Inositol Supplementation to Treat PCOS (INSUPP-PCOS)

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

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.

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

Conditions
-----------------
Polycystic Ovary Syndrome, Anovulation, Hyperandrogenism, Insulin Resistance, Glucose Intolerance, Metabolic Complication

Intervention / Treatment
-----------------
* Other: Placebo
* Drug: Inositol


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo Group; Active Treatment with Inositol 1gm/bid; Active Treatment with Inositol 2gm/bid; Active Treatment with Inositol 3gm/ bid
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Treatment bid<br>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<br>* Placebo<br>* Other names: maltodextrin and inulin;|
| Experimental: Active Treatment with Inositol 1gm/bid<br>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<br>* 1gm/bid, 2gm/bid or 3gm/bid of Inositol powder<br>|
| Experimental: Active Treatment with Inositol 2 gm/bid<br>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<br>* 1gm/bid, 2gm/bid or 3gm/bid of Inositol powder<br>|
| Experimental: Active Treatment with Inositol 3 gm/bid<br>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<br>* 1gm/bid, 2gm/bid or 3gm/bid of Inositol powder<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polycystic Ovary Syndrome, Anovulation, Hyperandrogenism, Insulin Resistance, Glucose Intolerance, Metabolic Complication