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

• ClinicalTrials.gov Identifier: NCT05819853
• Recruitment Status: Recruiting
• First Posted: April 19, 2023
• Last Update Posted: April 17, 2024
• Sponsor: University of Colorado, Denver
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

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.

Condition or disease	Intervention/treatment	Phase
PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries; Obese	Drug: Wegovy Injectable Product; Drug: Metformin and Wegovy	Phase 3

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 Design

• Study Type: Interventional
• Estimated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Role of Semaglutide in Restoring Ovulation in Youth and Adults With Polycystic Ovary Syndrome
• Actual Study Start Date: November 3, 2023
• Estimated Primary Completion Date: February 1, 2028
• Estimated Study Completion Date: June 30, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Metformin + Semaglutide; Participants with PCOS who are currently on metformin and still not having regular menses, will receive 10-months of semaglutide intervention	Drug: Metformin and Wegovy; Participants already on Metformin as part of their clinical care, and still having irregular periods will be enrolled in the Metformin and Semaglutide arm. Semaglutide will be added in addition to the Metformin they are currently taking. 10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg; Other Name: Glucophage and Semaglutide
Experimental: Semaglutide; Participants with PCOS who are not on metformin or hormonal therapy, will receive 10-months of semaglutide intervention	Drug: Wegovy Injectable Product; 10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg; Other Name: Semaglutide

Outcome Measures

Primary Outcome Measures :

1. Rate of ovulation [ Time Frame: 60 months ]
   Number of ovulations as assessed by urinary progesterone in 4 month before and during treatment

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 35 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: PCOS is a condition only found in those of female sex
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Yesenia Garcia-Reyes, MS; 720-777-6984; PCOSresearch@cuanschutz.edu

Locations

United States, Colorado

University of Colorado Anschutz/Children's Hospital Colorado Aurora; Recruiting

Aurora, Colorado, United States, 80045

Contact: Yesenia Garcia Reyes 720-777-6984 PCOSresearch@cuanschutz.edu

Sponsors and Collaborators

University of Colorado, Denver

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

Investigators

• Principal Investigator: Melanie Cree-Green, MD,PhD; University of Colorado Anschutz/Children's Hospital Colorado

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT05819853
• Other Study ID Numbers: 21-4941; R01HD108340 ( U.S. NIH Grant/Contract )
• First Posted: April 19, 2023
• Last Update Posted: April 17, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Colorado, Denver:

PCOS; semaglutide

Additional relevant MeSH terms:

Polycystic Ovary Syndrome; Syndrome; Disease; Pathologic Processes; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Metformin; Semaglutide; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists