Ignite Creation Date:
2025-12-25 @ 5:08 AM
Ignite Modification Date:
2025-12-26 @ 4:11 AM
Study NCT ID:
NCT01394627
Status:
COMPLETED
Last Update Posted:
2017-11-17
First Post:
2011-07-11
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Hypoglycemia and the Mineralocorticoid Receptor
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007003', 'term': 'Hypoglycemia'}], 'ancestors': [{'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077545', 'term': 'Eplerenone'}], 'ancestors': [{'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'gadler@partners.org', 'phone': '617-732-5661', 'title': 'Gail Adler', 'organization': "Brigham and Women's Hospital"}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Eplerenone', 'description': 'hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose) Eplerenone: 100mg x 2', 'otherNumAtRisk': 20, 'deathsNumAtRisk': 20, 'otherNumAffected': 0, 'seriousNumAtRisk': 20, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'hypoglycemia of 50 mg/dl plus placebo Placebo', 'otherNumAtRisk': 20, 'deathsNumAtRisk': 20, 'otherNumAffected': 0, 'seriousNumAtRisk': 20, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline in Cardiovascular Autonomic Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Eplerenone', 'description': 'hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose)\n\nEplerenone: 100mg x 2'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'hypoglycemia of 50 mg/dl plus placebo\n\nPlacebo'}], 'classes': [{'categories': [{'measurements': [{'value': '-16.00', 'spread': '18.39', 'groupId': 'OG000'}, {'value': '-16.59', 'spread': '16.77', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 2 hours after hypoglycemia', 'description': 'Modified oxford procedures was performed in duplicate immediately prior to start of the hypoglycemic clamp and during the last 30 min of the clamp (i.e. during the last 30 min of exposure to 2 hours of hypoglycemia).. We calculated the baroreflex sensitivity (the relationship between RR interval and change in systolic blood pressure defined as the change in the inter-beat cardiac interval in milliseconds per unit change in blood pressure in mmHg) at each time point and then the change in baroreflex sensitivity (BRS during hypoglycemia minus BRS at baseline)', 'unitOfMeasure': 'ms/mmHg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'We included the 13 subjects who completed each arm, had usable baroreflex sensitivity data for both treatments (placebo and eplerenone), and achieved a blood sugar during hypoglycemia of less than or equal to 3.0 mmol/L for each clamp.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Inflammation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '17', 'groupId': 'OG000'}, {'value': '17', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Eplerenone', 'description': 'hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose)\n\nEplerenone: 100mg x 2'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'hypoglycemia of 50 mg/dl plus placebo\n\nPlacebo'}], 'classes': [{'categories': [{'measurements': [{'value': '2.03', 'spread': '1.27', 'groupId': 'OG000'}, {'value': '2.61', 'spread': '2.63', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 2 hours after hypoglycemia', 'description': 'Change in interleukin-6', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'We included the 17 subjects who completed each arm and had interleukin-6 data for both arms (placebo and eplerenone). We calculated the change in IL-6 as IL-6 during hypoglycemia minus IL-6 at baseline.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo (Period 1) /Washout (Period 2)/Eplerenone (Period 3)', 'description': 'hypoglycemia of 50 mg/dl with 1 day of placebo pretreatment\n\nthen after 1-3 month washout\n\nhypoglycemia of 50 mg/dl with 1 day of eplerenone (100 mg x 2) pretreatment'}, {'id': 'FG001', 'title': 'Eplerenone (Period 1) /Washout (Period 2)/Placebo (Period 3)', 'description': 'hypoglycemia of 50 mg/dl with 1 day of eplerenone (100 mg x 2) pretreatment\n\nthen after 1-3 month washout\n\nhypoglycemia of 50 mg/dl with 1 day of placebo pretreatment'}], 'periods': [{'title': 'First Intervention (1 Day)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '13'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'poor intravenous access', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}, {'title': 'Washout (1-3 Months)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'concurrent enrollment in another study', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Second Intervention (1 Day)', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '21', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'All Participants'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '21', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '26.5', 'spread': '5.6', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '16', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '19', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '21', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 21}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-10', 'completionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-10-16', 'studyFirstSubmitDate': '2011-07-11', 'resultsFirstSubmitDate': '2017-07-14', 