Clinical trial NCT05836025: Effect of Rapamycin in Ovarian Aging
Official title: Effect of Rapamycin in Ovarian Aging
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Perimenopausal
Keywords: Premenopausal
Perimenopause
Fertility
Women's health
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2023-05-01
Enrollment: 50
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Measure of Ovarian Reserve
timeFrame: Up to 1 year
Secondary outcomes:
measure: TVU
timeFrame: Up to 1 year
measure: Estradiol (E2) Level
timeFrame: Day 21 of menstrual cycle
measure: FSH Level
timeFrame: Day 21 of menstrual cycle
measure: Klotho Level
timeFrame: Day 21 of menstrual cycle
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center / NewYork-Presbyterian Hospital
state: New York
Study officials:
affiliation: Columbia University
name: Samuel Z. Williams, MD
role: PRINCIPAL_INVESTIGATOR
References: