Using Semaglutide to Restore Ovulation in Young Women with PCOS

Role of Semaglutide in Restoring Ovulation in Youth and Adults With Polycystic Ovary Syndrome

This study is testing if a medication called semaglutide can help young women with PCOS and obesity start ovulating again.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 12 Years to 35 Years
• Sex: Female
• Sponsor: University of Colorado, Denver (Academic / other)
• Locations: 1 site (Aurora, Colorado)
• Trial ID: NCT05819853 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on restoring ovulation in girls and women aged 12-35 with obesity and polycystic ovary syndrome (PCOS). Participants will undergo a 10-month intervention after an initial 4-month observation period, during which their metabolic changes, weight loss, and reproductive function will be closely monitored. The study aims to explore the relationship between weight loss and reproductive health, as well as identify predictors of response to the treatment based on hormonal and metabolic measures.

Who should consider this trial

Good fit: Ideal candidates are females aged 12-35 with obesity and diagnosed PCOS who are sedentary and not on hormonal contraception.

Not a fit: Patients who are not diagnosed with PCOS or those who are on hormonal contraception may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve reproductive health and metabolic outcomes for young women suffering from PCOS.

How similar studies have performed: Other studies have shown promising results with glucagon-like peptide-1 receptor agonists in metabolic and reproductive health, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria

1. Female
2. Ages 12-35 years
3. Sedentary- less than 2 hours of moderate (jogging, swimming etc.) exercise a week.
4. Oligomenorrhea, on or off metformin, as defined per age category in the most recent 2018 PCOS international guidelines
5. Initial BMI based on age and weight:

   1. If \<18 years, initial BMI percentile ≥95
   2. If 18-35 years, initial BMI ≥30 kg/m2 OR initial BMI ≥27 kg/m2 with at least one weight-related comorbid condition, e.g., hypertension or dyslipidemia
   3. Must be weight stable within ±5kg in the 3 months prior to enrollment
6. Diagnosed with PCOS per the most stringent NIH criteria with adaptation for adolescents (oligomenorrhea \>24 months post-menarche or primary amenorrhea after age 15 years and clinical/ biochemical hypertestosteronemia
7. Participants cannot be on hormonal contraception, so participants should remain abstinent or use reliable non-hormonal contraception (e.g., copper IUD) for the entire study period. For participants who receive semaglutide, they should avoid pregnancy for at least 2 months after stopping medication to avoid fetal exposure to the medication.
8. For participants in the metformin + semaglutide group, participants must have been stable on ≥ 1500 mg of metformin a day for at least 3 months by time of screening

Exclusion Criteria:

1. Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Family history of medullary thyroid cancer or thyroid nodule palpated by endocrinologist at screening. - Per approved drug label
2. Use of medications known to affect insulin sensitivity: metformin (cannot have been used in the 3 months prior to screening for the untreated arm of the study), chronic oral steroids, oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, estrogen-containing hormonal contraception (cannot have been used in the 6 months prior to screening), progesterone-containing hormonal contraception (cannot have been used in the 3 months prior to screening). Dermal patch or vaginal ring contraception methods. Weight loss medications or stimulants. Use of other products containing other GLP-1 agonists.
3. Weight loss medications in the last 6 months
4. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
5. Severe illness requiring hospitalization within 60 days.
6. Diabetes, defined as Hemoglobin A1C ≥6.5%
7. Anemia, defined as Hemoglobin \< 12 mg/dL
8. Diagnosed major psychiatric or developmental disorder limiting informed consent.

10\) Known liver disease other than NAFLD, or AST or ALT \>125 IU/L. 11) Personal history of pancreatitis 12) Known renal disease of any severity or an eGFR at screening of \<45ml/min/1.73m2 13) History of severe GI disease (e.g., gastroparesis) 14) History of gallstones 15) Untreated thyroid disease 16) History of hypersensitivity to semaglutide 17) Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma).

18\) Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder 19) Desiring pregnancy in the next 12-18 months. 20) Bariatric surgery 21) Use of THC (smoking or edible) more than 3 days a week 22) Alcohol use-drinking more than 2 drinks, more than 3 days a week 23) Any potential participants who cannot/will not commit to abstinence, use of a copper intrauterine device (IUD), or use of double barrier forms of contraception.

Where this trial is running

Aurora, Colorado

• University of Colorado Anschutz/Children's Hospital Colorado Aurora — Aurora, Colorado, United States (Recruiting)

Study contacts

• Principal investigator: Melanie Cree-Green, MD,PhD — University of Colorado Anschutz/Children's Hospital Colorado
• Study coordinator: Yesenia Garcia-Reyes, MS

Conditions PCOS of Bilateral Ovaries; Obese; PCOS; semaglutide