Ignite Creation Date:
2025-12-24 @ 5:56 PM
Ignite Modification Date:
2026-01-23 @ 12:52 AM
Study NCT ID:
NCT02690168
Status:
COMPLETED
Last Update Posted:
2021-07-19
First Post:
2016-01-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy
Sponsor:
Organization:
Raw JSON
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'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '4 days', 'eventGroups': [{'id': 'EG000', 'title': 'Fasting', 'description': '72 hour fasting', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 4, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Achy legs', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'sinus congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percent Enrichment of Bicarbonate as Measured by Magnetic Resonance Spectroscopy (MRS)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Healthy Men', 'description': 'Fasting: 72 hour fasting'}], 'classes': [{'categories': [{'measurements': [{'value': '61.9', 'spread': '3.8', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.0053', 'groupIds': ['OG000'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': '80 hours', 'unitOfMeasure': '% enrichment', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Collected data from one participant were not considered valid due to an equipment malfunction'}, {'type': 'SECONDARY', 'title': 'Cerebral Metabolic Rate of Acetate Ascertained Through Mathematical Modeling of MRS Data', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Fasting', 'description': '72 hour fasting'}], 'classes': [{'categories': [{'measurements': [{'value': '71', 'spread': '15.0', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.477', 'groupIds': ['OG000'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': '80 hours', 'unitOfMeasure': 'micromol/g/min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Collected data from one participant were not considered valid due to an equipment malfunction'}, {'type': 'SECONDARY', 'title': 'Astroglial TCA Cycle Rate Ascertained Through Mathematical Modeling of MRS Data', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Fasting', 'description': '72 hour fasting'}], 'classes': [{'categories': [{'measurements': [{'value': '0.4', 'spread': '0.2', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.917', 'groupIds': ['OG000'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': '80 hours', 'unitOfMeasure': 'micromol/g/min', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Collected data from one participant were not considered valid due to an equipment malfunction'}, {'type': 'SECONDARY', 'title': 'Glucose Level', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Fasting', 'description': '72 hour fasting'}], 'classes': [{'categories': [{'measurements': [{'value': '71', 'spread': '4.9', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '72 hours', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Leptin Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Fasting', 'description': '72 hour fasting'}], 'classes': [{'categories': [{'measurements': [{'value': '5.2', 'spread': '1.2', 'groupId': 'OG000'}]}]}], 'analyses': [{'pValue': '0.53', 'groupIds': ['OG000'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'OTHER'}], 'paramType': 'MEAN', 'timeFrame': '72 hours', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Data from 3 participants was not available due to lack of blood volume during collections'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Fasting', 'description': '72 hour fasting'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Healthy Men', 'description': 'Fasting: 72 hour fasting'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '28.7', 'spread': '2.4', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Weight', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '76.1', 'spread': '13.7', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Body Mass Index', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '23.5', 'spread': '2.7', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m^2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Fasting glucose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '85.1', 'spread': '6.9', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': '% body fat', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '17.6', 'spread': '7.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': '% body fat', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Percent enrichment of bicarbonate', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '53.5', 'spread': '8.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': '% enrichment', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Collected data from one participant were not considered valid due to an equipment malfunction'}, {'title': 'Cerebral Metabolic Rate of Acetate Ascertained Through Mathematical Modeling of MRS Data', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '59', 'spread': '20.8', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'micromol/g/min', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Collected data from one participant were not considered valid due to an equipment malfunction'}, {'title': 'Astroglial tricarboxylic acid cycle rate ascertained through mathematical modeling of MRS data', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '0.5', 'spread': '0.