Polycystic Ovary SyndromeNCT00670800

Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome

A study testing Metformin in people with Polycystic Ovary Syndrome, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 21 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for: Polycystic Ovary Syndrome
What is being tested?: Metformin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: Jan 2008to Aug 2009
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 21 to 40 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Insulin-resistant PCOS (Arm: PCOS Affected Women)
Irregular menstrual cycle (Arm: PCOS Affected Women)
Hyperandrogenism (Arm: PCOS Affected Women)
Regular menstrual cycles (Arm: Normal Controls)
Normal hormonal levels (Arm: Normal Controls)
Lack of hirsutism (Arm: Normal Controls)
Acne-free (Arm: Normal Controls)
Candidates are BMI-matched and screened for insulin resistance prior to inclusion. (Arm: Normal Controls)

Who cannot join

Left handedness
Acute medical illness
Uncorrected thyroid disease
Diabetes renal
Cardiac or pulmonary insufficiency
Active liver disease

Show all 17Show fewer

Neurological disease
Current psychiatric illness
Claustrophobia
Contraindications to MRI
Smoking
Use of hormones
Centrally acting or insulin sensitizing mediations
Allergy to any opioid medication
Substance abuse
Pregnancy
BMI >35.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan, Michigan Clinical Research Unit
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome

The purpose of this study is to evaluate the effects of insulin resistance on brain function in women with Polycystic Ovary Syndrome (PCOS). PCOS affected women will be evaluated prior to and following 4-month treatment with Metformin. Additionally, brain function in women with PCOS will be compared to the brain activity in normal control subjects with regular menstrual cycles.

Read the detailed description

The pathogenesis of Polycystic Ovary Syndrome (PCOS), a reproductive and metabolic disorder, is associated with insulin resistance. The effects of insulin resistance on cognition, mood, opioid system and reproductive function in PCOS affected women are investigated in the current study. The identification of reversible changes in brain function and reproductive measures in insulin resistant PCOS patients would likely significantly influence treatment protocols for these young women.

Evaluate the differences in opioid tone in women with insulin resistant PCOS compared to normal controls.
Evaluate whether an oral hypoglycemic agent is capable of altering opioid tone in women with insulin resistant PCOS.

Conditions: Polycystic Ovary Syndrome
Being tested: Metformin
Keywords: Polycystic Ovary Syndrome, Insulin resistance, Metformin, Brain function
Medical subject headings: Polycystic Ovary Syndrome, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MetforminDrug
Also called Glucophage
Following the baseline studies, PCOS affected women will be initiated on metformin at a dose of 500 mg orally after breakfast and the dose will be increased the following week to 500 mg twice daily (BID), adding a dose after lunch. On the third week, the dose will be increased to 500 mg three times daily (TID), adding a 500 mg tablet after supper. All subjects will be monitored for possible side effects such as nausea, vomiting, diarrhea, anorexia, and abdominal discomfort. These side effects tend to be mild, dose-related and improve with continued use of metformin. Hypoglycemia is rare and tends to occur in the setting of alcohol abuse or prolonged starvation. Malabsorption of vitamin B12 and folate occurs with long-term treatment, although it usually does not lead to anemia.

Study groups in NCT00670800
Study group	Role	What they receive
Normal Controls	No intervention	Control subjects will have 5 visits (screening, oral glucose tolerance test (OGTT), neuropsychological testing, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) as they will receive no treatment and will not have repeat studies. The baseline values obtained from the control subjects will be compared to the baseline values acquired from the PCOS affected subjects.
PCOS Affected Women-Metformin Treatment	Experimental	Subjects with Polycystic Ovary Syndrome (PCOS) will be scheduled for 9 visits total: following the screening visit they will go through OGTT, neuro-psychological testing, fMRI and PET scan before and after 4 months of metformin use: 500mg tablets once daily with breakfast for 1 week, then increased to one tablet twice daily with breakfast \& lunch for 1 week, then increased to one tablet three times daily with breakfast, lunch \& dinner. Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