'studyFirstSubmitQcDate': '2011-07-13', 'lastUpdatePostDateStruct': {'date': '2017-11-17', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-10-16', 'studyFirstPostDateStruct': {'date': '2011-07-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-11-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline in Cardiovascular Autonomic Function', 'timeFrame': 'Baseline and 2 hours after hypoglycemia', 'description': 'Modified oxford procedures was performed in duplicate immediately prior to start of the hypoglycemic clamp and during the last 30 min of the clamp (i.e. during the last 30 min of exposure to 2 hours of hypoglycemia).. We calculated the baroreflex sensitivity (the relationship between RR interval and change in systolic blood pressure defined as the change in the inter-beat cardiac interval in milliseconds per unit change in blood pressure in mmHg) at each time point and then the change in baroreflex sensitivity (BRS during hypoglycemia minus BRS at baseline)'}], 'secondaryOutcomes': [{'measure': 'Change From Baseline in Inflammation', 'timeFrame': 'Baseline and 2 hours after hypoglycemia', 'description': 'Change in interleukin-6'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Hypoglycemia']}, 'referencesModule': {'references': [{'pmid': '26438610', 'type': 'RESULT', 'citation': 'Rao AD, Bonyhay I, Dankwa J, Baimas-George M, Kneen L, Ballatori S, Freeman R, Adler GK. Baroreflex Sensitivity Impairment During Hypoglycemia: Implications for Cardiovascular Control. Diabetes. 2016 Jan;65(1):209-15. doi: 10.2337/db15-0871. Epub 2015 Oct 5.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to look at whether blockade of the mineralocorticoid receptor will result in changes in the cardiovascular and inflammatory response to hypoglycemia.', 'detailedDescription': 'The effect of ongoing hypoglycemia on cardiovascular autonomic function is unclear and the focus of this protocol. In our preliminary studies, the investigators demonstrated that baroreflex sensitivity is impaired during hypoglycemia in healthy individuals. Treatment with eplerenone (200mg total administered in two doses in the 15 hours prior to the hypoglycemic clamp) prevented this impairment.\n\nThe study is based on the overarching hypothesis that hypoglycemia leads to increases in aldosterone/mineralocorticoid receptor (MR) activity and increased cardiovascular injury.\n\nThis study will address the following Specific Aims:\n\nTo test the hypothesis that MR blockade will reduce the adverse effects of hypoglycemia on inflammation and on autonomic control of cardiovascular function.\n\nThe investigators will determine the effects of hypoglycemia (50 mg/dl for 2.0 hours) on the blood inflammatory factor interleukin-6 levels, and on cardiovascular autonomic function (baroreflex sensitivity) in each subject under two conditions - pretreatment with MR blockade (eplerenone) and pretreatment with placebo.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy volunteers\n* Males and females age 18 to 40 years\n\nExclusion Criteria:\n\n* Pregnancy\n* Lactation\n* Menopause\n* Any medical condition other than treated hypothyroidism.\n* Alcoholism\n* Active tobacco use\n* In all subjects, any individuals on oral, injected, inhaled or topical corticosteroids within the last year or oral contraceptives within the past 3 months will be excluded.\n* Use of medications other than physiological thyroxine replacement\n* Serum potassium \\>5.0 mmol/L\n* Estimated glomerular filtration rate \\< 60 mL/min'}, 'identificationModule': {'nctId': 'NCT01394627', 'acronym': 'HypoMR', 'briefTitle': 'Hypoglycemia and the Mineralocorticoid Receptor', 'organization': {'class': 'OTHER', 'fullName': "Brigham and Women's Hospital"}, 'officialTitle': 'Hypoglycemia and the Mineralocorticoid Receptor', 'orgStudyIdInfo': {'id': '2010P002054'}, 'secondaryIdInfos': [{'id': 'K24HL103845', 'link': 'https://reporter.nih.gov/quickSearch/K24HL103845', 'type': 'NIH'}, {'id': 'R01HL109634', 'link': 'https://reporter.nih.gov/quickSearch/R01HL109634', 'type': 'NIH'}, {'id': 'T32HL007609', 'link': 'https://reporter.nih.gov/quickSearch/T32HL007609', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Eplerenone', 'description': 'hypoglycemia (50 mg/dl) with pretreatment with two doses of eplerenone (100 mg of eplerenone per dose)', 'interventionNames': ['Drug: Eplerenone']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'placebo', 'description': 'hypoglycemia of 50 mg/dl plus placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Eplerenone', 'type': 'DRUG', 'description': '100mg x 2', 'armGroupLabels': ['Eplerenone']}, {'name': 'Placebo', 'type': 'DRUG', 'armGroupLabels': ['placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Brigham and Women's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Gail K Adler, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}, {'name': 'Gail K Adler, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Brigham and Women's Hospital", 'class': 'OTHER'}, 'collaborators': [{'name': 'Robert Wood Johnson Foundation', 'class': 'OTHER'}, {'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}, {'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'Gail Kurr Adler', 'investigatorAffiliation': "Brigham and Women's Hospital"}}}}