Ignite Creation Date:
2025-12-25 @ 4:26 AM
Ignite Modification Date:
2026-03-02 @ 4:11 AM
Study NCT ID:
NCT01557920
Status:
COMPLETED
Last Update Posted:
2016-09-13
First Post:
2012-03-15
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001049', 'term': 'Apnea'}, {'id': 'D006935', 'term': 'Hypercapnia'}], 'ancestors': [{'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D012818', 'term': 'Signs and Symptoms, Respiratory'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015742', 'term': 'Propofol'}, {'id': 'D000077149', 'term': 'Sevoflurane'}], 'ancestors': [{'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D008738', 'term': 'Methyl Ethers'}, {'id': 'D004987', 'term': 'Ethers'}, {'id': 'D006845', 'term': 'Hydrocarbons, Fluorinated'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'meikermann@partners.org', 'phone': '6176434408', 'title': 'Dr. Matthias Eikermann', 'organization': 'Massachusetts General Hospital'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Propofol', 'description': 'The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nPropofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.', 'otherNumAtRisk': 12, 'otherNumAffected': 0, 'seriousNumAtRisk': 12, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Sevoflurane', 'description': 'The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nSevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.', 'otherNumAtRisk': 12, 'otherNumAffected': 0, 'seriousNumAtRisk': 12, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Upper Airway Closing Pressure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Propofol', 'description': 'The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nPropofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.'}, {'id': 'OG001', 'title': 'Sevoflurane', 'description': 'The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nSevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.'}], 'classes': [{'categories': [{'measurements': [{'value': '-9.83', 'spread': '3.92', 'groupId': 'OG000'}, {'value': '-10.77', 'spread': '4.69', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'participants will be followed for the duration of anesthesia, an expected average of 6 hours', 'description': 'Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.', 'unitOfMeasure': 'cm H20', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Ten out of 12 subjects were analyzed. In two subjects we could not record high quality biologically plausible recordings of upper airway closing pressure. Data from multiple measurements per participant were combined to calculate an average upper airway closing pressure per subject.'}, {'type': 'PRIMARY', 'title': 'Proportion of Pathological Swallows', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}, {'value': '11', 'groupId': 'OG003'}, {'value': '11', 'groupId': 'OG004'}, {'value': '11', 'groupId': 'OG005'}]}], 'groups': [{'id': 'OG000', 'title': 'Anesthesia With Propofol and Sevoflurane (All Cases)', 'description': 'Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (across carbon-dioxide (CO2) levels).'}, {'id': 'OG001', 'title': 'Wakefulness (All Cases)', 'description': 'Proportion of pathological (inspiratory) swallows during wakefulness (across CO2 levels)'}, {'id': 'OG002', 'title': 'Anesthesia With Propofol and Sevoflurane (Baseline CO2)', 'description': 'Proportion of pathological (inspiratory) swallows during anesthesia with propofol and sevoflurane (during baseline CO2).'}, {'id': 'OG003', 'title': 'Anesthesia With Propofol and Sevoflurane (CO2 Insufflation)', 'description': 'Proportion of pathological (inspiratory) swallows during anesthesia (with CO2+4 and +8 insufflation).'}, {'id': 'OG004', 'title': 'Wakefulness (During Baseline CO2)', 'description': 'Proportion of pathological (inspiratory) swallows during anesthesia (during baseline CO2).'}, {'id': 'OG005', 'title': 'Wakefulness (With CO2 Insufflation)', 'description': 'Proportion of pathological (inspiratory) swallows during wakefulness (with CO2+4 and +8 insufflation).'}], 'classes': [{'categories': [{'measurements': [{'value': '25.9', 'groupId': 'OG000'}, {'value': '4.9', 'groupId': 'OG001'}, {'value': '15.8', 'groupId': 'OG002'}, {'value': '34.9', 'groupId': 'OG003'}, {'value': '1.0', 'groupId': 'OG004'}, {'value': '13.2', 'groupId': 'OG005'}]}]}], 'analyses': [{'pValue': '0.