Effect of Rapamycin in Ovarian Aging

Phase 2

Active, not recruiting

• Conditions: Perimenopausal
• Interventions: Other: Placebo; Drug: Rapamycin

• Registration Number: NCT05836025
• Lead Sponsor: Columbia University

Brief Summary

The investigators are proposing a prospective, randomized, double-blind, placebo-controlled pilot study assessing the ability of low-dose rapamycin to delay ovarian aging in women. Animal studies have shown the potential of rapamycin in slowing or reversing some age-associated pathways.

Detailed Description

One of the earliest and most profound changes associated with human aging is the rapid decline in ovarian follicular activity and reproductive capacity. Beginning around age 35, fertility rates decline as the number and quality of oocytes fall, culminating in the onset of menopause around age 51. The onset of menopause has profound socioeconomic, quality of life, and health implications, including increasing the risks of cardiovascular disease, osteoporosis, cognitive decline and dementia. While human lifespan has increased, the age of menopause has remained largely unchanged, leaving more women living an ever-larger proportion of their lives in a postmenopausal state. The narrow reproductive window adds socioeconomic pressure on women to complete childbearing within a limited timeframe, or preserve their fertility with egg or embryo freezing. The investigators and others have demonstrated that rapamycin can delay ovarian aging in mice.

The purpose of this pilot study is to determine whether the same may be true in humans. Extending the reproductive lifespan will reduce the time pressure on women to complete childbearing and will allow more women to spend more of their lives in the premenopausal status and delay the negative healthy consequences of menopause.

Study Timeline

• Study First Submitted: 2023-04-17
• Study First Submitted QC: 2023-04-17
• Study First Posted: 2023-05-01
• Study Start: 2023-06-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-03
• Last Update Posted: 2025-01-06
• Primary Completion: 2025-10
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 50

Inclusion Criteria

• Women aged 35-45 years
• In the menopausal transition stage -3a
• Have been unable to conceive based on diminished ovarian reserve and who have failed to develop any euploid embryos with IVF or who do not desire to conceive within the next 1.5 years
• Have regular menstrual periods (with less than 7 days of variability)
• Early follicular phase follicle stimulating hormone (FSH) levels ] < 20 mIU/mL
• Anti-müllerian hormone (AMH) levels of >0.1 ng/mL
• Antral Follicle Counts (AFC) of >3

Exclusion Criteria

• Women with irregular menstrual cycles
• Severe ovarian deficiency, or with no evidence of remaining follicles
• Kidney or liver disease
• Any significant medical disease, including cancer
• Contraindications to receiving rapamycin

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants randomized to the placebo arm will receive placebo orally, for 12 weeks (3 months).
Rapamycin	Rapamycin	Participants randomized to the treatment arm will receive 5mg/week of rapamycin orally, for 12 weeks (3 months).

Primary Outcome Measures

Name	Time	Method
Measure of Ovarian Reserve	Up to 1 year	Ovarian reserve will be determined using AMH

Secondary Outcome Measures

Name	Time	Method
Klotho Level	Day 21 of menstrual cycle	Klotho levels will be measured.
TVU	Up to 1 year	TVUs will be used to measure follicle growth
Estradiol (E2) Level	Day 21 of menstrual cycle	Estradiol levels will be measured.
FSH Level	Day 21 of menstrual cycle	Follicle stimulating hormone (FSH) levels will be measured.

Trial Locations

Locations (1)

Columbia University Irving Medical Center / NewYork-Presbyterian Hospital; 🇺🇸 New York, New York, United States