[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100596158":3},{"organization":4,"armGroups":7,"interventions":20,"overallOfficials":31,"centralContacts":43,"locations":53,"responsibleParty":71,"collaborators":26,"id":73,"slug":74,"hasResults":75,"nctId":76,"briefTitle":77,"officialTitle":78,"acronym":79,"eligibilityCriteria":80,"healthyVolunteers":75,"sex":81,"minAge":82,"maxAge":83,"enrollmentInfo":84,"targetDuration":26,"studyType":87,"phases":88,"briefSummary":90,"conditions":91,"keywords":93,"overallStatus":100,"whyStopped":26,"lastUpdateSubmitDate":101,"lastUpdatePostDateStruct":102,"startDateStruct":105,"completionDateStruct":107,"leadSponsor":109,"locationsCount":110},{"fullName":5,"class":6},"Universiti Kebangsaan Malaysia Medical Centre","OTHER",[8,14],{"label":9,"type":10,"description":11,"interventionNames":12},"Oral Estradiol Valerate (Progynova)","ACTIVE_COMPARATOR","Progynova is an oral hormone replacement therapy containing the active ingredient estradiol valerate, a synthetic ester of 17β-estradiol that, upon ingestion, is rapidly converted to bioidentical estradiol. Each film-coated tablet delivers either 1 mg or 2 mg of estradiol valerate, with inactive excipients including lactose monohydrate, maize starch, povidone, magnesium stearate, and hypromellose. Progynova tablets are supplied in blister packs of 28 tablets, with recommended storage at room temperature (15-30 °C), protected from moisture and direct sunlight. In this trial, Progynova will be administered starting at 1 mg twice weekly and titrated up to 4 mg daily over an 18-month period, in accordance with local clinical guidelines for pubertal induction in Turner Syndrome.",[13],"Drug: Oral estradiol valerate",{"label":15,"type":16,"description":17,"interventionNames":18},"Transdermal 17β estradiol (Oestrogel®)","EXPERIMENTAL","Oestrogel® is a transdermal hormone replacement therapy containing 17β-estradiol in a hydroalcoholic gel formulation designed for topical application. Each pump actuation delivers 0.75 mg of estradiol in a 1.25 g dose of gel, which is formulated with excipients including ethanol, propylene glycol, carbomer, sodium hydroxide, and purified water to ensure consistent hormone release and skin penetration. The gel is supplied in multi-dose pump bottles (150 g), each providing up to 120 actuations. In this trial, Oestrogel® will be administered starting at one pump actuation (0.75 mg) twice weekly, with dose escalation every 3 months according to predefined protocol milestones, up to a maximum of four actuations daily (3 mg estradiol) over an 18-month induction period. Participants will be instructed on correct application technique-applying gel to clean, dry skin and allowing at least 5 minutes for drying before dressing-to ensure optimal absorption and minimize residue transfer",[19],"Drug: Transdermal 17β estradiol",[21,27],{"type":22,"name":23,"description":24,"armGroupLabels":25,"otherNames":26},"DRUG","Oral estradiol valerate","Progynova is an oral hormone replacement therapy containing the active ingredient estradiol valerate, a synthetic ester of 17β-estradiol that, upon ingestion, is rapidly converted to bioidentical estradiol. Each film-coated tablet delivers either 1 mg or 2 mg of estradiol valerate, with inactive excipients including lactose monohydrate, maize starch, povidone, magnesium stearate, and hypromellose. In terms of pharmacokinetics, oral estradiol valerate undergoes first-pass metabolism in the liver, yielding a peak serum estradiol concentration within 4-8 hours of dosing and a biological half-life of approximately 20 hours. Progynova tablets are supplied in blister packs of 28 tablets, with recommended storage at room temperature (15-30 °C), protected from moisture and direct sunlight.",[9],null,{"type":22,"name":28,"description":29,"armGroupLabels":30,"otherNames":26},"Transdermal 17β estradiol","Oestrogel® is