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'pathological swallows under anesthesia vs. wakefulness: 25.9% vs. 4.9%', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}, {'pValue': '<0.001', 'groupIds': ['OG002', 'OG003', 'OG004', 'OG005'], 'groupDescription': 'Comparison of pathological swallow-rate increase by carbon-dioxide during anesthesia and wakefulness', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'NUMBER', 'timeFrame': 'swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)', 'description': 'A pathological swallow was defined as a swallow that was followed by inspiratory flow. A physiological swallow was defined as a swallow that was followed by expiratory flow. The number of pathological and physiological swallows were measured during wakefulness and anesthesia. The pathological swallows are presented as percentage of path. swallows calculated as path.sw/\\[path.sw+phys.sw\\]\\*100 (%).', 'unitOfMeasure': 'percentage of pathological swallows', 'reportingStatus': 'POSTED', 'populationDescription': '224 swallows in 11 out of 12 subjects were analyzed (1 excluded due to faulty recording of swallows).'}, {'type': 'SECONDARY', 'title': 'Airway Diameter', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}, {'value': '0', 'groupId': 'OG002'}, {'value': '0', 'groupId': 'OG003'}, {'value': '0', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Wakefulness'}, {'id': 'OG001', 'title': 'Anesthesia With Low Dose Sevoflurane (Baseline CO2)'}, {'id': 'OG002', 'title': 'Anesthesia With High Dose Sevoflurane (Baseline CO2)'}, {'id': 'OG003', 'title': 'Anesthesia With Low Dose Propofol (CO2 Baseline)'}, {'id': 'OG004', 'title': 'Anesthesia With High Dose Propofol (CO2 Baseline)'}], 'timeFrame': 'participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours', 'description': 'Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.', 'reportingStatus': 'POSTED', 'populationDescription': 'No data were obtained.'}, {'type': 'SECONDARY', 'title': 'Genioglossus Muscle Electromyogram', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '9', 'groupId': 'OG001'}, {'value': '9', 'groupId': 'OG002'}, {'value': '9', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Phasic Genioglossus Activity (Light Anesthesia)', 'description': 'Phasic activity (Peak activity - Tonic activity)'}, {'id': 'OG001', 'title': 'Tonic Genioglossus Activity (Light Anesthesia)', 'description': 'Tonic Genioglossus activity (light anesthesia)'}, {'id': 'OG002', 'title': 'Phasic Genioglossus Activity (Deep Anesthesia)', 'description': 'Phasic activity (Peak activity - Tonic activity)'}, {'id': 'OG003', 'title': 'Tonic Genioglossus Activity (Deep Anesthesia)', 'description': 'Tonic Genioglossus activity (deep anesthesia)'}], 'classes': [{'categories': [{'measurements': [{'value': '32.8', 'spread': '2.1', 'groupId': 'OG000'}, {'value': '24.2', 'spread': '1.8', 'groupId': 'OG001'}, {'value': '26.0', 'spread': '1.8', 'groupId': 'OG002'}, {'value': '22.3', 'spread': '2.0', 'groupId': 'OG003'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours', 'description': 'will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.', 'unitOfMeasure': 'percentage of maximum recorded activity', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'The number of participants in this group are only 9 since the genioglossus EMG signals were poor in 2 participants and these were excluded from the analysis.'}, {'type': 'SECONDARY', 'title': 'Minute Ventilation (Tidal Volume and Respiratory Rate)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}, {'value': '11', 'groupId': 'OG003'}, {'value': '11', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Wakefulness', 'description': 'Minute Ventilation (CO2 baseline)'}, {'id': 'OG001', 'title': 'Anesthesia With Low Dose Sevoflurane (Baseline CO2)', 'description': 'Minute ventilation during anesthesia with sevoflurane (during baseline CO2).'}, {'id': 'OG002', 'title': 'Anesthesia With High Dose Sevoflurane (Baseline CO2)', 'description': 'Minute ventilation during anesthesia with sevoflurane (baseline CO2)'}, {'id': 'OG003', 'title': 'Anesthesia With Low Dose Propofol (CO2 Baseline)', 'description': 'Minute Ventilation during anesthesia with propofol (CO2 baseline).'