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

NCT ID: NCT05819853

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-03
• Study Completion Date: 2028-06-30

Brief Summary

Girls and women 12-35 years old with obesity and polycystic ovarian syndrome who are on or off metformin, will receive a glucagon like peptide-1 receptor agonist intervention for 10 months to induce metabolic changes, weight loss and improve reproductive abnormalities.

Detailed Description

Polycystic ovary syndrome is one of the most common endocrinopathies in women, presents with anovulation in adolescence, and reproductive dysfunction is related to excess weight. After a 4-month observation period of either no medication or metformin treatment, females aged 12-35 years with obesity and polycystic ovary syndrome will receive 10 months of a glucagon-like peptide-1 receptor agonist to induce metabolic changes, weight loss and improve reproductive abnormalities. We will assess the relationship between weight loss and reproductive function, as well as identify if age, hormonal and metabolic measures and such insulin sensitivity and insulin secretion predict the response to glucagon-like peptide-1 receptor agonist therapy.

Conditions

PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries; Obese

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Untreated PCOS

Participants with PCOS who are not on metformin or hormonal therapy, will receive 10-months of semaglutide intervention.

Participants will get either semaglutide as either:

Wegovy: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and 1.7mg for the remainder of the study.

or

Ozempic: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and Wegovy for 1.7mg for the remainder of the study.

Group Type: EXPERIMENTAL

Semaglutide Injectable Product (Wegovy and/or Ozempic)

Intervention Type: DRUG

10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg

PCOS on Metformin

Participants with PCOS who are currently on metformin and still not having regular menses, will receive 10-months of semaglutide intervention. Participants in this arm will continue to take their metformin throughout the trial.

Participants will get either semaglutide as either:

Wegovy: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and 1.7mg for the remainder of the study.

or

Ozempic: 0.25mg for 4 weeks, 0.5mg for 4 weeks, 1mg 4-weeks, and Wegovy for 1.7mg for the remainder of the study.

Group Type: EXPERIMENTAL

Semaglutide Injectable Product (Wegovy and/or Ozempic)

Intervention Type: DRUG

10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg

Interventions

Semaglutide Injectable Product (Wegovy and/or Ozempic)

10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg

Intervention Type: DRUG

Other Intervention Names

Semaglutide (Wegovy and/or Ozempic)

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melanie Cree-Green, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado Anschutz/Children's Hospital Colorado

Locations

University of Colorado Anschutz/Children's Hospital Colorado Aurora

Aurora, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Yesenia Garcia-Reyes, MS

Role: CONTACT

PCOSresearch@cuanschutz.edu

720-777-6984

Facility Contacts

Yesenia Garcia Reyes

Role: primary

PCOSresearch@cuanschutz.edu

720-777-6984

Other Identifiers

R01HD108340

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-4941

Identifier Type: -

Identifier Source: org_study_id