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Rhythmic Estradiol and Bone Health (REBEL)

Primary Purpose

Osteoporosis Risk, Menopause

Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Estradiol patch
Progesterone
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Osteoporosis Risk

Eligibility Criteria

45 Years - 60 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria: Postmenopausal, defined as final menstrual cycle more than 1 years prior to inclusion and FSH>30 IU/L Final menstrual cycle < 10 years prior to inclusion Exclusion Criteria: Contra-indication for estrogen and/or progesterone therapy First-grade family member with inherited thrombophilia or history of venous thromboembolism under the age of 60 years Hysterectomy Premature menopause (menopause age <40 years) Known hypersensitivity to the excipients in the estradiol patch or 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

Sites / Locations

  • Amsterdam UMCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Experimental

Arm Label

Continuous estradiol 50 mcg/day

Continuous estradiol 25 mcg/day

Rhythmic estradiol 25-50 mcg/day

Arm Description

The continuous standard-dose 17-β-estradiol group will receive the standard therapy for prevention of osteoporosis. A transdermal patch that releases 50ug/24 hrs of 17-β-estradiol will be administered continuously during the 16 weeks of treatment.

The continuous low-dose 17-β-estradiol group will receive a transdermal patch that releases 25ug/24 hrs of 17-β-estradiol administered continuously during the 16 weeks of treatment.

The rhythmic 17-β-estradiol group will receive a transdermal patch for two weeks that releases 25ug/24hrs of 17-β-estradiol, and a patch of 50ug/24hrs for 2 weeks in each 4-week cycle.

Outcomes

Primary Outcome Measures

Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP
Serum P1NP
The interaction between treatment and time on serum P1NP

Secondary Outcome Measures

Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX
Serum CTX
The interaction between treatment and time on serum CTX

Full Information

First Posted
May 15, 2023
Last Updated
August 26, 2023
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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1. Study Identification

Unique Protocol Identification Number
NCT05903820
Brief Title
Rhythmic Estradiol and Bone Health
Acronym
REBEL
Official Title
The Effect of Low-dose Rhythmic 17-β-estradiol Administration on Bone Turnover in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 19, 2023 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this randomized-controlled trial is to compare the effect of rhythmic estrogen treatment to continuous estrogen treatment on bone turnover in healthy postmenopausal women. The main question it aims to answer are: • Does rhythmic estrogen lead to increased bone formation in healthy postmenopausal women, compared to continuous estrogen? Participants will receive one of the following treatments for a duration of 16 weeks: - Rhythmic estradiol: Alternating 4-week cycles consisting of transdermal 17-β-estradiol 25μg/24hrs for two weeks, followed by two weeks of transdermal 17-β-estradiol 50μg/24hrs. Estradiol therapy will be combined with continuous oral micronized progesterone 100mg once daily. Low-dose continuous estradiol: Continuous transdermal 17-β-estradiol 25μg/24hrs, combined with continuous oral micronized progesterone 100mg daily once daily. Standard-dose continuous estradiol: Continuous transdermal 17-β-estradiol 50μg/24hrs, combined with continuous oral micronized progesterone 100mg daily once daily. If there is a comparison group: Researchers will compare rhythmic estradiol to continuous estradiol to see if rhythmic estradiol improves bone formation in postmenopausal women.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis Risk, Menopause

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Continuous estradiol 50 mcg/day
Arm Type
Active Comparator
Arm Description
The continuous standard-dose 17-β-estradiol group will receive the standard therapy for prevention of osteoporosis. A transdermal patch that releases 50ug/24 hrs of 17-β-estradiol will be administered continuously during the 16 weeks of treatment.
Arm Title
Continuous estradiol 25 mcg/day
Arm Type
Active Comparator
Arm Description
The continuous low-dose 17-β-estradiol group will receive a transdermal patch that releases 25ug/24 hrs of 17-β-estradiol administered continuously during the 16 weeks of treatment.
Arm Title
Rhythmic estradiol 25-50 mcg/day
Arm Type
Experimental
Arm Description
The rhythmic 17-β-estradiol group will receive a transdermal patch for two weeks that releases 25ug/24hrs of 17-β-estradiol, and a patch of 50ug/24hrs for 2 weeks in each 4-week cycle.
Intervention Type
Drug
Intervention Name(s)
Estradiol patch
Other Intervention Name(s)
transdermal17-beta-estradiol
Intervention Description
Transdermal patch of estradiol
Intervention Type
Drug
Intervention Name(s)
Progesterone
Other Intervention Name(s)
micronized progesterone
Intervention Description
Oral progesterone capsules 100mg/day
Primary Outcome Measure Information:
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 2 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 4 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 6 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 8 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 10 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 12 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 14 weeks
Title
Serum P1NP
Description
The interaction between treatment and time on serum P1NP
Time Frame
The difference in P1NP between treatment arms after 16 weeks
Secondary Outcome Measure Information:
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 2 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 4 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 6 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 8 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 10 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 12 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX treatment arms after 14 weeks
Title
Serum CTX
Description
The interaction between treatment and time on serum CTX
Time Frame
The difference in CTX between treatment arms after 16 weeks
Other Pre-specified Outcome Measures:
Title
Fasting glucose
Description
Change in fasting glucose
Time Frame
The difference between treatment arms in terms of change in fasting glucose after 16 weeks
Title
Fasting insulin
Description
Change in fasting insulin
Time Frame
The difference between treatment arms in terms of change in fasting insulin after 16 weeks
Title
Fasting insulin insulin resistance (HOMA-IR), and post-OGTT outcomes from to baseline until 16 weeks of treatment.
Description
Change in fasting insulin
Time Frame
The difference between treatment arms in terms of change in HOMA-IR after 16 weeks
Title
Glucose levels after an oral glucose tolerance test (OGTT)
Description
Change in glucose levels 2 hours after an oral glucose tolerance test (OGTT)
Time Frame
The difference between treatment arms in terms of change in post-OGTT glucose values after 16 weeks
Title
Change in liver steatosis
Description
Controlled Attenuation Parameter (CAP) scores, assessed with a Fibroscan
Time Frame
The difference between treatment arms in terms of change in CAP scores after 16 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Postmenopausal, defined as final menstrual cycle more than 1 years prior to inclusion and FSH>30 IU/L Final menstrual cycle < 10 years prior to inclusion Exclusion Criteria: Contra-indication for estrogen and/or progesterone therapy First-grade family member with inherited thrombophilia or history of venous thromboembolism under the age of 60 years Hysterectomy Premature menopause (menopause age <40 years) Known hypersensitivity to the excipients in the estradiol patch or 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
M
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter M Bisschop
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Esther M Speksnijder
Phone
+31 20 5666071
Email
e.m.speksnijder@amsterdamumc.nl
First Name & Middle Initial & Last Name & Degree
Peter H Bisschop
First Name & Middle Initial & Last Name & Degree
Esther M Speksnijder

12. IPD Sharing Statement

Plan to Share IPD
No

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Rhythmic Estradiol and Bone Health

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