}, {'id': 'OG004', 'title': 'Anesthesia With High Dose Propofol (CO2 Baseline)', 'description': 'Minute Ventilation during anesthesia with propofol (during baseline CO2).'}], 'classes': [{'categories': [{'measurements': [{'value': '7.9', 'spread': '1.7', 'groupId': 'OG000'}, {'value': '6.7', 'spread': '1.3', 'groupId': 'OG001'}, {'value': '5.6', 'spread': '1.5', 'groupId': 'OG002'}, {'value': '7.2', 'spread': '1.7', 'groupId': 'OG003'}, {'value': '5.7', 'spread': '1.3', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours', 'description': 'Measured by spirometry. Subjects wear a full-face mask. Reported in L/min', 'unitOfMeasure': 'L/min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'In one subject we could not record high quality biologically plausible recordings of minute ventilation.'}, {'type': 'SECONDARY', 'title': 'Duty Cycle', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}, {'value': '11', 'groupId': 'OG002'}, {'value': '11', 'groupId': 'OG003'}, {'value': '11', 'groupId': 'OG004'}]}], 'groups': [{'id': 'OG000', 'title': 'Wakefulness', 'description': 'Duty cycle (CO2 baseline)'}, {'id': 'OG001', 'title': 'Anesthesia With Low Dose Sevoflurane (Baseline CO2)', 'description': 'Duty cycle during anesthesia with sevoflurane (during baseline CO2).'}, {'id': 'OG002', 'title': 'Anesthesia With High Dose Sevoflurane (Baseline CO2)', 'description': 'Duty cycle during anesthesia with sevoflurane (baseline CO2)'}, {'id': 'OG003', 'title': 'Anesthesia With Low Dose Propofol (CO2 Baseline)', 'description': 'Duty cycle during anesthesia with propofol (CO2 baseline).'}, {'id': 'OG004', 'title': 'Anesthesia With High Dose Propofol (CO2 Baseline)', 'description': 'Duty cycle during anesthesia with propofol (during baseline CO2).'}], 'classes': [{'categories': [{'measurements': [{'value': '42', 'spread': '3', 'groupId': 'OG000'}, {'value': '42', 'spread': '5', 'groupId': 'OG001'}, {'value': '43', 'spread': '4', 'groupId': 'OG002'}, {'value': '40', 'spread': '3', 'groupId': 'OG003'}, {'value': '41', 'spread': '3', 'groupId': 'OG004'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours', 'description': '(T(ins)/T(total))\\*100', 'unitOfMeasure': 'percentage of Ttotal', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'In one subject we could not record high quality biologically plausible recordings of Duty cycle.'}, {'type': 'POST_HOC', 'title': 'Frequency of Spontaneous Swallows During Anesthesia vs Wakefulness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Anesthesia With Propofol and Sevoflurane'}, {'id': 'OG001', 'title': 'Wakefulness'}], 'classes': [{'categories': [{'measurements': [{'value': '1.7', 'spread': '3.3', 'groupId': 'OG000'}, {'value': '28', 'spread': '22.3', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'pValueComment': 'The number of swallows per hour: 1.7±3.3 during anesthesia vs. 28.0±22.3 during wakefulness', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)', 'description': 'The number of swallows were counted during wakefulness and anesthesia. The frequency of swallowing was calculated per hour', 'unitOfMeasure': 'number of swallows/hr', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '224 swallows in 11 out of 12 subjects were analyzed (1 excluded due to faulty recording of swallows). If the pathological swallow incidence between sevoflurane and propofol anesthesia had a p-value \\>0.05, subsequent analyses were conducted to evaluate depth of anesthesia related differences rather than compound specific ones.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Propofol First, Then Sevoflurane', 'description': 'The healthy subject will be anesthetized first with Propofol, and secondarily with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nPropofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.\n\nSevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.'}, {'id': 'FG001', 'title': 'Sevoflurane First, Then Propofol', 'description': 'The healthy subject will be anesthetized first with Sevoflurane, and secondarily with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nPropofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.