Effect of Rapamycin in Ovarian Aging

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Rapamycin in Ovarian Aging

Conditions
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Perimenopausal

Intervention / Treatment
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* Drug: Rapamycin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 38-45 years In the menopausal transition stage -3a Have been 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 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

Ages Eligible for Study
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Minimum Age: 38 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of Ovarian Reserve | Ovarian reserve will be determined using transvaginal ultrasound (TVUS). | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AMH level | Anti-müllerian hormone (AMH) levels will be measured. | Day 21 of menstrual cycle | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perimenopause, Premenopausal, Fertility, Women's health