Mu-opioid Binding Potential Measured in Left Nucleus Accumbens
Mu-opioid binding potential in left nucleus accumbens is measured before and after 4 months of Metformin treatment.
Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment.
Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Control group was measured at baseline only.
Measured: Baseline and after 4 months
Mu-opioid Binding Potential Measured in Right Nucleus Accumbens
Mu-opioid binding potential in right nucleus accumbens measured before and after 4 months of Metformin treatment.
Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment.
Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Control group was measured at baseline only.
Measured: Baseline and after 4 months
Mu-opioid Binding Potential Measured in Left Amygdala
Mu-opioid binding potential in left amygdala measured before and after 4 months of Metformin treatment.
Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment.
Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Measured: Baseline and after 4 months
Mu-opioid Binding Potential Measured in Right Amygdala
Mu-opioid binding potential in right amygdala measured before and after 4 months of Metformin treatment.
Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment.
Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Control group was measured at baseline only.
Measured: Baseline and 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Aug 2009

First posted2 May 2008 (estimated)
Study startJan 2008
Primary completionAug 2009
Study completionAug 2009

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 (2)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 University of MichiganThe 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: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00670800
Sponsor's protocol ID: 2276
Other IDs: HUM00008330
Status last verified: May 2014
First submitted: 30 Apr 2008
Last updated: 21 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Berent-Spillson A, Love T, Pop-Busui R, Sowers M, Persad CC, Pennington KP, Eyvazaddeh AD, Padmanabhan V, Zubieta JK, Smith YR. Insulin resistance influences central opioid activity in polycystic ovary syndrome. Fertil Steril. 2011 Jun 30;95(8):2494-8. doi: 10.1016/j.fertnstert.2011.03.031. Epub 2011 Apr 12.
PubMed 21486668
Marsh CA, Berent-Spillson A, Love T, Persad CC, Pop-Busui R, Zubieta JK, Smith YR. Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: a case-control pilot study. Fertil Steril. 2013 Jul;100(1):200-7.e1. doi: 10.1016/j.fertnstert.2013.02.054. Epub 2013 Apr 1.
PubMed 23557757

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Efficacy of Ovarian Drilling Via vNOTES Laparoscopy in Patients With PCOS
PCOS (Polycystic Ovary Syndrome)
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingObservational study
The Value of LC-MS/MS Detection of Androgen Profiles in the Diagnosis of PCOS: A Prospective, Multicenter Real-world Study
Polycystic Ovary Syndrome (PCOS)
Recruiting
The Effects of the Mediterranean Diet and Synbiotics in Polycystic Ovary Syndrome
PCOS (Polycystic Ovary Syndrome)
Recruiting
Brown Adipose Tissue Modulation in Polycystic Ovary Syndrome Using Infrared Thermography
Polycystic Ovary Syndrome (PCOS)

All Polycystic Ovary Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 21 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome
ClinicalTrials.gov ID: NCT00670800
Acronym / sponsor ID: 2276
Conditions: Polycystic Ovary Syndrome
Keywords: Polycystic Ovary Syndrome, Insulin resistance, Metformin, Brain function
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: University of MichiganUniversity, hospital or other
Study start: Jan 2008
Primary completion: Aug 2009 (actual)
Study completion: Aug 2009 (actual)
First posted: 2 May 2008 (estimated)
Results: Posted 15 May 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Evaluate the differences in opioid tone in women with insulin resistant PCOS compared to normal controls.
Evaluate whether an oral hypoglycemic agent is capable of altering opioid tone in women with insulin resistant PCOS.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Normal Controls	No intervention	–Control subjects will have 5 visits (screening, oral glucose tolerance test (OGTT), neuropsychological testing, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) as they will receive no treatment and will not have repeat studies. The baseline values obtained from the control subjects will be compared to the baseline values acquired from the PCOS affected subjects.
PCOS Affected Women-Metformin Treatment	Experimental	Drug: MetforminSubjects with Polycystic Ovary Syndrome (PCOS) will be scheduled for 9 visits total: following the screening visit they will go through OGTT, neuro-psychological testing, fMRI and PET scan before and after 4 months of metformin use: 500mg tablets once daily with breakfast for 1 week, then increased to one tablet twice daily with breakfast \& lunch for 1 week, then increased to one tablet three times daily with breakfast, lunch \& dinner.