\n\nSevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '9'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Lack of Efficacy', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Crossover Randomized Propofol and Sevoflurane', 'description': 'The healthy subject will be anesthetized with Propofol and Sevoflurane in a randomized crossover fashion. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline.\n\nSpontaneous swallows were identified, and categorized as physiological or pathological. Physiological swallows were followed by expiratory flow (E or I-E). Pathological swallows were followed by inspiration (I and E-I).\n\nPropofol: Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.\n\nSevoflurane: Sevoflurane will be administered via mask inhalation to achieve anesthesia.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '24.3', 'spread': '3.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '11', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '18', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['PARTICIPANT']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-08', 'completionDateStruct': {'date': '2014-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-08-01', 'studyFirstSubmitDate': '2012-03-15', 'resultsFirstSubmitDate': '2015-04-12', 'studyFirstSubmitQcDate': '2012-03-16', 'lastUpdatePostDateStruct': {'date': '2016-09-13', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2016-03-21', 'studyFirstPostDateStruct': {'date': '2012-03-20', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-04-21', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Upper Airway Closing Pressure', 'timeFrame': 'participants will be followed for the duration of anesthesia, an expected average of 6 hours', 'description': 'Upper airway closing pressure will be measured during steady state anesthesia as well as during carbon dioxide reversal.'}, {'measure': 'Proportion of Pathological Swallows', 'timeFrame': 'swallows were measured during steady state conditions (mean±SEM, 2.6±0.6h)', 'description': 'A pathological swallow was defined as a swallow that was followed by inspiratory flow. A physiological swallow was defined as a swallow that was followed by expiratory flow. The number of pathological and physiological swallows were measured during wakefulness and anesthesia. The pathological swallows are presented as percentage of path. swallows calculated as path.sw/\\[path.sw+phys.sw\\]\\*100 (%).'}], 'secondaryOutcomes': [{'measure': 'Airway Diameter', 'timeFrame': 'participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours', 'description': 'Using acoustic pharyngometry, we intend to measure the cross-sectional area of the airway at several points during recovery from anesthesia.'}, {'measure': 'Genioglossus Muscle Electromyogram', 'timeFrame': 'participants will be followed for the duration of anesthesia until full recovery, an expected average of 9 hours', 'description': 'will be measured during steady state anesthesia as well as during carbon dioxide reversal, and during recovery from anesthesia.'}, {'measure': 'Minute Ventilation (Tidal Volume and Respiratory Rate)', 'timeFrame': 'Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours', 'description': 'Measured by spirometry. Subjects wear a full-face mask. Reported in L/min'}, {'measure': 'Duty Cycle', 'timeFrame': 'Will be measured before and during anesthesia until emergence from anesthesia, an expected average of 6 hours', 'description': '(T(ins)/T(total))\\*100'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['apnea', 'airway collapsibility', 'healthy', 'hypercapnia', 'general anesthesia', 'breathing-swallow coordination', 'aspiration'], 'conditions': ['Airway Complication of Anaesthesia', 'Healthy']}, 'referencesModule': {'references': [{'pmid': '18431126', 'type': 'BACKGROUND', 'citation': 'Eikermann M, Malhotra A, Fassbender P, Zaremba S, Jordan AS, Gautam S, White DP, Chamberlin NL. Differential effects of isoflurane and propofol on upper airway dilator muscle activity and breathing. Anesthesiology. 2008 May;108(5):897-906. doi: 10.1097/ALN.0b013e31816c8a60.'