Polycystic Ovary SyndromePCOSNCT00868140
Effects of Pioglitazone on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)
A study testing pioglitazone in people with Polycystic Ovary Syndrome, run by Virginia Commonwealth University at 2 sites in 2 countries.
Trial summary
Our hypothesis is that hyperinsulinemia increases the renal clearance of D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS) and that this leads to a reduction in circulating insulin-stimulated D-chiro-inositol-containing inositol phosphoglycan (DCI-IPG) release. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Feb 2009to Aug 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult
Who may be able to join
- Obese (Body Mass Index or BMI greater than or equal to 30 kg/m2) women with PCOS between 18-40 years of age:
- oligomenorrhea (less than 8 menstrual periods annually)
- biochemical hyperandrogenemia (elevated total or free testosterone)
- normal thyroid function tests and serum prolactin; AND
- exclusion of 21a-hydroxylase deficiency by a fasting 17a-hydroxyprogesterone less than 200 ng/dl.51,
- acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (Complete Blood Chemistry or CBC, Comprehensive Metabolic Panel denoted SMA20, urinalysis, negative pregnancy test).
- Signed, witnessed informed consent.
- Ability to comply with study requirements.
Who cannot join
- Diabetes mellitus by fasting glucose or oral glucose tolerance test (OGTT), or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
- Current use of oral contraceptives.
- Documented or suspected recent (within one year) history of drug abuse or alcoholism.
- Ingestion of any investigational drug within two months prior to study onset.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Virginia Commonwealth University General Clinical Research Center
Richmond, Virginia, 23298
About this study
Official title: Determination if Indirectly Reducing Circulating Insulin by Improving Insulin Sensitivity With Pioglitazone Reduces Renal Clearance of D-chiro-inositol (DCI) Increases the Circulating Concentration of DCI and Enhances Insulin-stimulated Release of the D-chiro-inositol-containing Inositolphosphoglycan (DCI-IPG) Mediator in Obese Women With PCOS
Our hypothesis is that hyperinsulinemia increases the renal clearance of D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS) and that this leads to a reduction in circulating insulin-stimulated D-chiro-inositol-containing inositol phosphoglycan (DCI-IPG) release. To assess the effects of a chronic reduction in circulating insulin on DCI metabolism, we propose to reduce circulating insulin in obese women with PCOS by improving insulin sensitivity with the drug pioglitazone. Pioglitazone is a thiazolidinedione that improves peripheral insulin sensitivity, presumably by activation of the peroxisome proliferator-activated receptor gamma (PPARγ) receptor. Administration of pioglitazone to women with PCOS has been shown to improve insulin sensitivity, reduce insulin secretion, and decrease both fasting and post-prandial serum insulin concentrations.
Read the detailed description
This protocol focuses on the hypothesis that a deficiency in a putative inositolphosphoglycan (IPG) mediator of insulin action, namely a D-chiro-inositol-containing IPG (DCI-IPG), contributes to the insulin resistance of some women with PCOS. Our interest in this area stems directly from our previous studies, which demonstrated that administration of the precursor, D-chiro-inositol (DCI), to both obese and lean women with PCOS improved glucose intolerance while reducing circulating insulin, and simultaneously improved ovulatory function and decreased serum androgens. These findings were recently confirmed in a large-scale study by an independent group. The findings of these three studies suggested that administration of DCI improved insulin sensitivity in PCOS, which then resulted in an improved hormonal and metabolic milieu.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- pioglitazone, Placebo
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pioglitazoneDrug
pioglitazone 45 mg
PlaceboDrug
placebo daily
| Study group | Role | What they receive |
|---|---|---|
| 1/Pioglitazone | Experimental | Pioglitazone in pill form at 45mg twice per day for 6 months Receives: Drug: pioglitazone |
| 2/Placebo | Placebo comparator | Placebo control to arm 1 in pill form identical to treatment form also twice per day for 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC DCI-IPG (%/Min)
Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT before treatment with pioglitazone or placebo. Values reported as a percentage of bioactivity measured at time 0. Negative values indicate a decrease relative to the time 0 measurement.
Measured: Baseline
AUC DCI-IPG (%/Min)
Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT following 6 months of treatment with pioglitazone or placebo. Values reported as a percentage of bioactivity measured at time 0. Negative values indicate a decrease relative to the time 0 measurement.
Measured: 6 months
Fasting Serum Insulin
Fasting serum insulin (uIU.min/ml) measured at 0, 60 and 120 minutes of a 2 hour OGTT before treatment with either pioglitazone or placebo
Measured: baseline
Fasting Serum Insulin (uIU/ml)
Fasting serum insulin (uIU.min/ml) measured at 0, 60 and 120 minutes of a 2 hour OGTT following 6 months treatment with either pioglitazone or placebo
Measured: 6 months
Secondary outcomes (2)
Matsuda Index
Whole body insulin sensitivity as determined by the Matsuda Index as calculated using the following formula:
10,000 divided by the square root of (FPI* FPG) * (xGPC* xIPC) Where FPI is fasting plasma insulin expressed as uU/ml, FPG is fasting plasma glucose expressed as mg/dL, xGPC is mean plasma glucose concentration after the load and xIPC is the mean insulin concentration after the load.
Values calculated on samples taken at 0, 30, 60, 90 and 120 minutes of a 2 hour OGTT. Values typically range from 0 to 12 units with higher scores indicating better insulin sensitivity. A value of 2.5 or less is indicative of insulin resistance.
