Low‑dose oral contraceptives plus resistant starch for metabolic health in PCOS

Resistant Starch Usage in Polycystic Ovary Syndrome: Impact on Cardiometabolic Dysfunction and the Gut Microbiome (CORS-PCOS)

This study will test whether adding resistant starch to standard low‑dose oral contraceptives improves cardiometabolic markers and the gut microbiome in overweight women aged 18–40 with PCOS.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 40 Years
• Sex: Female
• Sponsor: University of Pennsylvania (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06852365 on ClinicalTrials.gov

What this trial studies

Adult women with PCOS and BMI 25–48 kg/m² will start low‑dose combined oral contraceptives and be randomized to 12 weeks of a resistant starch supplement or a placebo. Investigators will measure cardiometabolic parameters such as insulin sensitivity, lipids, and blood pressure and will analyze changes in gut microbiome composition before and after the intervention. Eligibility is defined by Rotterdam criteria for PCOS, including chronic anovulation, hyperandrogenism, and/or polycystic ovarian morphology or elevated AMH. Supplements include resistant starch formulations (e.g., wheat dextrin) with a maltodextrin placebo, and all visits take place at the University of Pennsylvania.

Who should consider this trial

Good fit: Women aged 18–40 with BMI between 25 and 48 kg/m² who meet Rotterdam criteria for PCOS (chronic anovulation, hyperandrogenism, and/or polycystic ovaries) are ideal candidates.

Not a fit: Women who are normal weight, outside the 18–40 age range, pregnant or breastfeeding, or taking other medications that affect metabolism may not benefit from or be eligible for this intervention.

Why it matters

Potential benefit: If successful, adding a simple resistant starch supplement to oral contraceptive therapy could improve insulin resistance, lipid profiles, and gut microbiome health in women with PCOS.

How similar studies have performed: Prior small clinical and mechanistic studies of dietary fibers and resistant starches have shown improvements in insulin sensitivity and gut microbiota, but evidence specifically in PCOS is limited.

Eligibility criteria

Inclusion Criteria:

1. Women between ages of 18-40 years with BMI greater than or equal to 25 kg/m² to less than or equal to 48 kg/m² diagnosed with PCOS defined by the Rotterdam criteria based on a history of chronic anovulation (8 or fewer periods), androgen excess \[defined as total serum testosterone, free testosterone or a FAI greater than or equal to 90% of the upper limit of normal) or hirsutism (Ferriman-Gallwey score greater than 6 for Hispanics/ Black and greater than or equal to 2 for women of Asian descent)\] and polycystic ovaries as defined by a pelvic ultrasound (20 or more follicles or ovarian vol greater than 10cm3) or elevated AMH.
2. For women with more regular bleeding patterns, but who are suspected to be experiencing periodic anovulatory bleeding, a midluteal progesterone (P4) level less than 3ng/dL will be evidence of ovulatory dysfunction and qualify as anovulation.
3. Women with only hyperandrogenic PCOS phenotype (hyperandrogenism + one more criteria) will be included to decrease the heterogeneity of the cohort and as metabolic risks are increased in these women compared to normo-androgenic women with PCOS.
4. Subjects should be willing to avoid pregnancy for the entire duration of the study.

Exclusion Criteria:

1. Subjects with other causes for irregular menses such as pregnancy, lactation, untreated hypothyroidism, untreated hyperprolactinemia and premature menopause.
2. Subjects with late onset adrenal hyperplasia
3. Subjects with history of bariatric surgery
4. Those who are unable to comply with the study procedures, for instance due to mental illness, substance abuse, or participation in other studies.
5. Subjects taking medications that affect weight or metabolic parameters (e.g. lipid lowering medications).
6. History of Crohn's disease and ulcerative colitis as well as current use of probiotics and laxatives are excluded.
7. Subjects could not have taken antibiotics for at least 3 months prior to randomization visit.
8. Subjects with greater than 20 g/day of dietary fiber intake based on pre-screening ASA-24 survey will be excluded.
9. Subjects with medical conditions that are contraindications to use of OCP and other medical conditions such as:

   1. Type 1 or 2 diabetes
   2. liver disease or dysfunctional liver (AST/ALT greater than 2x normal or a total bilirubin greater than 2.5 mg/dL)
   3. renal disease (BUN greater than 30 mg/dL or serum creatinine greater than 1.4 mg/dL)
   4. severe anemia (hemoglobin less than 10 mg/dL)
   5. alcohol abuse
   6. poorly controlled hypertension
   7. TG greater than 250 mg/dl
   8. chronic inflammatory conditions such as psoriasis
   9. history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident; known heart disease (New York Heart Association Class II or higher)
   10. history of cervical carcinoma, endometrial carcinoma, or breast carcinoma, adrenal or ovarian tumor secreting androgens, and Cushing's syndrome -

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Study coordinator: Anuja Dokras, MD PhD

Conditions Metabolic Syndrome; Polycystic Ovary Syndrome