Ignite Creation Date:
2025-12-24 @ 2:14 PM
Ignite Modification Date:
2025-12-25 @ 12:52 PM
Study NCT ID:
NCT01427595
Status:
COMPLETED
Last Update Posted:
2021-01-08
First Post:
2011-08-30
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011085', 'term': 'Polycystic Ovary Syndrome'}, {'id': 'D017588', 'term': 'Hyperandrogenism'}], 'ancestors': [{'id': 'D010048', 'term': 'Ovarian Cysts'}, {'id': 'D003560', 'term': 'Cysts'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010049', 'term': 'Ovarian Diseases'}, {'id': 'D000291', 'term': 'Adnexal Diseases'}, {'id': 'D005831', 'term': 'Genital Diseases, Female'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D006058', 'term': 'Gonadal Disorders'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D058489', 'term': '46, XX Disorders of Sex Development'}, {'id': 'D012734', 'term': 'Disorders of Sex Development'}, {'id': 'D014564', 'term': 'Urogenital Abnormalities'}, {'id': 'D047808', 'term': 'Adrenogenital Syndrome'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D000013', 'term': 'Congenital Abnormalities'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008687', 'term': 'Metformin'}, {'id': 'D011374', 'term': 'Progesterone'}, {'id': 'D004958', 'term': 'Estradiol'}, {'id': 'D004967', 'term': 'Estrogens'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011282', 'term': 'Pregnenediones'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D003339', 'term': 'Corpus Luteum Hormones'}, {'id': 'D042341', 'term': 'Gonadal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D045167', 'term': 'Progesterone Congeners'}, {'id': 'D012739', 'term': 'Gonadal Steroid Hormones'}, {'id': 'D004963', 'term': 'Estrenes'}, {'id': 'D004962', 'term': 'Estranes'}, {'id': 'D045166', 'term': 'Estradiol Congeners'}, {'id': 'D045505', 'term': 'Physiological Effects of Drugs'}, {'id': 'D020228', 'term': 'Pharmacologic Actions'}, {'id': 'D020164', 'term': 'Chemical Actions and Uses'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'pcos@virginia.edu', 'phone': '4342436911', 'title': 'Dr. Christine Burt Solorzano', 'organization': 'University of Virginia Center for Research in Reproduction'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'From start of study procedures until 30 days post study drug.', 'eventGroups': [{'id': 'EG000', 'title': 'Metformin, Progesterone , Estrace', 'description': '12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)\n\nMetformin: 500-2000 mg PO BID (X12 weeks)\n\nProgesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)\n\nestrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2', 'otherNumAtRisk': 25, 'deathsNumAtRisk': 25, 'otherNumAffected': 12, 'seriousNumAtRisk': 25, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Vision switched from near to farsighted', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'SVT', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'UTI', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'fainting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Acute Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'heartburn', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'vomitting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 25, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in Progesterone Sensitivity Index Before and After Metformin Treatment.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin, Progesterone , Estrace', 'description': '12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)\n\nMetformin: 500-2000 mg PO BID (X12 weeks)\n\nProgesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)\n\nestrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2'}], 'classes': [{'title': 'Before Metformin', 'categories': [{'measurements': [{'value': '-4.12', 'spread': '2.39', 'groupId': 'OG000'}]}]}, {'title': 'After Metformin', 'categories': [{'measurements': [{'value': '-4.29', 'spread': '7.66', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '12 weeks following start of metformin treatment', 'description': 'The progesterone (P4) sensitivity index is defined as the percent change in 11-hour LH pulse frequency before and after P4 and estradiol administration for 7 days, divided by the day 7 mean serum P4 concentration. We compared the P4 sensitivity index after metformin administration to the baseline P4 sensitivity index, using Wilcoxon signed-rank test.', 'unitOfMeasure': '% change in LH pulses/day 7 P4 level', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': '12 subjects completed study but 2 subjects were excluded from analysis due to incomplete adherence to metformin, missing \\> 10% of doses.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Metformin, Progesterone , Estrace', 'description': '12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)\n\nMetformin: 500-2000 mg PO BID (X12 weeks)\n\nProgesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)\n\nestrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '25'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}]}], 'preAssignmentDetails': '25 subjects enrolled in this study. 7 subjects completed screening procedures only (these 7 subjects were withdrawn from study prior to being assigned to an arm of intervention).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Metformin, Progesterone , Estrace', 'description': '12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)\n\nMetformin: 500-2000 mg PO BID (X12 weeks)\n\nProgesterone: oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)\n\nestrace: oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '15.3', 'spread': '1.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '0', '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': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '2', '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': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': '25 subjects enrolled and 12 completed the study. Only 10 subjects were included in the formal analysis.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-12-14', 'size': 1004541, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-11-18T13:39', 'hasProtocol': True}, {'date': '2015-12-14', 'size': 379009, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2020-11-18T13:40', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 25}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-02-18', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-12', 'completionDateStruct': {'date': '2015-01-17', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-14', 'studyFirstSubmitDate': '2011-08-30', 'resultsFirstSubmitDate': '2020-12-14', 'studyFirstSubmitQcDate': '2011-08-31', 'lastUpdatePostDateStruct': {'date': '2021-01-08', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-12-14', 'studyFirstPostDateStruct': {'date': '2011-09-01', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-01-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2015-01-17', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Progesterone Sensitivity Index Before and After Metformin Treatment.', 'timeFrame': '12 weeks following start of metformin treatment', 'description': 'The progesterone (P4) sensitivity index is defined as the percent change in 11-hour LH pulse frequency before and after P4 and estradiol administration for 7 days, divided by the day 7 mean serum P4 concentration. We compared the P4 sensitivity index after metformin administration to the baseline P4 sensitivity index, using Wilcoxon signed-rank test.