Measured: Baseline
Matsuda Index
Whole body insulin sensitivity as determined by the Matsuda Index
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionJun 2011
- Study completionAug 2011
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John E. Nestler, M.D., Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00868140
- Sponsor's protocol ID
- VCUIRB4480
- Other IDs
- GCRC0824
- Acronym
- PCOS
- Status last verified
- May 2016
- First submitted
- 22 Mar 2009
- Last updated
- 10 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: individual data kept confidential, secured and not shared beyond authorized study staff
Publications
Gupta A, Jakubowicz D, Nestler JE. Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome. Metab Syndr Relat Disord. 2016 Oct;14(8):391-396. doi: 10.1089/met.2016.0009. Epub 2016 Mar 30.
PubMed 27028341
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination if Indirectly Reducing Circulating Insulin by Improving Insulin Sensitivity With Pioglitazone Reduces Renal Clearance of D-chiro-inositol (DCI) Increases the Circulating Concentration of DCI and Enhances Insulin-stimulated Release of the D-chiro-inositol-containing Inositolphosphoglycan (DCI-IPG) Mediator in Obese Women With PCOS
- ClinicalTrials.gov ID
- NCT00868140
- Acronym / sponsor ID
- PCOS / VCUIRB4480
- Conditions
- Polycystic Ovary Syndrome
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Jun 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 24 Mar 2009 (estimated)
- Results
- Posted 10 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Our hypothesis is that hyperinsulinemia increases the renal clearance of D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS) and that this leads to a reduction in circulating insulin-stimulated D-chiro-inositol-containing inositol phosphoglycan (DCI-IPG) release. To assess the effects of a chronic reduction in circulating insulin on DCI metabolism, we propose to reduce circulating insulin in obese women with PCOS by improving insulin sensitivity with the drug pioglitazone. Pioglitazone is a thiazolidinedione that improves peripheral insulin sensitivity, presumably by activation of the peroxisome proliferator-activated receptor gamma (PPARγ) receptor. Administration of pioglitazone to women with PCOS has been shown to improve insulin sensitivity, reduce insulin secretion, and decrease both fasting and post-prandial serum insulin concentrations.
Detailed description
This protocol focuses on the hypothesis that a deficiency in a putative inositolphosphoglycan (IPG) mediator of insulin action, namely a D-chiro-inositol-containing IPG (DCI-IPG), contributes to the insulin resistance of some women with PCOS. Our interest in this area stems directly from our previous studies, which demonstrated that administration of the precursor, D-chiro-inositol (DCI), to both obese and lean women with PCOS improved glucose intolerance while reducing circulating insulin, and simultaneously improved ovulatory function and decreased serum androgens. These findings were recently confirmed in a large-scale study by an independent group. The findings of these three studies suggested that administration of DCI improved insulin sensitivity in PCOS, which then resulted in an improved hormonal and metabolic milieu.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/Pioglitazone | Experimental | Drug: pioglitazonePioglitazone in pill form at 45mg twice per day for 6 months |
| 2/Placebo | Placebo comparator | Drug: PlaceboPlacebo control to arm 1 in pill form identical to treatment form also twice per day for 6 months |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Obese (Body Mass Index or BMI greater than or equal to 30 kg/m2) women with PCOS between 18-40 years of age:
- acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (Complete Blood Chemistry or CBC, Comprehensive Metabolic Panel denoted SMA20, urinalysis, negative pregnancy test).
- Signed, witnessed informed consent.
- Ability to comply with study requirements.
Key exclusion criteria (4 listed)
- Diabetes mellitus by fasting glucose or oral glucose tolerance test (OGTT), or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
- Current use of oral contraceptives.
- Documented or suspected recent (within one year) history of drug abuse or alcoholism.
- Ingestion of any investigational drug within two months prior to study onset.
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 |
|---|---|---|
| pioglitazonepioglitazone 45 mg | Drug | 1/Pioglitazone |
| Placeboplacebo daily | Drug | 2/Placebo |
Primary outcome
AUC DCI-IPG (%/Min)
Time frame: Baseline
Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT before treatment with pioglitazone or placebo. Values reported as a percentage of bioactivity measured at time 0. Negative values indicate a decrease relative to the time 0 measurement.
AUC DCI-IPG (%/Min)
Time frame: 6 months
Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT following 6 months of treatment with pioglitazone or placebo. Values reported as a percentage of bioactivity measured at time 0. Negative values indicate a decrease relative to the time 0 measurement.
Fasting Serum Insulin
Time frame: baseline
Fasting serum insulin (uIU.min/ml) measured at 0, 60 and 120 minutes of a 2 hour OGTT before treatment with either pioglitazone or placebo
Fasting Serum Insulin (uIU/ml)
Time frame: 6 months
Fasting serum insulin (uIU.min/ml) measured at 0, 60 and 120 minutes of a 2 hour OGTT following 6 months treatment with either pioglitazone or placebo
2 secondary outcomes
Matsuda Index
Time frame: Baseline
Matsuda Index
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27028341Gupta A, Jakubowicz D, Nestler JE. Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome. Metab Syndr Relat Disord. 2016 Oct;14(8):391-396. doi: 10.1089/met.2016.0009. Epub 2016 Mar 30.
- Individual participant dataSharing planned: No. individual data kept confidential, secured and not shared beyond authorized study staff
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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.
John E. Nestler, M.D. principal investigator
Virginia Commonwealth University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing pioglitazone in people with Polycystic Ovary Syndrome, run by Virginia Commonwealth University at 2 sites in 2 countries.
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 8 inclusion and 4 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: stopped early, as of the sponsor's last update on 10 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Venezuela. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 10 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
AUC DCI-IPG (%/Min) (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00868140, which also lists 1 linked publication.
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 10 Jun 2016.