a transdermal hormone replacement therapy containing 17β-estradiol in a hydroalcoholic gel formulation designed for topical application. Each pump actuation delivers 0.75 mg of estradiol in a 1.25 g dose of gel, which is formulated with excipients including ethanol, propylene glycol, carbomer, sodium hydroxide, and purified water to ensure consistent hormone release and skin penetration. Upon application to intact skin-typically the forearm or thigh-the gel allows for direct systemic absorption of estradiol, bypassing first-pass hepatic metabolism. Peak serum estradiol levels are generally reached within 6-12 hours post-application, with a half-life of approximately 10-20 hours, resulting in more physiological, steady- steady-state estradiol exposure compared to oral formulations. The gel is supplied in multi-dose pump bottles (150 g), each providing up to 120 actuations.",[15],[32,36,40],{"name":33,"affiliation":34,"role":35},"MUHAMMAD IRFAN ABDUL JALAL, MBChB BAO, PhD","Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI)","STUDY_CHAIR",{"name":37,"affiliation":38,"role":39},"ANI AMELIA ZAINUDDIN, MBBS, PhD","FACULTY OF MEDICINE, UNIVERSITI KEBANGSAAN MALAYSIA","PRINCIPAL_INVESTIGATOR",{"name":41,"affiliation":42,"role":39},"NUR AZURAH ABDUL GHANI, MBBS, MMed (Obs and Gynae)","National University of Malaysia",[44,49],{"name":37,"role":45,"phone":46,"phoneExt":47,"email":48},"CONTACT","+60391455950","+60193882078","aniamelia@ukm.edu.my",{"name":33,"role":45,"phone":50,"phoneExt":51,"email":52},"+6039145 6321","+60172107299","irfan.abduljalal@ukm.edu.my",[54],{"facility":55,"status":26,"city":56,"state":57,"zip":58,"country":59,"countryCode":60,"cosmosGeoPoint":26,"geoPoint":26,"contacts":61},"Hospital Canselor Tuanku Muhriz (HCTM)","Cheras","Kuala Lumpur","56000","Malaysia","MY",[62,63,65,66,67,69],{"name":37,"role":45,"phone":46,"phoneExt":47,"email":48},{"name":33,"role":45,"phone":64,"phoneExt":51,"email":52},"+60391456321",{"name":37,"role":39,"phone":26,"phoneExt":26,"email":26},{"name":33,"role":39,"phone":26,"phoneExt":26,"email":26},{"name":41,"role":68,"phone":26,"phoneExt":26,"email":26},"SUB_INVESTIGATOR",{"name":70,"role":68,"phone":26,"phoneExt":26,"email":26},"Esther Sweet Yi Loh, MBBS, Dr(Obstetrics & Gynae)",{"type":72,"investigatorFullName":26,"investigatorTitle":26,"investigatorAffiliation":26,"oldNameTitle":26,"oldOrganization":26},"SPONSOR","100596158","phase-2-a-study-comparing-different-treatment-approaches-for-the-initiation-of-puberty-in-girls-with-turner-syndrome-using-a-trifecta-dared-approach-for-rare-diseases-100596158",false,"NCT07041814","A Study Comparing Different Treatment Approaches for the Initiation of Puberty in Girls With Turner Syndrome Using a TRIFECTA-DARED Approach for Rare Diseases","Bayesian Pragmatic Trial for Pubertal Induction in Turner Syndrome: TRansformation Initiative For Efficient Clinical TriAl Design Advancement in RarE Diseases (TRIFECTA-DARED Framework)","TRIFECTA-DARED","Inclusion Criteria:\n\n1. Females aged 11-30 years old with karyotype-verified (45, X or other similar karyotypes) and clinically confirmed Turner's syndrome prior at the time of pubertal induction\n2. Confirmed estrogen deficiency with primary ovarian failure (high level of follicular stimulating hormone (FSH \\> 25 IU\u002FL))\n3. Patients who have not undergone pubertal development ( no breast development and underdeveloped uterus size).\n4. Hormone Replacement Therapy (HRT)-naive TS patients\n5. Breast Tanner Stage of 2 or less.\n6. Patients on Growth Hormone (GH) will be allowed entry into the study.\n7. Consented to trial participation (from individual TS patients (if aged 18 and above) or the parents or guardians (for under-18 TS patients) with individual's assent\n\nExclusion Criteria:\n\n1. Patients with signs of spontaneous puberty\n2. Contraindications to trial products (e.g hypersensitivity to any components of the HRT) based on the most recent version of the British National Formulary (BNF 85)\n3. Previous history of exposure to estrogen treatment.