}, {'pmid': '22108392', 'type': 'BACKGROUND', 'citation': 'Eikermann M, Grosse-Sundrup M, Zaremba S, Henry ME, Bittner EA, Hoffmann U, Chamberlin NL. Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology. 2012 Jan;116(1):35-46. doi: 10.1097/ALN.0b013e31823d010a.'}, {'pmid': '20032012', 'type': 'BACKGROUND', 'citation': 'Eikermann M, Eckert DJ, Chamberlin NL, Jordan AS, Zaremba S, Smith S, Rosow C, Malhotra A. Effects of pentobarbital on upper airway patency during sleep. Eur Respir J. 2010 Sep;36(3):569-76. doi: 10.1183/09031936.00153809. Epub 2009 Dec 23.'}]}, 'descriptionModule': {'briefSummary': 'The investigators hypothesize that propofol, when compared to sevoflurane, causes the upper airway to collapse more easily and causes less activity in the tongue muscle. Additionally, the investigators hypothesize that, under increased carbon dioxide concentrations of the air inhaled, the upper airway will be less likely to collapse under anesthesia and there will be increased activity in the tongue muscle under both propofol and sevoflurane, when compared to breathing normal concentrations of carbon dioxide, as in room air. Furthermore the investigators hypothesize that anesthesia disrupt the breathing swallow coordination, an effect additionally altered by increased carbon dioxide through increased respiratory drive.', 'detailedDescription': 'Upper airway patency depends on an appropriate balance between the dilating force of pharyngeal muscles and the collapsing force of negative intraluminal pressure, which is generated by respiratory "pump" muscles. The genioglossus (GG) protects pharyngeal patency in humans. This muscle receives various types of neural drive, distributed differentially across the hypoglossal motoneuron pool, including phasic (inspiratory) and tonic (non-respiratory) drives. In addition, reflex GG activation in response to negative pharyngeal pressure stabilizes upper airway patency both in humans and in rats. General anesthetic agents, including propofol and sevoflurane, predispose the upper airway to collapse, at least in part by decreasing upper airway muscle activity.\n\nTheoretically anesthetics could affect upper airway dilator activity by several mechanisms, including an anesthetic-induced, dose-dependent decrease in hypercapnic and hypoxic ventilatory drive, hypoglossal motoneuron depression, decreased skeletal muscle contractility, an increase in phasic GG activity as a result of decreased arterial blood pressure, and an increase in phasic hypoglossal nerve discharge.\n\nPrevious studies have shown that certain anesthetics, including pentobarbital and isoflurane, can increase genioglossus phasic activity in rats and in humans. The effects of propofol on airway collapsibility have been studied in humans however, to our knowledge, they have not been measured under conditions of hypercapnia. Studies of airway collapsibility under sevoflurane anesthesia have been performed in children, but no data exists for airway collapsibility in sevoflurane-anesthetized adults. Similarly no data exists on the effects of sevoflurane on GG activity\n\nIn a previous trial of pentobarbital-anesthetized volunteers, the investigators observed that mild hypercapnia (5 - 10 mmHg above baseline) produced a significant increase in flow rate and GG phasic activity, as well as a smaller increase in GG tonic activity. If our proposed study shows a beneficial effect, then the investigators plan a follow-up study addressing the possibility that hypercapnia may be used therapeutically for airway protection. A similar concept has already been considered for critically ill ICU patients.\n\nHowever, previous studies have shown that a hypercapnia-induced increase in ventilatory drive can inhibit airway protective reflexes by disrupting the breathing swallowing coordination. In order to assess the safety of induced mild hypercapnia as an intervention for airway protection, we evaluated whether variable levels of hypercapnia occurring during anesthesia with sevoflurane and propofol impair the coordination of breathing and swallowing compared with the effects of anesthesia alone.\n\nWith this pharmaco-physiological interaction study on healthy adults we aim to:\n\n1. Compare the effects of sevoflurane and propofol on upper airway closing pressure, upper airway muscle control and breathing.