Ignite Creation Date:
2025-12-25 @ 5:01 AM
Ignite Modification Date:
2026-01-26 @ 9:25 PM
Study NCT ID:
NCT01171118
Status:
COMPLETED
Last Update Posted:
2015-04-27
First Post:
2010-07-26
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Phamacological Reversal of Airway Instability During Sedation
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000402', 'term': 'Airway Obstruction'}, {'id': 'D053120', 'term': 'Respiratory Aspiration'}], 'ancestors': [{'id': 'D012131', 'term': 'Respiratory Insufficiency'}, {'id': 'D012120', 'term': 'Respiration Disorders'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D010830', 'term': 'Physostigmine'}, {'id': 'C026718', 'term': 'physostigmine salicylate'}, {'id': 'D010100', 'term': 'Oxygen'}, {'id': 'D000077330', 'term': 'Saline Solution'}], 'ancestors': [{'id': 'D048448', 'term': 'Phenylcarbamates'}, {'id': 'D002219', 'term': 'Carbamates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D026121', 'term': 'Indole Alkaloids'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D054836', 'term': 'Indolizidines'}, {'id': 'D007212', 'term': 'Indolizines'}, {'id': 'D018011', 'term': 'Chalcogens'}, {'id': 'D004602', 'term': 'Elements'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D005740', 'term': 'Gases'}, {'id': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'suzanne_karan@urmc.rochester.edu', 'phone': '585-275-5161', 'title': 'Dr. Suzanne Karan', 'organization': 'University of Rochester'}, 'certainAgreement': {'piSponsorEmployee': True}, 'limitationsAndCaveats': {'description': 'Study done on healthy non OSA male patients. Has to be confirmed with patients suffering from moderate to severe OSA.'}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Physostigmine', 'description': 'Physostigmine (PS), a centrally-acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the post-anesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep disordered breathing.We investigated whether PS was effective in decreasing the frequency of ventilatory arrhythmias (VA) produced during moderate sedation with midazolam and remifentanil in both room air (RA) and 2 l/m nasal O2. Midazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuously Capsaicin : 0.075% topical cream application', 'otherNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.', 'otherNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Oxygen', 'description': 'Subjects were assessed for two separate one hour periods of time -- one hour while breathing oxygen via a nasal cannula at 2 liters/minute', 'otherNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Room Air', 'description': 'Subjects were assessed for two separate one hour periods of time -- one hour while breathing room air', 'otherNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'AHI - Apnea Hypopnea Index', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}, {'value': '10', 'groupId': 'OG003'}]}], 'groups': [{'id': 'OG000', 'title': 'Physostigmine/Oxygen', 'description': 'Physostigmine (PS), a centrally-acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the post-anesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep disordered breathing.We investigated whether PS was effective in decreasing the frequency of ventilatory arrhythmias (VA) produced during moderate sedation with midazolam and remifentanil in both room air (RA) and 2 l/m nasal O2. Midazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuously Capsaicin : 0.075% topical cream application Subjects were breathing oxygen via nasal cannula at 2 liters/minute'}, {'id': 'OG001', 'title': 'Placebo/Oxygen', 'description': 'Physostigmine (PS), a centrally-acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the post-anesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep disordered breathing.We investigated whether PS was effective in decreasing the frequency of ventilatory arrhythmias (VA) produced during moderate sedation with midazolam and remifentanil in both room air (RA) and 2 l/m nasal O2. Midazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuously Capsaicin : 0.075% topical cream application Subjects were breathing oxygen via nasal cannula at 2 liters/minute'}, {'id': 'OG002', 'title': 'Physostigmine/Room Air', 'description': 'Each subject received the sedation protocol as described below:\n\nMidazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuously Then, subjects were randomized to the specific order of each four arms. Subjects breathed room air and received placebo instead of physostigimine in this arm.'}, {'id': 'OG003', 'title': 'Placebo/Room Air', 'description': 'Each subject received the sedation protocol as described below:\n\nMidazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuously Then, subjects were randomized to the specific order of each four arms. Subjects breathed room air and received placebo instead of physostigimine in this arm.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.5', 'spread': '21.7', 'groupId': 'OG000'}, {'value': '27.9', 'spread': '49.3', 'groupId': 'OG001'}, {'value': '11.3', 'spread': '19.4', 'groupId': 'OG002'}, {'value': '12.1', 'spread': '21.1', 'groupId': 'OG003'}]}]}], 'paramType': 'MEAN', 'timeFrame': '2- 2 1/2 hours during study visit', 'description': 'This is a standard metric used to describe severity of disordered breathing during sleep.Normal healthy subjects would have an AHI value of zero during sleep. Mild disordered breathing would correspond to a value of 5 to 10 events per hours; moderate 10-25; severe would be over 25', 'unitOfMeasure': 'events per hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'This is a standard size for this type of sleep study and was performed per protocol.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Physostigmine vs. Placebo in Room Air vs. O2 During Sedation', 'description': 'Each subject received the sedation protocol as described below:\n\nMidazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuously Then, subjects were randomized to the specific order of each four arms. Physostigmine (PS) vs. Placebo were randomized by DAYS. Then, on each day, subjects were randomized to receive oxygen or room air first or second. But each subject went through BOTH days and both oxygen and room air on each day.\n\nThere were eight total possible sequences.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Dates of recruitment August 2009 to December 2010. Subjects were recruited from advertisements.', 'preAssignmentDetails': 'Subjects excluded from trial before assignment to group because BMI to high, medication exclusions, lost of follow up, scheduling conflict.