Ignite Creation Date:
2025-12-24 @ 11:14 PM
Ignite Modification Date:
2026-02-24 @ 11:00 AM
Study NCT ID:
NCT01999569
Status:
COMPLETED
Last Update Posted:
2022-04-22
First Post:
2013-11-26
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
The Role of Estrogen in Luteinizing Hormone Surge and Ovulation
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010048', 'term': 'Ovarian Cysts'}], 'ancestors': [{'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'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077289', 'term': 'Letrozole'}], 'ancestors': [{'id': 'D009570', 'term': 'Nitriles'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'bhurst@carolinas.org', 'phone': '704-355-3149', 'title': 'Bradley Hurst, M.D., Director of Assisted Reproduction', 'organization': 'Carolinas Healthcare System'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'two ovulation cycles (2 months)', 'eventGroups': [{'id': 'EG000', 'title': 'Control', 'description': 'Control cycle. No intervention.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Letrozole', 'description': '5mg daily\n\nLetrozole: Letrozole administered daily through the time of ovulation.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants With Progesterone Level Greater Than 1.5 ng/mL', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Control', 'description': 'Control cycle'}, {'id': 'OG001', 'title': 'Letrozole Treatment Cycle'}], 'classes': [{'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Cycle days 12-22', 'description': 'Serum progesterone ng/mL drawn during cycle days twelve through 22', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With a Positive LH Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Control', 'description': 'Control cycle'}, {'id': 'OG001', 'title': 'Letrozole Treatment Cycle'}], 'classes': [{'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Cycle days 10-18', 'description': 'Urine ovulation tests assessed', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Follicular Development', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Control', 'description': 'Control cycle.'}, {'id': 'OG001', 'title': 'Letrozole Treatment Cycle'}], 'classes': [{'categories': [{'measurements': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Cycle day 12', 'description': 'Ovulation; elevated progesterone', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Control Then Letrozole', 'description': 'Control cycle. Then letrozole cycle'}], 'periods': [{'title': 'Control Cycle', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'First cycle no meds', 'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}, {'title': 'Letrozole Treatment Cycle', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Ovulatory volunteers'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Control', 'description': 'Control cycle. Then letrozole cycle'}], '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': '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': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', '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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2007-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-10', 'completionDateStruct': {'date': '2008-05', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-04-20', 'studyFirstSubmitDate': '2013-11-26', 'resultsFirstSubmitDate': '2015-02-09', 'studyFirstSubmitQcDate': '2013-11-26', 'lastUpdatePostDateStruct': {'date': '2022-04-22', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-10-07', 'studyFirstPostDateStruct': {'date': '2013-12-03', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-11-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2008-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants With Progesterone Level Greater Than 1.5 ng/mL', 'timeFrame': 'Cycle days 12-22', 'description': 'Serum progesterone ng/mL drawn during cycle days twelve through 22'}], 'secondaryOutcomes': [{'measure': 'Number of Participants With a Positive LH Test', 'timeFrame': 'Cycle days 10-18', 'description': 'Urine ovulation tests assessed'}, {'measure': 'Number of Participants With Follicular Development', 'timeFrame': 'Cycle day 12', 'description': 'Ovulation; elevated progesterone'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Ovulation Disorder', 'Ovarian Cysts']}, 'referencesModule': {'references': [{'pmid': '22438212', 'type': 'BACKGROUND', 'citation': 'Christensen A, Bentley GE, Cabrera R, Ortega HH, Perfito N, Wu TJ, Micevych P. Hormonal regulation of female reproduction. Horm Metab Res. 2012 Jul;44(8):587-91. doi: 10.1055/s-0032-1306301. Epub 2012 Mar 21.'}, {'pmid': '2657783', 'type': 'BACKGROUND', 'citation': 'Morioka N, Zhu C, Brannstrom M, Woessner JF, LeMaire WJ. Mechanism of mammalian ovulation. Prog Clin Biol Res. 1989;294:65-85.'}, {'pmid': '3055821', 'type': 'BACKGROUND', 'citation': 'Goh HH, Ratnam SS. The LH surge in humans: its mechanism and sex difference. Gynecol Endocrinol. 1988 Jun;2(2):165-82. doi: 10.3109/09513598809023624.'}, {'pmid': '16782289', 'type': 'BACKGROUND', 'citation': 'Laven JS, Fauser BC. What role of estrogens in ovarian stimulation. Maturitas. 2006 Jul 20;54(4):356-62. doi: 10.1016/j.maturitas.2006.04.022. Epub 2006 Jun 19.'}, {'pmid': '16384846', 'type': 'BACKGROUND', 'citation': 'Casper RF, Mitwally MF. Review: aromatase inhibitors for ovulation induction. J Clin Endocrinol Metab. 2006 Mar;91(3):760-71. doi: 10.1210/jc.2005-1923. Epub 2005 Dec 29.'}, {'pmid': '15350255', 'type': 'BACKGROUND', 'citation': 'Mitwally MF, Casper RF. Aromatase inhibition reduces the dose of gonadotropin required for controlled ovarian hyperstimulation. J Soc Gynecol Investig. 2004 Sep;11(6):406-15. doi: 10.1016/j.jsgi.2004.03.006.'