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'micromol/g/min', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Collected data from one participant were not considered valid due to an equipment malfunction'}, {'title': 'Leptin', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '7.2', 'spread': '5.9', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'parameter could only be measured in 3 subject due to lack of collected blood volume'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2016-09-22', 'size': 650214, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-09-17T16:01', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Blood banking'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 6}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-06', 'completionDateStruct': {'date': '2017-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-06-28', 'studyFirstSubmitDate': '2016-01-27', 'resultsFirstSubmitDate': '2020-09-17', 'studyFirstSubmitQcDate': '2016-02-18', 'lastUpdatePostDateStruct': {'date': '2021-07-19', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-06-28', 'studyFirstPostDateStruct': {'date': '2016-02-24', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-07-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-03-27', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percent Enrichment of Bicarbonate as Measured by Magnetic Resonance Spectroscopy (MRS)', 'timeFrame': '80 hours'}], 'secondaryOutcomes': [{'measure': 'Cerebral Metabolic Rate of Acetate Ascertained Through Mathematical Modeling of MRS Data', 'timeFrame': '80 hours'}, {'measure': 'Astroglial TCA Cycle Rate Ascertained Through Mathematical Modeling of MRS Data', 'timeFrame': '80 hours'}, {'measure': 'Glucose Level', 'timeFrame': '72 hours'}, {'measure': 'Change in Leptin Levels', 'timeFrame': '72 hours'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Fasting', 'Carbon-13 Magnetic Resonance Spectroscopy', 'Neuroimaging'], 'conditions': ['Diabetes Complications', 'Hypoglycemia']}, 'referencesModule': {'references': [{'pmid': '29931424', 'type': 'DERIVED', 'citation': 'McDougal DH, Darpolor MM, DuVall MA, Sutton EF, Morrison CD, Gadde KM, Redman LM, Carmichael OT. Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia. Acta Diabetol. 2018 Oct;55(10):1029-1036. doi: 10.1007/s00592-018-1180-5. Epub 2018 Jun 22.'}]}, 'descriptionModule': {'briefSummary': 'Hypoglycemia-associated autonomic failure (HAAF), a condition commonly developed in diabetic patients, which causes them to have severely low blood sugar levels. This condition makes clinical management of blood sugar in diabetic patients very challenging. This research seeks to better understand how diabetic patients develop HAAF, and what can be done to prevent it.', 'detailedDescription': 'Following the detection of severe hypoglycemia by the central nervous system (CNS), a series of physiological countermeasures are triggered which return serum glucose to euglycemic levels. This vital homeostatic response frequently becomes dysfunctional in both type 1 and type 2 diabetics, leaving them particularly vulnerable to life threatening bouts of hypoglycemia. This dysfunction, often termed hypoglycemia-associated autonomic failure (HAAF), is thought to be caused by maladaptive changes in the CNS. Currently, progress towards rectifying this HAAF is severely hindered by a lack of knowledge regarding the exact nature of these maladaptive changes and the antecedent events which cause them. Previous work by the PI, as well as others, has identified altered glial metabolism as a potential biological substrate driving HAAF. The alterations in glial metabolism associated with HAAF are strikingly similar to those induced by prolonged dietary restriction in rodents. This raises the intriguing possibility that HAAF may be driven by glial adaptations, normally induced only by prolonged starvation, which are triggered in diabetic individuals by treatment-induced exposure to severe hypoglycemia. The primary goal of our pilot project is to conduct a prospective observational study in humans to test the hypothesis that prolonged fasting will induce changes in glial metabolism similar to those previously measured in individuals with HAAF. The investigators will accomplish this goal via the following specific aims: Aim 1: Using a prospective observational study design in humans, test whether a 72 hour fast will induce acute alterations in glial metabolism, Aim 2: Determine if changes in plasma glucose and leptin levels following prolonged fasting are correlated with changes in glial adaptation. The investigators will utilize innovative 13C magnetic resonance spectroscopy to measure alterations in glial metabolism and substrate preference following acute dietary restriction in healthy young individuals. By demonstrating that metabolic adaptations of glial cells induced by prolonged fasting are similar to those previously associated with HAAF, the investigators can provide key insights into the precursors that may lead to the development of HAAF in diabetic individuals.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Healthy Men', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male\n* BMI 20.0-24.9 kg/m2\n* 18-40 years old\n* Willing to reside at Pennington Biomedical for 4 days\n\nExclusion Criteria:\n\n* Type 1 diabetes mellitus\n* Type 2 diabetes mellitus\n* Fasting glucose ≥ 110 mg/dL (determined at screening visit)\n* Hyperketonuria \\>15 mg/dL, (determined at screening visit)\n* Contraindication to MRI\n* History of or current eating disorder\n* History of obsessive compulsive disorder\n* Current use of any medication (excluding over-the-counter pain medication)\n* Contraindication to prolonged fasting\n* Consume \\>10 alcoholic drinks/week'}, 'identificationModule': {'nctId': 'NCT02690168', 'acronym': 'GLIMpSE', 'briefTitle': 'Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy', 'organization': {'class': 'OTHER', 'fullName': 'Pennington Biomedical Research Center'}, 'orgStudyIdInfo': {'id': 'PBRC 2015-019'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Healthy Men', 'interventionNames': ['Behavioral: Fasting']}], 'interventions': [{'name': 'Fasting', 'type': 'BEHAVIORAL', 'description': '72 hour fasting', 'armGroupLabels': ['Healthy Men']}]}, 'contactsLocationsModule': {'locations': [{'zip': '70808-4124', 'city': 'Baton Rouge', 'state': 'Louisiana', 'country': 'United States', 'facility': 'Pennington Biomedical Research Center', 'geoPoint': {'lat': 30.44332, 'lon': -91.18747}}], 'overallOfficials': [{'name': 'David McDougal, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Pennington Biomedical Rsrch Ct'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Pennington Biomedical Research Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor', 'investigatorFullName': 'David McDougal', 'investigatorAffiliation': 'Pennington Biomedical Research Center'}}}}