An interventional study of Weight loss in Polycystic Ovary Syndrome and Obesity, sponsored by Virginia Commonwealth University. Completed at 1 site in United States. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-03-30.
Sponsored by Virginia Commonwealth University · Not applicable, Interventional, and Treatment
The polycystic ovary syndrome is the leading cause of female infertility in the United States. The disorder affects approximately 6-10% of women of reproductive age. It is widely accepted that "insulin resistance" may be responsible for the infertility of this syndrome. Women are insulin resistant when their bodies do not respond to insulin's action to handle sugar as they normally should. Because of this insulin resistance, women with the polycystic ovary syndrome are also at high risk for developing type 2 diabetes. We have previously shown that D-chiro-inositol (DCI), a substance naturally found in our body that helps insulin's action, is lacking in women with the polycystic ovary syndrome. Not having enough DCI may lead to insulin resistance. The purpose of this study is to determine if weight loss helps to replenish the body with DCI and help to promote insulin's action.
Insulin resistance is present in women with PCOS. Women with PCOS are at high risk for developing type 2 diabetes, presumably due to the insulin resistance that accompanies the syndrome. Some actions of insulin may be effected by putative inositolphosphoglycan (IPG) mediators of insulin action, and evidence suggests that a deficiency in a specific D-chiro-inositol (DCI)-containing IPG may contribute to insulin resistance in individuals with impaired glucose tolerance or type 2 diabetes mellitus. A deficiency in DCI may also contribute to the insulin resistance in women with PCOS. In PCOS, three separate studies have shown that administration of DCI, the precursor to DCI-IPG, to women with PCOS improved glucose intolerance while reducing circulating insulin, improved ovulatory function, and decreased serum androgens. Serum triglycerides, HDL cholesterol and blood pressure improved in some of the studies as well. Collectively, these findings strongly suggest that administration of DCI improved insulin sensitivity in women with PCOS, and that a deficiency in DCI may contribute to the insulin resistance of this disorder.
Previous studies of our group demonstrated that women with PCOS, when compared to normal women, had a (i) greater than 5-fold increase in the renal clearance of DCI, (ii) 50% reduction in the circulating concentration of DCI, and (iii) decreased insulin-stimulated release of DCI-IPG during an oral glucose tolerance test (OGTT). Moreover, insulin sensitivity (as determined by frequently sampled intravenous glucose tolerance test [FSIVGTT]) correlated inversely with renal clearance of DCI. In addition, it appears that obesity needs to be present for the abnormality in renal clearance of DCI to be present in PCOS, and obesity does not seem to have an effect in DCI renal clearance in normal women.
Our hypothesis is that obesity modulates the renal clearance of DCI in women with PCOS, but not in normal women. A corollary of this hypothesis is that an increased urinary DCI clearance leads to a reduction in circulating DCI and insulin-stimulated DCI-IPG release, and aggravates insulin resistance in women with PCOS. To test our hypothesis, we propose to study the following specific aims:
Specific Aims:
Specific Aim 1: Determine if DCI renal clearance in obese women with PCOS is increased compared to age- and weight-matched, obese normal women.
In this aim, we will determine if obese women with PCOS have (i) increased renal clearance of DCI, (ii) decreased circulating levels of DCI, and (iii) decreased DCI-IPG release in blood during an OGTT, as compared to age- and BMI-matched, obese normal women.
Specific Aim 2: Determine if weight loss reduces DCI renal clearance in obese women with PCOS, but not in age- and weight-matched obese normal women.
This aim determines if weight loss reverses the abnormalities in DCI handling in PCOS. The effects of weight loss on (i) renal clearance of DCI, (ii) circulating levels of DCI, and (iii) DCI-IPG release in blood during an OGTT, will be compared between obese women with PCOS and age- and BMI-matched obese normal women.
Specific Aim 3: Determine if a change (reduction) in DCI renal clearance as a result of weight loss is correlated with a change (improvement) in insulin sensitivity in obese women with PCOS that is independent of weight loss itself.
In our Preliminary Studies, we have determined that insulin sensitivity has a significant inverse relationship with urinary DCI clearance. In this aim, we will determine if decreasing DCI renal clearance by weight loss in obese women with PCOS will improve insulin sensitivity independent of the degree of weight loss (via statistical adjustment with the degree of weight loss as a covariate).
Specific Aim 4: Determine if an equivalent degree of weight loss in obese women with and without PCOS is associated with (i) a greater reduction in DCI renal clearance, and (ii) a greater improvement in insulin sensitivity in the PCOS women compared to the normal women.
To further demonstrate whether improvement in insulin sensitivity as a result of an improvement in DCI handling is independent of weight loss itself, women will be stratified by the degree of weight loss. For each degree of weight loss, we will determine if obese women with PCOS have (i) a greater reduction of renal clearance of DCI and (ii) a greater improvement in insulin sensitivity as a result of weight reduction, as compared to weight-matched obese normal women.
If our proposed studies confirm a role for obesity in modulating DCI handling in PCOS, they will substantially enhance our understanding of the pathogenesis of PCOS and are likely to provide insights into novel treatment strategies directed specifically at the IPG system and normalization of its function.
944 studies on the registry are indexed under Polycystic Ovary Syndrome; 174 are open to participants now.
This study's enrollment of 79 is above the median of 70 across 685 interventional studies indexed under Polycystic Ovary Syndrome.
Browse Polycystic Ovary Syndrome studies →Virginia Commonwealth University is the lead sponsor of 641 studies on the registry; 82 are open to participants now.
Of its 88 completed or terminated interventional studies of FDA-regulated products, 62 (70%) have results posted.
Counted across the registry records on this site, refreshed daily.
PCOS women only:
Normal women only:
All women:
Exclusion Criteria:
Normal women only:
PCOS women receiving weight loss intervention
Behavioral: Weight loss
Non-PCOS women receiving weight loss intervention
Behavioral: Weight loss
Insulin sensitivity (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Changes of Serum D-Chiro-Inositol (DCI) concentrations (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Changes of DCI renal clearance (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Changes of AUC insulin during OGTT (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
AUC of bioactive DCI-IPG during OGTT (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Ratio of AUC DCI-IPG to AUC insulin during OGTT (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Weight loss (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Serum Myo-Inositol (Myo) concentrations (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
MYO bioactivity (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
Serum inflammatory and cardiovascular markers (Change from baseline to 8 weeks)
Time frame: Baseline to 8 weeks
This study is completed, as verified in Mar 2018. You cannot join it, but the record below documents what was studied.
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