Clinical Trials Nct Page

Summary
EudraCT Number:2022-003866-19
Sponsor's Protocol Code Number:83336
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2023-04-15
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2022-003866-19
A.3Full title of the trial
The effect of low-dose rhythmic 17-β-estradiol administration on bone turnover in postmenopausal women
Het effect van een lage dosis transdermaal 17-β-estradiol met ritmische toediening op botturnover markers bij postmenopauzale vrouwen
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Rhythmic estradiol and bone health (REBEL study)
Ritmisch oestrogeen en botgezondheid (REBEL studie)
A.3.2Name or abbreviated title of the trial where available
REBEL
A.4.1Sponsor's protocol code number83336
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorAmsterdam UMC location AMC
B.1.3.4CountryNetherlands
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportAmsterdam UMC
B.4.2CountryNetherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationAmsterdam UMC location AMC, Department of Endocrinology and Metabolism
B.5.2Functional name of contact pointAmsterdam UMC location AMC, Departm
B.5.3 Address:
B.5.3.1Street AddressMeibergdreef 9
B.5.3.2Town/ cityAmsterdam
B.5.3.3Post code1105AZ
B.5.3.4CountryNetherlands
B.5.4Telephone number31205666071
B.5.6E-maile.m.speksnijder@amsterdamumc.nl
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name estradiol
D.2.1.2Country which granted the Marketing AuthorisationBelgium
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Transdermal patch
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPTransdermal use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name estradiol
D.2.1.2Country which granted the Marketing AuthorisationNetherlands
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form Transdermal patch
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPTransdermal use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name uterogestan
D.2.1.2Country which granted the Marketing AuthorisationNetherlands
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.4Pharmaceutical form
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Osteoporosis prevention
E.1.1.1Medical condition in easily understood language
Prevention of osteoporosis
Voorkomen van botontkalking
E.1.1.2Therapeutic area Body processes [G] - Bones and nerves physological processes [G11]
MedDRA Classification
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To investigate the effect of low-dose rhythmic transdermal 17-β-estradiol on serum P1NP (marker of bone formation) and CTX (marker for bone resorption), versus continuous low-dose and standard-dose continuous transdermal 17-β-estradiol administration.
E.2.2Secondary objectives of the trial
1. To assess the effect of low-dose rhythmic transdermal 17-β-estradiol on fasting glucose, fasting insulin, insulin resistance (HOMA-IR), and post-OGTT glucose and insulin, versus continuous low-dose and standard-dose continuous transdermal 17-β-estradiol.
2. To assess the effect of low-dose rhythmic transdermal 17-β-estradiol on liver steatosis (CAP score), versus continuous low-dose and standard-dose continuous transdermal 17-β-estradiol.
3. To assess the effect of low-dose rhythmic transdermal 17-β-estradiol versus continuous low-dose and standard-dose continuous transdermal 17-β-estradiol on sleep quality.
4. In a subgroup: To assess the effect of low-dose rhythmic transdermal 17-β-estradiol versus continuous low-dose and standard-dose continuous transdermal 17-β-estradiol on 17-β-estradiol transcriptional regulation in adipose tissue.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
- Postmenopausal, defined as final menstrual cycle more than 12 months prior to
inclusion and FSH>30 IU/L
- Final menstrual cycle < 10 years prior to inclusion
- Age 45-60 years
E.4Principal exclusion criteria
• Contra-indication for estrogen and/or progesterone therapy: Presence or suspicion or history of breast cancer, endometrial cancer, ovarian cancer, presence or history of venous thromboembolism, arterial thrombosis (e.g. myocardial infarction, angina pectoris) inherited or acquired thrombophilia, presence of liver disease, untreated endometrial hyperplasia, abnormal vaginal bleeding, porphyria, uncontrolled or severe hypertension)
• First-grade family member with inherited thrombophilia or history of VTE under the age of 60 years
• Hysterectomy
• Premature menopause (menopause age <40 years)
• Known hypersensitivity to the excipients in the estradiol patch: acrylate copolymer, polyethylene terephthalate, α-tocopherol, soy allergy or peanut allergy (component of progesterone capsule)
• Hormonal contraception or hormone replacement therapy use (estradiol with or without progesterone) in the past 12 months
• Presence or history of any clinically relevant metabolic, endocrinological, hepatic, renal, cardiovascular, gastrointestinal, or respiratory conditions, history of bone disease or bone marrow disease, known vitamin D deficiency (25-OH vitamin D <30 nmol/L)
• Recent fracture (<12 months)
• BMI <20 or BMI ≥30
• Use of drugs including herbal medicine known to affect bone metabolism (e.g. corticosteroids) or to interfere with cytochrome P450 enzyme (CYP) pathways. Exceptions are occasional use of paracetamol, ibuprofen, acetylsalicylic acid or topical medication
• For adipose tissue biopsy: anticoagulant treatment, allergy to lidocaine
E.5 End points
E.5.1Primary end point(s)
The endpoint is the interaction between treatment and time on serum P1NP levels. (Does the change over time differ between the treatment arms?)
E.5.1.1Timepoint(s) of evaluation of this end point
Every two weeks in from baseline until week 16
E.5.2Secondary end point(s)
1. The secondary endpoint is the interaction between treatment and time on serum CTX levels. (Does the change over time differ between the treatment arms?)
2. Change in fasting glucose, fasting insulin, insulin resistance (HOMA-IR), and 2 hours post-OGTT glucose and insulin in relation to baseline after 16 weeks of treatment.
3. Change in liver steatosis (CAP score) in relation to baseline after 16 weeks of treatment.
4. Sleep quality (PSQI) and chronotype (MCTQ) and menopausal symptoms (GCS) after 16 weeks in relation to baseline.
5. In a subgroup: To assess the effect of low-dose rhythmic transdermal 17-β-estradiol versus continuous low-dose and standard-dose continuous transdermal 17-β-estradiol on 17-β-estradiol transcriptional regulation in adipose tissue using ChipSeq and RNA seq analysis (hypothesis-generating)..
E.5.2.1Timepoint(s) of evaluation of this end point
1. Every two weeks in from baseline until week 16
2. At baseline and after 16 weeks
3. At baseline and after 16 weeks
4. At baseline and after 16 weeks
5. At baseline and after 16 weeks
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety No
E.6.5Efficacy No
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
prevention osteoporosis
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) Yes
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial3
E.8.3 The trial involves single site in the Member State concerned Yes
E.8.4 The trial involves multiple sites in the Member State concerned No
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Last participants' last visit
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months
E.8.9.1In the Member State concerned days
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 48
F.1.3Elderly (>=65 years) No
F.2 Gender
F.2.1Female Yes
F.2.2Male No
F.3 Group of trial subjects
F.3.1Healthy volunteers Yes
F.3.2Patients No
F.3.3Specific vulnerable populations No
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception No
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state48
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Subjects may continue treatment under treatment care of their general practictioner. If they wish to do so, they may continue the treatment for a maximum of 5 years (from the start of treatment)
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-05-01
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-03-27
P. End of Trial
P.End of Trial StatusOngoing

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