Overview
Sponsor-declared trial summary
Turner syndrome
1. Clarify endocrine, metabolic, cardiovascular, and thromboembolic risk factors in Turner syndrome after a washout period. 2. Compare the effects of oral versus transdermal estrogen replacement therapy (ERT) in women with Turner syndrome. 3. Examine the long-term effects of ERT via the two routes on endocrine, metabol…
Key facts
- Sponsor
- Region Midtjylland, Region Midtjylland
- Participant type
- Healthy volunteers, Patients
- Age range
- 18-64 years
- Gender
- Female
- Therapeutic area
- Diseases [C] - Hormonal diseases [C19]
- Trial duration
- 29 Nov 2021 → ongoing
- Decision date (initial)
- 2024-10-08
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518001-18-00
- EudraCT number
- 2019-004934-40
- ClinicalTrials.gov
- NCT06570460
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
1. Clarify endocrine, metabolic, cardiovascular, and thromboembolic risk factors in Turner syndrome after a washout period.
2. Compare the effects of oral versus transdermal estrogen replacement therapy (ERT) in women with Turner syndrome.
3. Examine the long-term effects of ERT via the two routes on endocrine, metabolic, cardiovascular, physiological, and thromboembolic risk endpoints.
Conditions and MedDRA coding
Turner syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10045181 | Turner's syndrome | 100000004850 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Diagnosis of Turner syndrome regardless of karyotype (Turner syndrome)
- Age 18-50 years (Turner syndrome and healthy controls)
- Already receiving estrogen treatment (Turner syndrome)
- Female (healthy controls)
- Previously healthy (healthy controls)
- Not receiving any medication (healthy controls)
- Not using any form of contraceptive pills (healthy controls)
- No mental or psychiatric disorders (healthy controls)
Exclusion criteria 9
- Active systemic chronic diseases
- Known or suspected breast cancer
- Known or suspected estradiol-dependent tumors (endometrial cancer or similar)
- Untreated endometrial hyperplasia
- Current or previous venous thromboembolism
- Acute or previous liver disease where liver enzymes are still elevated by a factor 3 or more
- Known hypersensitivity to the medications used
- Pregnancy
- Menopause (healthy controls only)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 9
- Body composition: measured by bio impedance
- Blood test values: changes in the blood test values from baseline within the areas of metabolism, endocrinology, cardiovascular function, and coagulation
- Cardiovascular status: 24-hour ambulatory blood pressure monitoring and arterial stiffness (measured by SphygmoCor)
- Muscle quality: MR scan of both quadriceps measuring muscle cross-sectional area (CSA) and fat content of the muscle. Maximal isometric muscle strength of both quadriceps (functional muscle tests). Muscle quality = maximum quadriceps strength measured in nM/muscle CSA.
- Quadriceps strength test: maximal isometric muscle strength of both quadriceps measured simultaneously
- Isometric hand strength test: maximal hand strength measured in kilograms
- Fitness: maximal oxygen uptake measured by a VO2max test
- Bones: bone mineral density as measured by a DEXA scan
- Jumping heigth: maximal jumping heigth measured in centimeters
Secondary endpoints 3
- Self-reported health-related quality of life and functioning (SF-36)
- Self-reported quality of life (WHOQoL-Bref)
- Subjective assesment of the medication after 6 months of oral and six months of transdermal treatment
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Estrofem, filmovertrukne tabletter
PRD341520 · Product
- Active substance
- Estradiol
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 2100 mg milligram(s)
- Max treatment duration
- 7 Month(s)
- Authorisation status
- Authorised
- ATC code
- G03CA03 — ESTRADIOL
- Marketing authorisation
- 06697
- MA holder
- NOVO NORDISK A/S
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD527570 · Product
- Active substance
- Estradiol
- Pharmaceutical form
- GEL
- Route of administration
- TRANSDERMAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 2100 mg milligram(s)
- Max treatment duration
- 7 Month(s)
- Authorisation status
- Authorised
- ATC code
- G03CA03 — ESTRADIOL
- Marketing authorisation
- 13296
- MA holder
- ORION CORPORATION
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Region Midtjylland
- Sponsor organisation
- Region Midtjylland
- Address
- Palle Juul-Jensens Boulevard 99
- City
- Aarhus N
- Postcode
- 8200
- Country
- Denmark
Scientific contact point
- Organisation
- Region Midtjylland
- Contact name
- Claus Højbjerg Gravholt
Public contact point
- Organisation
- Region Midtjylland
- Contact name
- Claus Højbjerg Gravholt
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Aarhus Universitet ORG-100028380
|
Aarhus N, Denmark | On site monitoring |
Region Midtjylland
- Sponsor organisation
- Region Midtjylland
- Address
- Palle Juul-Jensens Boulevard 99
- City
- Aarhus N
- Postcode
- 8200
- Country
- Denmark
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 100 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2021-11-29 | 2021-11-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2019-004934-40 | 5 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_ICF controls | 2 |
| Subject information and informed consent form (for publication) | L1_ICF patients | 2 |
| Subject information and informed consent form (for publication) | L1_ICF_biobank controls | 3 |
| Subject information and informed consent form (for publication) | L1_ICF_biobank patients | 3 |
| Subject information and informed consent form (for publication) | L1_SIS controls | 2 |
| Subject information and informed consent form (for publication) | L1_SIS patients | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Divigel | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Estrofem | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-18 | Denmark | Acceptable 2024-10-01
|
2024-10-08 |