Rhythmic Estradiol and Bone Health

Menopause Clinical Trial

— REBEL  

Official title:

The Effect of Low-dose Rhythmic 17-β-estradiol Administration on Bone Turnover in Postmenopausal Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05903820
• Other study ID #: NL83336.018.23
• Status: Recruiting
• Phase: Phase 4
• Start date: July 19, 2023
• Est. completion date: September 2024

Study information

• Verified date: August 2023
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: M
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: September 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 45 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Menopause
• Osteoporosis
• Osteoporosis Risk

Intervention

Drug:
• Estradiol patch
Transdermal patch of estradiol
• Progesterone
Oral progesterone capsules 100mg/day

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fasting glucose	Change in fasting glucose	The difference between treatment arms in terms of change in fasting glucose after 16 weeks
Other	Fasting insulin	Change in fasting insulin	The difference between treatment arms in terms of change in fasting insulin after 16 weeks
Other	Fasting insulin insulin resistance (HOMA-IR), and post-OGTT outcomes from to baseline until 16 weeks of treatment.	Change in fasting insulin	The difference between treatment arms in terms of change in HOMA-IR after 16 weeks
Other	Glucose levels after an oral glucose tolerance test (OGTT)	Change in glucose levels 2 hours after an oral glucose tolerance test (OGTT)	The difference between treatment arms in terms of change in post-OGTT glucose values after 16 weeks
Other	Change in liver steatosis	Controlled Attenuation Parameter (CAP) scores, assessed with a Fibroscan	The difference between treatment arms in terms of change in CAP scores after 16 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 2 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 4 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 6 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 8 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 10 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 12 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 14 weeks
Primary	Serum P1NP	The interaction between treatment and time on serum P1NP	The difference in P1NP between treatment arms after 16 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 2 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 4 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 6 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 8 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 10 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 12 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX treatment arms after 14 weeks
Secondary	Serum CTX	The interaction between treatment and time on serum CTX	The difference in CTX between treatment arms after 16 weeks