).\n\nDuring the second part of the night, the subjects will be connected to a modified continuous positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which can provide a wide range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure and measure change in EMG GG as a function of epiglottic pressure (muscle responsiveness)."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy control subjects\n\nExclusion Criteria:\n\n* Cardiovascular disease other than well controlled hypertension\n* History of seizures'}, 'identificationModule': {'nctId': 'NCT02656160', 'acronym': 'APIGLOSS', 'briefTitle': 'Effect of Dalfampridine (4-AP) on Genioglossus Muscle Activity in Healthy Adults', 'organization': {'class': 'OTHER', 'fullName': "Brigham and Women's Hospital"}, 'officialTitle': 'The Effect of Dalfampridine (4-aminopyridine) on Genioglossus Muscle Activity During Wakefulness and Sleep in Healthy Control Subjects', 'orgStudyIdInfo': {'id': 'BWH-2014P001033C'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'interventionNames': ['Drug: Placebo']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Dalfampridine', 'interventionNames': ['Drug: Dalfampridine']}], 'interventions': [{'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo 3 hrs before sleep', 'armGroupLabels': ['Placebo']}, {'name': 'Dalfampridine', 'type': 'DRUG', 'description': 'Dalfampridine 10 mg extended release 3 hrs before sleep', 'armGroupLabels': ['Dalfampridine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Sleep Disorders Research Program Brigham and Women's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Brigham and Women's Hospital", 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': "Director, Sleep Disordered Breathing Lab, Brigham and Women's Hospital", 'investigatorFullName': 'David Andrew Wellman', 'investigatorAffiliation': "Brigham and Women's Hospital"}}}}