PCOS (Polycystic Ovary Syndrome) of Bilateral OvariesPhase 3RESTORENCT05819853
Role of Semaglutide in Restoring Ovulation in Youth and Adults With Polycystic Ovary Syndrome
A Phase 3 study testing Semaglutide Injectable Product (Wegovy and/or Ozempic) in people with PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries and Obese, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 35 years, women only
- Conditions the study is for
- PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Obese
- What is being tested?
- Semaglutide Injectable Product (Wegovy and/or Ozempic)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2023to 30 Jun 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 35 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Female
- Ages 12-35 years
- Sedentary- less than 2 hours of moderate (jogging, swimming etc.) exercise a week.
- Oligomenorrhea, on or off metformin, as defined per age category in the most recent 2018 PCOS international guidelines
- Initial BMI based on age and weight:
- If <18 years, initial BMI percentile ≥95
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- 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
- Must be weight stable within ±5kg in the 3 months prior to enrollment
- 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
- 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.
- 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
Who cannot join
- 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
- 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.
- Weight loss medications in the last 6 months
- Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
- Severe illness requiring hospitalization within 60 days.
- Diabetes, defined as Hemoglobin A1C ≥6.5%
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- Anemia, defined as Hemoglobin < 12 mg/dL
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Colorado Anschutz/Children's Hospital Colorado Aurora
Aurora, Colorado, 80045
Yesenia Garcia Reyes, 720-777-6984, PCOSresearch@cuanschutz.edu
About this study
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.
Read the 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.
- Being tested
- Semaglutide Injectable Product (Wegovy and/or Ozempic)
- Keywords
- PCOS, semaglutide
- Medical subject headings
- Polycystic Ovary Syndrome, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Injectable Product (Wegovy and/or Ozempic)Drug
Also called Semaglutide (Wegovy and/or Ozempic)
10 months of semaglutide, with dose escalation as recommended by manufacturer. Maximum dose used will be 1.7mg
| Study group | Role | What they receive |
|---|---|---|
| Untreated PCOS | Experimental | 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. Receives: Drug: Semaglutide Injectable Product (Wegovy and/or Ozempic) |
| PCOS on Metformin | Experimental | 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. Receives: Drug: Semaglutide Injectable Product (Wegovy and/or Ozempic) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ovulation frequency before and after semaglutide in females with PCOS
The change in ovulation will be measured at baseline and 6-10 months post treatment with semaglutide from 4 months daily urinary progesterone metabolites
Measured: 14 months
Secondary outcomes (2)
Change in Whole Body Insulin Sensitivity
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.
Measured: Baseline and 10 months
Change in ovarian morphology
Participants will have an ovarian ultrasound performed to measure change in ovarian morphology: ovarian size and number of follicles pre/post treatment with semaglutide
Measured: Baseline and 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2023
- Study start3 Nov 2023
- Primary completion1 Feb 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PCOS (Polycystic Ovary Syndrome) of Bilateral OvariesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Melanie Cree-Green, MD,PhD, Principal investigator, University of Colorado Anschutz/Children's Hospital Colorado
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05819853
- Sponsor's protocol ID
- 21-4941
- Other IDs
- R01HD108340
- Acronym
- RESTORE
- Status last verified
- Aug 2026
- First submitted
- 6 Apr 2023
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No