\n2. Assess the effects of evoked hypercapnia (carbon dioxide reversal) on propofol-induced upper airway collapsibility\n3. Evaluate the effects of sevoflurane, propofol, and induced hypercapnia on coordination of breathing and swallowing.\n\nComparative drug studies on airway effects of anesthetics in humans are important for defining an optimal anesthetic regimen for patients at risk of airway collapse, such as patients with obstructive sleep apnea. Our studies are also particularly relevant for patients undergoing procedural sedation, which is typically being conducted under spontaneous ventilation with the upper airway being unprotected. In addition, our results may increase our understanding of postoperative airway obstruction, a common complication in the post-anesthesia recovery room.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* American Society of Anesthesiologists (ASA) class I\n* Age between 18 and 45\n* BMI 18-28 kg/m\\^2\n\nExclusion Criteria:\n\n* Concurrent significant medical illness (heart disease including untreated hypertension, Clinically significant kidney disease, liver disease, or lung disease, History of myasthenia gravis or other muscle and nerve disease)\n* Anxiety disorder requiring treatment\n* Concurrent medications known to affect anesthesia, upper airway muscles or respiratory function (e.g., gabaergic anxiolytics, antipsychotics)\n* Individuals with a history of allergy or adverse reaction to lidocaine, propofol, or sevoflurane\n* For women: pregnancy\n* Suggestion of obstructive sleep apnea (OSA) or any other sleep disorder (e.g. witnessed apneas, gasping or choking during sleep, unexplained excessive daytime sleepiness)\n* History of drug or alcohol abuse\n* Acute intermittent porphyria'}, 'identificationModule': {'nctId': 'NCT01557920', 'briefTitle': 'The Effects of General Anesthetics on Upper Airway Collapsibility in Healthy Subjects', 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts General Hospital'}, 'officialTitle': "The Effects of Sevoflurane, Propofol, and Carbon Dioxide 'Reversal' on Upper Airway Collapsibility in Healthy, Adult Subjects", 'orgStudyIdInfo': {'id': '2011P002472'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Propofol', 'description': 'The healthy subject will be anesthetized with Propofol. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline. Assessment of swallow patterns during anesthesia and wakefulness, as well as under differential CO2 levels will be assessed offline after recovery from anesthesia.', 'interventionNames': ['Drug: Propofol']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Sevoflurane', 'description': 'The healthy subject will be anesthetized with Sevoflurane. Respiratory measurements will be taken while the subject is anesthetized to calculate the airway closing pressure. After recovery from anesthesia, airway diameter and duty cycle will also be measured. In addition to breathing air mixture, subject will be given carbon dioxide to achieve end tidal CO2 levels of 4 mm and 8 mm above baseline. All respiratory measurements will be repeated at each level above baseline. Assessment of swallow patterns during anesthesia and wakefulness, as well as under differential CO2 levels will be assessed offline after recovery from anesthesia.', 'interventionNames': ['Drug: Sevoflurane']}], 'interventions': [{'name': 'Propofol', 'type': 'DRUG', 'description': 'Propofol administration for induction of general anesthesia. Administration will be performed IV, using a Target Controlled Induction Pump.', 'armGroupLabels': ['Propofol']}, {'name': 'Sevoflurane', 'type': 'DRUG', 'description': 'Sevoflurane will be administered via mask inhalation to achieve anesthesia.', 'armGroupLabels': ['Sevoflurane']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Matthias Eikermann, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Massachusetts General Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts General Hospital', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Director of Research, Surgical Intensive Care Unit', 'investigatorFullName': 'Matthias Eikermann', 'investigatorAffiliation': 'Massachusetts General Hospital'}}}}