Polycystic Ovary SyndromeNCT00436865
Insulin and the Polycystic Ovary Syndrome--Weight Reduction Study
A study testing Weight loss in people with Polycystic Ovary Syndrome and Obesity, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome, Obesity
- What is being tested?
- Weight loss
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Obese (≥ 30 kg/m2) premenopausal women with PCOS and normal women between 18-40 years of age.
- PCOS women only:
- oligomenorrhea (<= 8 menstrual periods annually),
- biochemical hyperandrogenemia (elevated total or free testosterone),
- normal thyroid function tests and serum prolactin, and
- exclusion of 21alpha-hydroxylase deficiency by a fasting 17alpha-hydroxyprogesterone <200 ng/dl.
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- Normal women only:
- regular monthly menses, and
- normal serum total and free testosterone.
- All women:
- acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (CBC, SMA20, urinalysis),
- have not been dieting in the 3 months prior to study enrollment,
- signed, witnessed informed consent,
- ability to comply with study requirements.
Who cannot join
- Diabetes mellitus by fasting glucose or OGTT, or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
- Documented or suspected recent (within one year) history of drug abuse or alcoholism.
- Ingestion of any investigational drug within 3 months prior to study onset.
- Pregnancy as documented by urine hCG.
- PCOS women only: Change in PCOS medication regimen (oral contraceptives, spironolactone, insulin sensitizers) within 3 months prior to the start of the study.
- Normal women only:
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- history of gestational diabetes,
- positive family history for first-degree relative with diabetes,
- disorders linked to insulin resistance (hypertension or dyslipidemia),
- Use of oral or other systemic contraceptives, or spironolactone within 3 months prior to the start of the study,
- Use of medications (including OTC drugs) known to affect insulin sensitivity such as metformin, rosiglitazone, pioglitazone, niacin, corticosteroids, beta blockers, calcium channel blockers and thiazide diuretics within 3 months prior to the start of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University General Clinical Research Center
Richmond, Virginia, 23298
About this study
Official title: Insulin and the Polycystic Ovary Syndrome
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.
Read the detailed description
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.
- Conditions
- Polycystic Ovary Syndrome, Obesity
- Being tested
- Weight loss
- 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.
Weight lossBehavioural
| Study group | Role | What they receive |
|---|---|---|
| PCOS | Other | PCOS women receiving weight loss intervention Receives: Behavioral: Weight loss |
| Control | Other | Non-PCOS women receiving weight loss intervention Receives: Behavioral: Weight loss |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin sensitivity (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Changes of Serum D-Chiro-Inositol (DCI) concentrations (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Changes of DCI renal clearance (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Changes of AUC insulin during OGTT (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
AUC of bioactive DCI-IPG during OGTT (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Ratio of AUC DCI-IPG to AUC insulin during OGTT (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Secondary outcomes (4)
Weight loss (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Serum Myo-Inositol (Myo) concentrations (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
MYO bioactivity (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Serum inflammatory and cardiovascular markers (Change from baseline to 8 weeks)
Measured: Baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2007 (estimated)
- Study startFeb 2007
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Kai I. Cheang, Pharm.D., Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00436865
- Sponsor's protocol ID
- HM10313
- Other IDs
- K23HD049454-01A2
- Status last verified
- Mar 2018
- First submitted
- 15 Feb 2007
- Last updated
- 30 Mar 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin and the Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT00436865
- Acronym / sponsor ID
- HM10313
- Conditions
- Polycystic Ovary Syndrome, Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Feb 2007
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 19 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCOS | Other | Behavioral: Weight lossPCOS women receiving weight loss intervention |
| Control | Other | Behavioral: Weight lossNon-PCOS women receiving weight loss intervention |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Obese (≥ 30 kg/m2) premenopausal women with PCOS and normal women between 18-40 years of age.
- PCOS women only:
- Normal women only:
- All women:
Key exclusion criteria (11 listed)
- Diabetes mellitus by fasting glucose or OGTT, or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
- Documented or suspected recent (within one year) history of drug abuse or alcoholism.
- Ingestion of any investigational drug within 3 months prior to study onset.
- Pregnancy as documented by urine hCG.
- PCOS women only: Change in PCOS medication regimen (oral contraceptives, spironolactone, insulin sensitizers) within 3 months prior to the start of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Weight loss | Behavioural | Control, PCOS |
Primary outcome
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
4 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kai I. Cheang, Pharm.D. principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Weight loss in people with Polycystic Ovary Syndrome and Obesity, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin sensitivity (Change from baseline to 8 weeks) (time frame: Baseline to 8 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2018.