Effect of Rapamycin in Ovarian Aging (Rapamycin)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Perimenopausal
• Intervention / Treatment: Drug: Rapamycin; Other: Placebo

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapamycin; Participants randomized to the treatment arm will receive 5mg/week of rapamycin orally, for 12 weeks (3 months).	Drug: Rapamycin; 5mg/week of rapamycin orally for 12 weeks
Placebo Comparator: Placebo; Participants randomized to the placebo arm will receive placebo orally, for 12 weeks (3 months).	Other: Placebo; 5mg/week of placebo orally for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Ovarian Reserve	Ovarian reserve will be determined using AMH	Up to 1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Samuel Z. Williams, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Actual): October 21, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 17, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Fertility; Premenopausal; Perimenopause; Women's health
• Additional Relevant MeSH Terms: Organic Chemicals; Macrolides; Lactones; Sirolimus
• Other Study ID Numbers: AAAU1074

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No