\n4. Concomitant use of other drugs that affect the bone mineral density (BMD) of the participants (e.g. Bisphosphonates or prolonged use of systemic corticosteroids). Vitamin D supplementation and short corticosteroid usage are allowed.\n5. Acute or chronic hepatic disease\n6. Patients with untreated hypothyroidism\n7. Inflammatory bowel disease (Ulcerative Colitis, Crohn's disease) and coeliac disease\n8. Cigarette-smoking patients\n9. Severely obese patients based on the following criteria:\n\n   1. For TS patients aged 11-17 years old: Based on the WHO chart with BMI \\> 95th percentile\n   2. For TS patients aged 18 years until 30 years: BMI of 37.5 or above based on the Malaysian Clinical Practice Guideline for the Management of Obesity\n10. Unknown abnormal genital bleeding\n11. Porphyria\n12. Recent involvement with clinical research studies (previous 6 months) investigating new HRT formulations","FEMALE","11 Years","30 Years",{"count":85,"type":86},24,"ESTIMATED","INTERVENTIONAL",[89],"PHASE2","Turner syndrome is a condition in which a girl's body does not make enough estrogen on its own, so doctors give estrogen to help start breast and uterine (womb) development. Hence, the goal of this clinical trial is to learn whether two different ways of giving estrogen help girls and young women with Turner syndrome go through puberty normally, and to compare how well each method works and how safe they are.\n\nThe main questions the trial aims to answer are:\n\n1. Does taking an oral estrogen tablet (Progynova) or applying an estrogen gel (Oestrogel) lead to better breast development?\n2. Does one method lead to a larger uterine size as seen on ultrasound?\n3. Do participants start menstrual-like (withdrawal) bleeding, and does one method cause it sooner?\n4. What side effects (for example, headaches, nausea, changes in blood tests) happen with each method?\n\nWho can take part?\n\n* Girls and young women aged 11-30 years with a confirmed diagnosis of Turner syndrome and no previous estrogen treatment.\n* They have not yet begun puberty (no breast growth, and a small uterus on ultrasound).\n* They agree to adhere to the study schedule and keep a diary of any bleeding or side effects\n\nWhat will happen to the participants during the clinical trial?\n\n* Get assigned at random to one of two groups (1:1 ratio):\n\n  1. Gel group: Apply Oestrogel (17β-estradiol) to the skin, starting twice a week, then daily with increasing doses over 19 months.\n  2. Tablet group: Swallow Progynova (estradiol valerate) tablets, starting twice a week, then daily with increasing doses over 19 months.\n* Visit the clinic at the start of study (baseline), month 1, 7, 13, and 19 for:\n\n  1. A physical exam (including breast staging).\n  2. An ultrasound to measure uterine length and thickness.\n  3. A blood test for safety checks (triglycerides and other markers).\n  4. Keep a diary noting any spotting or bleeding (called withdrawal bleeding) and any side effects.\n\nWhy does this matter?\n\nGirls and young women with Turner syndrome often need estrogen to begin puberty safely. This trial will show which method-gel or tablets-best mimics natural puberty (breast and uterine growth), how quickly menstrual-like bleeding begins, and which has fewer unwanted effects. The findings will help doctors choose the most effective and safe treatment for people with Turner syndrome.",[92],"Turner Syndrome",[92,94,95,96,97,98,99],"Hormone Replacement Therapy","Progynova","Oestrogel","Transdermal 17β Estradiol","Estradiol Valerate","Pubertal Induction","NOT_YET_RECRUITING","2026-01-28",{"date":103,"type":104},"2026-02-02","ACTUAL",{"date":106,"type":86},"2026-02-15",{"date":108,"type":86},"2029-10-31",{"name":5,"class":6},1]