Inositol Supplementation to Treat PCOS (INSUPP-PCOS) (INSUPP-PCOS)

Inositol Supplementation to Treat Polycystic Ovary Syndrome: A Double Blind Dose Ranging RCT (INSUPP-PCOS)

To determine if Inositol, a dietary supplement, will improve ovarian and adrenal androgen excess in women with Polycystic Ovarian Syndrome(PCOS).

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome; Hyperandrogenism; Insulin Resistance; Glucose Intolerance; Anovulation; Metabolic Complication
• Intervention / Treatment: Other: Placebo; Drug: Inositol

Detailed Description

This trial will test prospectively the effects of inositol supplementation in a dose ranging double blind randomized controlled trial, according to CONSORT guidelines. This will be a four armed study of three doses of inositol vs. placebo over a three month period with the reduction in hyperandrogenism (based on serum testosterone levels) as the primary outcome and key secondary outcomes of the change in sex hormone binding globulin(SHBG) and the related free androgen index, fasting insulin levels and area under the curve glucose levels from an oral glucose challenge test (OGTT). The hypothesis is that women with PCOS who receive inositol supplementation will have a dose related reduction in hyperandrogenism. Further, we propose that the primary mechanism of inositol will be a significant improvement in hyperandrogenism (both ovarian and adrenal) vs. placebo, as documented by a lower free androgen index [decreased total testosterone and increased sex hormone blinding globulin (SHBG)], lower sebum measures and lower antral follicle counts of the ovary and anti-Mullerian hormone, all of which will correlate with the decrease in hyperandrogenism.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with chronic anovulation or oligomenorrhea defined as spontaneous intermenstrual periods of greater than or equal to 45 days or a total of less than or equal to 8 menses per year.
• Women with Hyperandrogenism defined as a total testosterone greater than 50 ng/dL or a free androgen index greater than 10.
• Women with Polycystic Ovaries on Ultrasound defined as either 12 or more follicles measuring 2-9 mm in diameter or increased ovarian volume greater than 10 cm.

Exclusion Criteria:

• Women with Hyperprolactinemia defined as 2 prolactin levels at least one week apart greater than 30 ng/mL.
• Women with known 21-hydroxylase deficiency or other enzyme deficiency leading to the congenital adrenal hyperplasia.
• Women with elevated FSH levels greater than 10 mIU/mL.
• Women with uncorrected thyroid disease as per ASRM guidelines for nonpregnant subjects (TSH less than 0.45 mIU/mL or greater than 4.5 MIU/mL).
• Women with a suspected adrenal or ovarian tumor secreting androgens
• Women with Cushing's syndrome
• Women on confounding medications which affect ovarian function including metformin, hormonal contraceptives or other medications for type 2 diabetes
• Women with medical conditions that are contraindications to OTC inositol or previous allergic reactions to the supplement or to the placebo maltodextrin or inulin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Treatment bid; Women with PCOS (N = 30) will receive the daily placebo (maltodextrin and inulin) in an identical fashion as the active study group and will be monitored the same.	Other: Placebo; Placebo; Other Names: maltodextrin and inulin
Experimental: Active Treatment with Inositol 1gm/bid; Women with PCOS (N = 30) will receive daily inositol powder BID as active drug (each dose with 1000 mg of myo-inositol and 25 mg of d-chiro-inositol) over the initial 3 mos RCT period.	Drug: Inositol; 1gm/bid, 2gm/bid or 3gm/bid of Inositol powder
Experimental: Active Treatment with Inositol 2 gm/bid; Women with PCOS (N = 30) will receive daily inositol powder BID as active drug (each dose with 2000 mg of myo-inositol and 50 mg of d-chiro-inositol) over the initial 3 mos RCT period.	Drug: Inositol; 1gm/bid, 2gm/bid or 3gm/bid of Inositol powder
Experimental: Active Treatment with Inositol 3 gm/bid; Women with PCOS (N = 30) will receive daily inositol powder BID as active drug (each dose with 3000 mg of myo-inositol and 75 mg of d-chiro-inositol) over the initial 3 mos RCT period.	Drug: Inositol; 1gm/bid, 2gm/bid or 3gm/bid of Inositol powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total testosterone	Serum total testosterone levels	baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SHBG	SHBG levels	baseline and 3 months
Change in Free Androgen Index (FAI)	FAI levels	baseline and 3 months
Change in area under the curve (AUC) of glucose	AUC of a 2-hour 75g glucose tolerance test, which measures glucose at 0, 30, 60, 90, and 120 minutes.	baseline and 3 months
Change in fasting insulin	Fasting insulin levels	baseline and 3 months

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Richard S. Legro, M.D., Penn State College of Medicine, Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2020
• Primary Completion (Actual): December 10, 2025
• Study Completion (Actual): December 10, 2025

Study Registration Dates

• First Submitted: March 4, 2019
• First Submitted That Met QC Criteria: March 4, 2019
• First Posted (Actual): March 6, 2019

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Insulin Resistance; Polycystic Ovary Syndrome; Glucose Intolerance; Anovulation; Hyperandrogenism; Metabolic Complication
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Neoplasms; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Genital Diseases, Female; Glucose Metabolism Disorders; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Congenital Abnormalities; Hyperinsulinism; Ovarian Cysts; Cysts; Disorders of Sex Development; Urogenital Abnormalities; Hyperglycemia; 46, XX Disorders of Sex Development; Adrenogenital Syndrome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Polycystic Ovary Syndrome; Insulin Resistance; Glucose Intolerance; Hyperandrogenism; Anovulation; Organic Chemicals; Dietary Carbohydrates; Carbohydrates; Polymers; Macromolecular Substances; Alcohols; Polysaccharides; Starch; Glucans; Biopolymers; Fructans; Sugar Alcohols; Inositol; maltodextrin; Inulin
• Other Study ID Numbers: Study00010252; 1R01AT009484-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No