Ignite Creation Date:
2025-12-24 @ 4:19 PM
Ignite Modification Date:
2025-12-24 @ 4:19 PM
Study NCT ID:
NCT04192266
Status:
COMPLETED
Last Update Posted:
2025-04-10
First Post:
2019-10-17
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Estrogen and Fear in PTSD
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'submissionInfos': [{'resetDate': '2025-12-16', 'mcpReleaseN': 12, 'releaseDate': '2025-12-02'}], 'estimatedResultsFirstSubmitDate': '2025-12-02'}}, 'conditionBrowseModule': {'meshes': [{'id': 'D013313', 'term': 'Stress Disorders, Post-Traumatic'}], 'ancestors': [{'id': 'D040921', 'term': 'Stress Disorders, Traumatic'}, {'id': 'D000068099', 'term': 'Trauma and Stressor Related Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D004958', 'term': 'Estradiol'}, {'id': 'D013812', 'term': 'Therapeutics'}], 'ancestors': [{'id': 'D004963', 'term': 'Estrenes'}, {'id': 'D004962', 'term': 'Estranes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D045166', 'term': 'Estradiol Congeners'}, {'id': 'D012739', 'term': 'Gonadal Steroid Hormones'}, {'id': 'D042341', 'term': 'Gonadal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER'], 'maskingDescription': 'double blinded'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 64}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-06-24', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-04', 'dispFirstSubmitDate': '2025-03-18', 'completionDateStruct': {'date': '2024-12-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-04-09', 'studyFirstSubmitDate': '2019-10-17', 'studyFirstSubmitQcDate': '2019-12-09', 'dispFirstPostDateStruct': {'date': '2025-01-31', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2025-04-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-12-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-05-29', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Extinction-induced functional MRI (fMRI) responses', 'timeFrame': 'Experimental Day 2', 'description': 'The outcome measure is brain activation within fear extinction network.'}, {'measure': 'Skin Conductance Response (SCR) during recall', 'timeFrame': 'Experimental Day 1, Experimental Day 2', 'description': 'Skin Conductance Response (SCR) assesses the stress/seat level, or level of anxiety in a particular moment, or in response to a specific cue. SCR will be reported in microsiemens.'}], 'secondaryOutcomes': [{'measure': 'Change from Baseline on PTSD symptom severity', 'timeFrame': 'Visit 13 -15 (1, 3, and 6 months follow up)', 'description': 'The outcome measure is change in PTSD severity as indexed by CAPS scores.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['PTSD']}, 'descriptionModule': {'briefSummary': 'The purpose of this research study is to determine if taking a pill of estradiol (E2) together with prolonged exposure (PE) therapy can improve this treatment outcome in women diagnosed with Post-Traumatic Stress Disorder (PTSD). 80 subjects will take part in this research study across UTHealth Houston and UPenn (40 subjects at each site). Participants will be randomized into one of two groups, PE + E2 or PE + placebo. The study will include preliminary screening and baseline visits, experimental visits, and therapy visits over the course of six weeks. Several follow-up visits will take place.', 'detailedDescription': 'Prolonged-exposure (PE) therapy is the treatment of choice for posttraumatic stress disorder (PTSD). Despite its efficacy, a significant number of individuals will not benefit from it or might drop out before the completion of all sessions. This underlies the importance of findings ways to enhance the efficacy of PE in order to improve the life quality of individuals suffering from PTSD. It is now widely accepted that extinction learning paradigms used in fundamental studies are useful laboratory analogs to PE. Studies in healthy controls have suggested that elevated estrogen levels benefit extinction learning by promoting its consolidation and thus enhancing its recall when tested later for it. This is also being reflected by changes in the activation of brain regions forming the fear extinction network, including the amygdala, dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortex (vmPFC). It is still unknown whether estradiol (E2) administration can modulate the activation of the fear extinction network in oral contraceptive (OC) users and which E2 dose could yield the best results. During the R61 phase of the study, we found that both doses of E2 were effective in engaging the functional activation of the fear extinction network. Therefore, we will use the lower dose (2mg) for the R33 phase. We will combine E2 administration with PE sessions to see if administration of PE can significantly improve clinical outcomes (reduced PTSD symptoms) and engage the fear extinction network in the brain.\n\nHypothesis: A general improvement is expected after 3 weeks of treatment in both groups given the anticipated benefits of PE alone. But the benefit of the Estradiol-treated groups is hypothesized be larger; with this group exhibiting significantly higher activation in brain regions associated with fear extinction. This will be noted at the follow-up scan compared to the baseline scan.\n\nPTSD symptom severity expected be significantly lower in the Estradiol and PE group relative to the Placebo+PE group following acute treatment after three weeks of treatment.\n\nThe degree of PTSD symptom reduction post- compared to pre-PE after 3 weeks of treatment is expected be associated with BOLD changes in the fear extinction network and reduction in SCR during the extinction recall test after PE. The magnitude of BOLD and SCR changes will be significantly larger in the E2+PE group compared to the Plc+PE group.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'genderBased': True, 'genderDescription': 'Estrogens are female sex hormones that are primarily produced by the ovaries and include estrone (E1), estradiol (E2) and estriol (E3). E2 is the predominant and most potent circulating estrogen produced during the reproductive years in non-pregnant women and is commonly prescribed in pill and transdermal form to treat postmenopausal symptoms', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Female, 18-45 years of age\n2. Chronic (at least one month post-trauma) DSM-5 FULL PTSD diagnosis OR subPTSD diagnosis (subPTSD defined as: meeting criterion A, F, G, H, and clusters B, C, and at least 1 of the clusters D or E.)