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Physostigmine/Placebo', 'description': 'Physostigmine (PS), a centrally-acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the post-anesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep disordered breathing.We investigated whether PS was effective in decreasing the frequency of ventilatory arrhythmias (VA) produced during moderate sedation with midazolam and remifentanil in both room air (RA) and 2 l/m nasal O2. Midazolam : The sedation will be initated with a midazolam infusion with an effect-site target of 100 mg/ml intraventously Remifentanil : 0.3 mg/ml intravenously continuouslyCapsaicin : 0.075% topical cream applicationPlacebo:We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this.'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '24.7', 'spread': '5.7', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': '10 subjects were studied in a crossover format but each subject completed all arms of the study.'}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-08'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-04', 'completionDateStruct': {'date': '2011-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-04-24', 'studyFirstSubmitDate': '2010-07-26', 'resultsFirstSubmitDate': '2013-03-08', 'studyFirstSubmitQcDate': '2010-07-27', 'lastUpdatePostDateStruct': {'date': '2015-04-27', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2015-04-24', 'studyFirstPostDateStruct': {'date': '2010-07-28', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-04-27', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'AHI - Apnea Hypopnea Index', 'timeFrame': '2- 2 1/2 hours during study visit', 'description': 'This is a standard metric used to describe severity of disordered breathing during sleep.Normal healthy subjects would have an AHI value of zero during sleep. Mild disordered breathing would correspond to a value of 5 to 10 events per hours; moderate 10-25; severe would be over 25'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Breathing', 'Sedation'], 'conditions': ['Upper Airway Obstruction']}, 'descriptionModule': {'briefSummary': 'The investigators are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias(central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in Obstructed Sleep Apnea (OSA) patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study in physostigmine versus placebo.', 'detailedDescription': 'One of the most serious side effects of drugs administered for sedation is untoward respiratory events. The relative prevalence of such events is thought to be high, occurring in up to 41% of patients in some cohorts. Many specific drugs and combinations have been recommended for moderate sedation, particularly when provided by a non-anesthesiologist. The use of an opioid and a benzodiazepine is the most frequent combination, partly because the availability of antagonists for both drugs may make a "rescue" easier. However, this combination results in frequent respiratory arrhythmias (combinations of obstructions, pauses and changes in respiratory patterns).There has not been a comprehensive study of the mechanisms underlying the disruptions of respiratory rhythm caused by agents commonly used for moderate sedation. This specific research, and the line of research it opens, has the potential to make the administration of anxiolytics and analgesics safer for patients at high risk for respiratory events.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Ages 18-45\n* BMI below 25\n* Healthy males\n\nExclusion Criteria:\n\n* Psychiatric illness\n* Substance abuse\n* Airway disorders\n* Bleeding abnormatlities\n* Claustrophobia\n* Sleep apnea.'}, 'identificationModule': {'nctId': 'NCT01171118', 'acronym': 'PHYSO', 'briefTitle': 'Phamacological Reversal of Airway Instability During Sedation', 'organization': {'class': 'OTHER', 'fullName': 'University of Rochester'}, 'officialTitle': 'Phamacological Reversal of Airway Instability During Sedation', 'orgStudyIdInfo': {'id': '17789'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sedation & Physostigmine & Room Air', 'description': 'We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.', 'interventionNames': ['Drug: Physostigmine']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Sedation & Placebo & Room Air', 'description': 'We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Sedation & Physostigmine & Oxygen', 'description': 'We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.', 'interventionNames': ['Drug: Physostigmine', 'Drug: Oxygen']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Sedation & Placebo & Oxygen', 'description': 'We are attempting to demonstrate a decrease in the frequency and severity of sedation-induced respiratory arrhythmias (central and obstructive apneas) with pharmacological pre-treatment in this pilot project and then eventually to understand the mechanisms behind this decrease. The efficacy and mechanisms of these treatments, while evaluated during sleep in OSA patients, have not been systematically studied during sedation in either normal subjects or OSA patients. The agent to be assessed in this study is physostigmine versus placebo.We are interested in the effect of breathing oxygen vs. room air on the regulation of respiratory control during moderate sedation.', 'interventionNames': ['Drug: Oxygen', 'Drug: Placebo']}], 'interventions': [{'name': 'Physostigmine', 'type': 'DRUG', 'otherNames': ['Antilirium'], 'description': 'Physostigmine is a centrally acting acetylcholinesterase inhibitor that has been proposed as a treatment for sleep disordered breathing. It is currently FDA approved and used commonly by Anesthesiologists in the post anesthetic setting to reverse confusion caused by central anticholinergic medication effects.', 'armGroupLabels': ['Sedation & Physostigmine & Oxygen', 'Sedation & Physostigmine & Room Air']}, {'name': 'Oxygen', 'type': 'DRUG', 'description': 'The administration of nasal cannula-administered oxygen at a flow rate of 2 liters/minute is commonly performed during clinical sedation practice. Thus, this experiment employed its use to compare respiratory effects of oxygen versus room air.', 'armGroupLabels': ['Sedation & Physostigmine & Oxygen', 'Sedation & Placebo & Oxygen']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Normal Saline'], 'description': 'The administration of placebo versus physostigmine was untertaken in the same sedation conditions on the alternate day in each subject (and with both room air and oxygen)', 'armGroupLabels': ['Sedation & Placebo & Oxygen', 'Sedation & Placebo & Room Air']}]}, 'contactsLocationsModule': {'locations': [{'zip': '14642', 'city': 'Rochester', 'state': 'New York', 'country': 'United States', 'facility': 'University of Rochester Medical Center', 'geoPoint': {'lat': 43.15478, 'lon': -77.61556}}], 'overallOfficials': [{'name': 'Suzanne B Karan, Medical', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Rochester'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Rochester', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal investigator', 'investigatorFullName': 'Suzanne Karan', 'investigatorAffiliation': 'University of Rochester'}}}}