}, {'pmid': '21197188', 'type': 'BACKGROUND', 'citation': 'Burstein HJ, Griggs JJ, Prestrud AA, Temin S. American society of clinical oncology clinical practice guideline update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Oncol Pract. 2010 Sep;6(5):243-6. doi: 10.1200/JOP.000082. Epub 2010 Aug 6.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of the study is to establish that sustained estrogen levels are the driving force for the LH surge, and are thereby necessary for ovulation to occur. We predict that by reducing levels of circulating estrogen, letrozole, an aromatase inhibitor, will inhibit ovulation from occurring.', 'detailedDescription': "Sine the common understanding of ovulation in a natural cycle suggests that a sustained, elevated estradiol level is required to trigger the LH surge, administration of letrozole throughout the cycle should lower estradiol levels and prevent the LH surge from occurring. In this study, we sought to determine if the LH surge, ovulation and luteinization occurs in spite of low estradiol levels by daily administration of letrozole in a group of normal ovulatory volunteers in a prospective study.\n\nAfter IRB approval and informed consent were obtained, ten willing volunteers that met inclusion criteria (no hormonal contraception within 3 months, regular menstrual cycles 26 - 30 days, normal thyroid function and normal prolactin, and no pregnancy currently or within 3 months) were monitored for one month without treatment for evaluation of normal ovulation.\n\nNatural control cycle The subjects used home urine LH tests (Clearblue® Easy, SPD Swiss Precision Diagnostics, Switzerland) on days 10-18 to monitor for the LH surge in both the initial natural cycle and the letrozole cycle. Blood was drawn every other day starting on day 12 of the cycle through day 22 to measure estradiol and progesterone levels, and follicular development was monitored using transvaginal ultrasound on cycle day 12-14.\n\nLetrozole cycle In the next cycle, all ten subjects were administered oral letrozole 5 mg daily (Femara®, Novartis Pharmaceuticals Corporation, East Hanover, NJ ) starting on cycle day 1-3 and continuing through the completion of the study (cycle day 22). Once again, serum estradiol and progesterone levels were measured every other day on days 12-22. The development of the ovarian follicles was monitored by transvaginal ultrasound once in each cycle between days 12-14, and LH surge was monitored with home urine ovulation tests on days 10-18. Table 1 illustrates protocols for both the natural control cycle and the letrozole study cycle.\n\nThe primary outcome, assessment of ovulation in letrozole cycles, was determined by the presence or absence of progesterone elevation (\\>1.5 ng/mL) and the presence or absence of a positive urinary LH test. The bioequivalence evaluation of two cycles (before and after letrozole administration) was based on pharmacokinetic parameters such as area under the serum concentration-time curve (AUC), the peak serum concentration (Cmax) and the time of peak serum concentration (Tmax). Cmax and Tmax were determined by visual inspection from each volunteer's serum concentration-time curve for estradiol and progesterone. AUC was calculated by the linear trapezoidal method from day 12 through day 22 in both the initial natural cycle and the letrozole cycle.\n\nPaired t-tests, or Wilcoxon Signed Rank tests if non-normally distributed, were used to evaluate the statistical significance of the mean values of the pharmacokinetic parameters. The McNemar test was used to assess the difference in LH surge and follicular development before and after letrozole administration. A standard of statistical significance (alpha) of 0.05 was used in all cases. The SAS System (SAS Institute, Cary, NC) was used for all analyses."}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patient having regular menstrual cycles between 26-30 days\n* Ages 18-40\n* Patient must not be sexually active during the study period, or if so must be using a reliable form of non-hormonal birth control including tubal ligation or vasectomy, non-hormonal intrauterine contraceptive device (IUD), or condoms with spermicide.\n* Willing to participate in study and available for all monitoring visits.\n* IRB consent\n\nExclusion Criteria:\n\n* Patient must NOT have used hormonal contraception three months or less prior to study.\n* Irregular menstrual cycles (\\<26 days or \\>30 days within the last 6 months.\n* Untreated thyroid dysfunction or hyperprolactinemia\n* Pregnancy (current or within 3 months) or breastfeeding\n* Allergy or contraindication to letrozole'}, 'identificationModule': {'nctId': 'NCT01999569', 'briefTitle': 'The Role of Estrogen in Luteinizing Hormone Surge and Ovulation', 'organization': {'class': 'OTHER', 'fullName': 'Wake Forest University Health Sciences'}, 'officialTitle': 'The Role of Estrogen in Luteinizing Hormone Surge and Ovulation', 'orgStudyIdInfo': {'id': 'LH-2013'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'Control', 'description': 'Control cycle. No intervention.'}, {'type': 'EXPERIMENTAL', 'label': 'Letrozole', 'description': '5mg daily', 'interventionNames': ['Drug: Letrozole']}], 'interventions': [{'name': 'Letrozole', 'type': 'DRUG', 'otherNames': ['Femara'], 'description': 'Letrozole administered daily through the time of ovulation.', 'armGroupLabels': ['Letrozole']}]}, 'contactsLocationsModule': {'locations': [{'zip': '28204', 'city': 'Charlotte', 'state': 'North Carolina', 'country': 'United States', 'facility': "Women's Institute at Carolinas Medical Center", 'geoPoint': {'lat': 35.22709, 'lon': -80.84313}}], 'overallOfficials': [{'name': 'Brad S Hurst, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Wake Forest University Health Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Wake Forest University Health Sciences', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}