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

Phase 3

Recruiting

• Conditions: PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries; Obese
• Interventions: Drug: Semaglutide Injectable Product (Wegovy and/or Ozempic)

• Registration Number: NCT05819853
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2023-04-06
• Study First Submitted QC: 2023-04-06
• Study First Posted: 2023-04-19
• Study Start: 2023-11-03
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-31
• Primary Completion: 2028-02-01
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 80

Inclusion Criteria

Not provided

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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).

11. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Untreated PCOS	Semaglutide Injectable Product (Wegovy and/or Ozempic)	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.
PCOS on Metformin	Semaglutide Injectable Product (Wegovy and/or Ozempic)	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.

Primary Outcome Measures

Name	Time	Method
Change in ovulation frequency before and after semaglutide in females with PCOS	14 months	The change in ovulation will be measured at baseline and 6-10 months post treatment with semaglutide from 4 months daily urinary progesterone metabolites

Secondary Outcome Measures

Name	Time	Method
Change in Whole Body Insulin Sensitivity	Baseline and 10 months	Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model using SAMM II software. This software uses participant weight, glucose and insulin concentrations at various time points during the oral glucose tolerance test to calculate the participant's insulin sensitivity. A positive Si value means an improvement in insulin sensitivity.
Change in ovarian morphology	Baseline and 10 months	Participants will have an ovarian ultrasound performed to measure change in ovarian morphology: ovarian size and number of follicles pre/post treatment with semaglutide

Trial Locations

Locations (1)

University of Colorado Anschutz/Children's Hospital Colorado Aurora; 🇺🇸 Aurora, Colorado, United States