Who may qualify

Ages: 21 to 40 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Insulin-resistant PCOS (Arm: PCOS Affected Women)
Irregular menstrual cycle (Arm: PCOS Affected Women)
Hyperandrogenism (Arm: PCOS Affected Women)
Regular menstrual cycles (Arm: Normal Controls)
Normal hormonal levels (Arm: Normal Controls)

Key exclusion criteria (17 listed)

Left handedness
Acute medical illness
Uncorrected thyroid disease
Diabetes renal
Cardiac or pulmonary insufficiency

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
MetforminAlso: GlucophageFollowing the baseline studies, PCOS affected women will be initiated on metformin at a dose of 500 mg orally after breakfast and the dose will be increased the following week to 500 mg twice daily (BID), adding a dose after lunch. On the third week, the dose will be increased to 500 mg three times daily (TID), adding a 500 mg tablet after supper. All subjects will be monitored for possible side effects such as nausea, vomiting, diarrhea, anorexia, and abdominal discomfort. These side effects tend to be mild, dose-related and improve with continued use of metformin. Hypoglycemia is rare and tends to occur in the setting of alcohol abuse or prolonged starvation. Malabsorption of vitamin B12 and folate occurs with long-term treatment, although it usually does not lead to anemia.	Drug	PCOS Affected Women-Metformin Treatment

Primary outcome

Mu-opioid Binding Potential Measured in Left Nucleus Accumbens
Time frame: Baseline and after 4 months
Mu-opioid binding potential in left nucleus accumbens is measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Mu-opioid Binding Potential Measured in Right Nucleus Accumbens
Time frame: Baseline and after 4 months
Mu-opioid binding potential in right nucleus accumbens measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.
Mu-opioid Binding Potential Measured in Left Amygdala
Time frame: Baseline and after 4 months
Mu-opioid binding potential in left amygdala measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.)
Mu-opioid Binding Potential Measured in Right Amygdala
Time frame: Baseline and 4 months
Mu-opioid binding potential in right amygdala measured before and after 4 months of Metformin treatment. Mu-opioid binding potential is measured in vivo with C11-carfentanil positron emission tomography in women with PCOS before and after 4 months of metformin treatment. Binding Potential is measured by the ratio of Mu-opioid receptor concentration (Bmax)/Receptor radiotracer (C11-carfentanil) affinity (Kd.) Control group was measured at baseline only.

Results and safety

Results posted to the registry on 15 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Women Affected With PCOS - Metformin	7	7
Women Controls Without PCOS	7	5

Primary outcome: Mu-opioid Binding Potential Measured in Left Nucleus Accumbens

Time frame: Baseline and after 4 months. Mean (Standard Deviation). Unit: ratio

Measure	PCOS Affected Women Pre-Metformin (Baseline) n = 7	PCOS Affected Women Post-Metformin (After 4 Months) n = 7	Normal Controls n = 5
Value	1.95 (0.17)	1.65 (.27)	1.53 (0.28)

PCOS Affected Women Pre-Metformin (Baseline) vs Normal Controls: p = 0.143, t-test, 2 sided
PCOS Affected Women Post-Metformin (After 4 Months) vs Normal Controls: p = 0.900, t-test, 2 sided
PCOS Affected Women Pre-Metformin (Baseline) vs PCOS Affected Women Post-Metformin (After 4 Months): p = 0.133, t-test, 2 sided

Population analysed: All 7 PCOS women completed the protocol and were included. 5 of 7 controls were included in this analysis. 2 controls were excluded from analysis because repeat baseline OGTT showed HOMA %S of \<80%.

