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

Primary Purpose

Polycystic Ovary Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Metformin
Sponsored by
University of Michigan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome focused on measuring Polycystic Ovary Syndrome, Insulin resistance, Metformin, Brain function

Eligibility Criteria

21 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

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

Sites / Locations

  • University of Michigan, Michigan Clinical Research Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Normal Controls

PCOS Affected Women-Metformin Treatment

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
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.
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.)
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.

Secondary Outcome Measures

Full Information

First Posted
April 30, 2008
Last Updated
May 15, 2014
Sponsor
University of Michigan
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1. Study Identification

Unique Protocol Identification Number
NCT00670800
Brief Title
Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome
Official Title
Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
Keywords
Polycystic Ovary Syndrome, Insulin resistance, Metformin, Brain function

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Non-Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal Controls
Arm Type
No Intervention
Arm Description
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.
Arm Title
PCOS Affected Women-Metformin Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glucophage
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mu-opioid Binding Potential Measured in Left Nucleus Accumbens
Description
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.
Time Frame
Baseline and after 4 months
Title
Mu-opioid Binding Potential Measured in Right Nucleus Accumbens
Description
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.
Time Frame
Baseline and after 4 months
Title
Mu-opioid Binding Potential Measured in Left Amygdala
Description
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.)
Time Frame
Baseline and after 4 months
Title
Mu-opioid Binding Potential Measured in Right Amygdala
Description
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.
Time Frame
Baseline and 4 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: Left handedness Acute medical illness Uncorrected thyroid disease Diabetes renal Cardiac or pulmonary insufficiency Active liver disease 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yolanda R Smith, MD, MS
Organizational Affiliation
University of Michigan, Obstetrics and Gynecology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan, Michigan Clinical Research Unit
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21486668
Citation
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.
Results Reference
result
PubMed Identifier
23557757
Citation
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.
Results Reference
derived

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

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