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['hyperandrogenemia'], 'conditions': ['Polycystic Ovary Syndrome', 'Hyperandrogenism']}, 'referencesModule': {'references': [{'pmid': '29095983', 'type': 'DERIVED', 'citation': 'Lundgren JA, Kim SH, Burt Solorzano CM, McCartney CR, Marshall JC. Progesterone Suppression of Luteinizing Hormone Pulse Frequency in Adolescent Girls With Hyperandrogenism: Effects of Metformin. J Clin Endocrinol Metab. 2018 Jan 1;103(1):263-270. doi: 10.1210/jc.2017-02068.'}]}, 'descriptionModule': {'briefSummary': 'Many, but not all, girls with high levels of the male hormone testosterone go on to develop polycystic ovary syndrome (PCOS) as adults. Women with PCOS often have irregular menstrual periods, excess facial and body hair, and weight gain. PCOS is also a leading cause of difficulty becoming pregnant. The investigators do not understand why some girls with high hormones develop PCOS and others do not. In a previous study by our group, some girls with high levels of male hormones had abnormalities in the secretion of another hormone, called luteinizing hormone (LH), that are often seen in women with PCOS. However, another group had normal LH secretion. The girls with the abnormal LH secretion had higher levels of another hormone, called insulin, than the girls with normal LH secretion. The investigators will test whether metformin, an insulin-sensitizing agent, changes the effects of high male hormone levels in adolescent girls, specifically by looking at their LH secretion response following metformin treatment.', 'detailedDescription': 'A better understanding of the factors that make adolescent girls more or less susceptible to the adverse neuroendocrine effects of elevated androgens will hopefully lead to improved prevention and treatment strategies for PCOS. In this study, we propose to explore the role of hyperinsulinemia on neuroendocrine function in hyperandrogenic adolescent girls by assessing the effect of the insulin sensitizer Metformin on hypothalamic progesterone sensitivity. Other differences between the progesterone sensitive and progesterone insensitive subgroups, including racial and ethnic differences between the two populations and a trend towards older gynecologic age in the progesterone insensitive population, are being pursued through other ongoing studies (IRB-HSR# 8588 and 12160).'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'minimumAge': '10 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Girls ages 10 to 17\n* Hyperandrogenemic (free testosterone greater than 2.5 standard deviations above the mean for normal control subjects of the same Tanner Stage)\n* Creatinine clearance \\> 90 ml/min as calculated by the Cockcroft-Gault equation\n* Hemoglobin \\> 12 mg/dL or Hematocrit \\> 36%\n* Normal screening labs (with exception of the expected hormonal abnormalities inherent in hyperandrogenemia)\n* Sexually active subjects must agree to abstain or use double barrier contraception during the study\n* Subjects must agree not to take any other medications during the course of the study without approval by the study investigators.\n\nExclusion Criteria:\n\n* Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia)\n* Creatinine clearance less than 90 ml/min as calculated by Cockcroft-Gault equation\n* Hemoglobin \\<12 mg/dL or hematocrit \\< 36%\n* Abnormal liver function tests, including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin, Albumin, and Alkaline Phosphatase\n* Weight \\< 34 kg\n* History of renal dysfunction, liver dysfunction, congestive heart failure, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer\n* Pregnant or breast feeding\n* On medications known to affect the reproductive axis within 3 months of the study (including oral contraceptive pills, metformin, and spironolactone)\n* Are currently participating in another study or have been in one in the last 30 days.\n* Subjects using restricted medication (see restrictions below) are excluded unless the subject's primary care provider approves stopping the medication."}, 'identificationModule': {'nctId': 'NCT01427595', 'briefTitle': 'Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone', 'organization': {'class': 'OTHER', 'fullName': 'University of Virginia'}, 'officialTitle': 'Effect of Metformin on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenemic Adolescent Girls (JCM025)', 'orgStudyIdInfo': {'id': '13789'}, 'secondaryIdInfos': [{'id': 'U54HD028934-18', 'link': 'https://reporter.nih.gov/quickSearch/U54HD028934-18', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Metformin, progesterone , estrace', 'description': '12 weeks Metformin oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (2X) oral estrace, 0.5-1 mg once a day for seven days (2X)', 'interventionNames': ['Drug: Metformin', 'Drug: Progesterone', 'Drug: estrace']}], 'interventions': [{'name': 'Metformin', 'type': 'DRUG', 'description': '500-2000 mg PO BID (X12 weeks)', 'armGroupLabels': ['Metformin, progesterone , estrace']}, {'name': 'Progesterone', 'type': 'DRUG', 'description': 'oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days (X2)', 'armGroupLabels': ['Metformin, progesterone , estrace']}, {'name': 'estrace', 'type': 'DRUG', 'otherNames': ['Estrogen'], 'description': 'oral estrogen (estrace, 0.5-1 mg once a day for seven days)- X2', 'armGroupLabels': ['Metformin, progesterone , estrace']}]}, 'contactsLocationsModule': {'locations': [{'zip': '22908', 'city': 'Charlottesville', 'state': 'Virginia', 'country': 'United States', 'facility': 'Center for Research in Reproduction, University of Virginia', 'geoPoint': {'lat': 38.02931, 'lon': -78.47668}}], 'overallOfficials': [{'name': 'John C. Marshall, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Virginia'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Virginia', 'class': 'OTHER'}, 'collaborators': [{'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Center for Research in Reproduction', 'investigatorFullName': 'Christine Burt Solorzano', 'investigatorAffiliation': 'University of Virginia'}}}}