Primary outcome: Mu-opioid Binding Potential Measured in Right Nucleus Accumbens

Time frame: Baseline and after 4 months. Mean (Standard Deviation). Unit: ratio

Measure	PCOS Affected Women Pre-Metformin (Baseline) n = 7	PCOS Affected Women Post-Metformin (After 4 Months) n = 7	Normal Control Women n = 5
Value	2.40 (.11)	2.11 (0.21)	2.05 (0.28)

PCOS Affected Women Pre-Metformin (Baseline) vs Normal Control Women: p = 0.049, t-test, 2 sided
PCOS Affected Women Post-Metformin (After 4 Months) vs Normal Control Women: p = 0.717, t-test, 2 sided
PCOS Affected Women Pre-Metformin (Baseline) vs PCOS Affected Women Post-Metformin (After 4 Months): p = 0.038, t-test, 2 sided

Population analysed: All 7 PCOS women were included, 2 controls were excluded because repeat baseline HOMA2-IR %S was \<80%.

Primary outcome: Mu-opioid Binding Potential Measured in Left Amygdala

Time frame: Baseline and after 4 months. Mean (Standard Deviation). Unit: ratio

Measure	PCOS Affected Women Pre-Metformin (Baseline) n = 7	PCOS Affected Women Post-Metformin (After 4 Months) n = 7	Normal Controls n = 5
Value	2.28 (.17)	2.08 (.19)	2.03 (.07)

PCOS Affected Women Pre-Metformin (Baseline) vs Normal Controls: p = 0.498, t-test, 2 sided
PCOS Affected Women Post-Metformin (After 4 Months) vs Normal Controls: p = 0.835, t-test, 2 sided
PCOS Affected Women Pre-Metformin (Baseline) vs PCOS Affected Women Post-Metformin (After 4 Months): p = 0.606, t-test, 2 sided

Primary outcome: Mu-opioid Binding Potential Measured in Right Amygdala

Time frame: Baseline and 4 months. Mean (Standard Deviation). Unit: ratio

Measure	PCOS Affected Women Pre-Metformin (Baseline) n = 7	PCOS Affected Women Post-Metformin (After 4 Months) n = 7	Normal Controls n = 5
Value	2.28 (.23)	2.11 (.22)	2.06 (.26)

PCOS Affected Women Pre-Metformin (Baseline) vs Normal Controls: p = 0.118, t-test, 2 sided
PCOS Affected Women Post-Metformin (After 4 Months) vs Normal Controls: p = 0.581, t-test, 2 sided
PCOS Affected Women Pre-Metformin (Baseline) vs PCOS Affected Women Post-Metformin (After 4 Months): p = 0.190, t-test, 2 sided

Adverse events

Time frame: Adverse events were followed in the course of 2 years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Normal Controls	0 of 5 (0%)	1 of 5 (20%)	Not reported
PCOS Affected Women on Metformin	0 of 7 (0%)	1 of 7 (14.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21486668Berent-Spillson A, Love T, Pop-Busui R, Sowers M, Persad CC, Pennington KP, Eyvazaddeh AD, Padmanabhan V, Zubieta JK, Smith YR. Insulin resistance influences central opioid activity in polycystic ovary syndrome. Fertil Steril. 2011 Jun 30;95(8):2494-8. doi: 10.1016/j.fertnstert.2011.03.031. Epub 2011 Apr 12.
Derived from this study: PubMed 23557757Marsh CA, Berent-Spillson A, Love T, Persad CC, Pop-Busui R, Zubieta JK, Smith YR. Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: a case-control pilot study. Fertil Steril. 2013 Jul;100(1):200-7.e1. doi: 10.1016/j.fertnstert.2013.02.054. Epub 2013 Apr 1.

Related trials for Polycystic Ovary Syndrome

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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.

Yolanda R Smith, MD, MS principal investigator

University of Michigan, Obstetrics and Gynecology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Metformin in people with Polycystic Ovary Syndrome, run by University of Michigan 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 8 inclusion and 17 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 21 May 2014. 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?

Yes. Results are posted in the registry (first posted 15 May 2014). 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?

Mu-opioid Binding Potential Measured in Left Nucleus Accumbens (time frame: Baseline and after 4 months). 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 NCT00670800, which also lists 2 linked publications.

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 21 May 2014.