\n3. CAPS-5 Past Month score ≥ 20\n4. Criterion A traumatic event\n5. Stable medications for 3 or more months by the time of study entrance (with the exception of benzodiazepines)\n6. Women on oral contraceptives, specifically those using monophasic or biphasic of first, second, third or fourth generation with up to 35mcg of ethinyl estradiol; OR using etonogestrel / ethinyl estradiol 0.120mg/0.015mg per day vaginal ring birth control; OR using the norelgestromin / ethinyl estradiol 0.150mg/0.035mg per day transdermal patch birth control.\n7. Willing and able to provide informed consent\n\nExclusion Criteria:\n\n1. Diagnosis of bipolar I disorder with a past year manic episode\n2. Diagnosis of a psychotic disorder or psychotic symptoms that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment.\n3. Diagnosis of moderate or severe substance use disorder that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment.\n4. Cognitive impairment that would interfere with the ability to focus on posttraumatic stress disorder (PTSD) in clinic, as determined by clinical judgment.\n5. History of neurological disease (that involves the brain), seizure, or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion).\n6. Suicidal ideation with imminent risk that warrants a higher level of care.\n7. Concurrent trauma focused psychotherapy\n8. Pregnancy (to be ruled out by urine ß-HCG).\n9. Metallic implants or devices contraindicating magnetic resonance imaging by interfering with patient safety or fMRI data collection. Cases will be cleared by the Principal Investigator and/or Baylor College of Medicine (Imaging).\n10. History of breast cancer or hormone-responsive cancer.\n11. Use of benzodiazepines\n12. Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily.\n13. High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process, based on investigator/clinician clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)'}, 'identificationModule': {'nctId': 'NCT04192266', 'briefTitle': 'Estrogen and Fear in PTSD', 'nctIdAliases': ['NCT03371654'], 'organization': {'class': 'OTHER', 'fullName': 'The University of Texas Health Science Center, Houston'}, 'officialTitle': 'A Randomized, Double-blind Placebo-controlled Multi-center Study of Identifying Neural Mechanisms of PTSD Symptom Reduction Induced by Combined Estrogen and Prolonged Exposure Therapy', 'orgStudyIdInfo': {'id': 'HSC-MS-23-0497'}, 'secondaryIdInfos': [{'id': 'R33MH111907', 'link': 'https://reporter.nih.gov/quickSearch/R33MH111907', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Prolonged Exposure (PE) therapy with Estradiol', 'description': 'A single 2mg dose of estradiol (a form of estrogen) will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD.', 'interventionNames': ['Drug: Estradiol', 'Behavioral: Prolonged Exposure (PE) therapy']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Prolonged Exposure (PE) therapy with Placebo', 'description': 'A single 2mg placebo pill will be taken at home by the study participant 5-6 hours before each of 5 prolonged exposure (PE) therapy treatment sessions (sessions 2 to 6). PE therapy is a validated treatment for PTSD.', 'interventionNames': ['Drug: Placebo oral tablet', 'Behavioral: Prolonged Exposure (PE) therapy']}], 'interventions': [{'name': 'Estradiol', 'type': 'DRUG', 'otherNames': ['Estrace'], 'description': '2.0 mg of estradiol will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions (Session 2- 6)', 'armGroupLabels': ['Prolonged Exposure (PE) therapy with Estradiol']}, {'name': 'Placebo oral tablet', 'type': 'DRUG', 'description': '2.0 mg placebo pills will be taken by mouth by the study participant 5-6 hours before each of 5 PE treatment sessions ( Sessions 2-6)', 'armGroupLabels': ['Prolonged Exposure (PE) therapy with Placebo']}, {'name': 'Prolonged Exposure (PE) therapy', 'type': 'BEHAVIORAL', 'description': 'There will be an introductory Prolonged Exposure (PE) therapy session, followed by 5 imaginal exposure sessions, such that there will be 2 sessions per week conducted for a total of 6 sessions over 3 weeks. The PE sessions are 60 minutes long and consist of imaginal exposure. Specifically, the patient is instructed to imagine the trauma and recount it aloud for about 25-30 minutes. In the following 15 minutes, the patient processes her reactions to revisiting the traumatic event by discussing related thoughts and feelings. The session ends with in vivo exposure homework to be completed that same day as the session. In the last session, imaginal exposure is conducted one last time for the same duration as previous sessions. The therapist and patient review treatment progress and discuss applications of treatment principles to daily life.', 'armGroupLabels': ['Prolonged Exposure (PE) therapy with Estradiol', 'Prolonged Exposure (PE) therapy with Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pennsylvania Perelman School of Medicine', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '77054', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'The University of Texas Health Science Center at Houston (UTHealth Houston)', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}], 'overallOfficials': [{'name': 'Mohammed R Milad, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The University of Texas Health Science Center at Houston (UTHealth Houston)'}, {'name': 'Mohammed R Milad, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The University of Texas Health Science Center, Houston'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP'], 'timeFrame': 'Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.', 'ipdSharing': 'YES', 'description': 'Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).', 'accessCriteria': 'The investigator who proposed to use the data will have access and will provide upon reasonable request.\n\nRequests should be directed to Mohammed.R.Milad@uth.tmc.edu. To gain access, data requestors will need to sign a data access agreement.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'The University of Texas Health Science Center, Houston', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Mental Health (NIMH)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Mohammed Milad', 'investigatorAffiliation': 'The University of Texas Health Science Center, Houston'}}}}