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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Yolanda Smith, M.D., University of Michigan
ClinicalTrials.gov Identifier:
NCT00670800
First received: April 30, 2008
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Polycystic Ovary Syndrome
Drug: Metformin

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Mu-opioid Binding Potential Measured in Left Nucleus Accumbens [ Time Frame: Baseline and after 4 months ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 14
Study Start Date: January 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Normal Controls
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.
Experimental: PCOS Affected Women-Metformin Treatment
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.
Drug: Metformin
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.
Other Name: Glucophage

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.

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

Ages Eligible for Study:   21 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670800

Locations
United States, Michigan
University of Michigan, Michigan Clinical Research Unit
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Yolanda R Smith, MD, MS University of Michigan, Obstetrics and Gynecology
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yolanda Smith, M.D., Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT00670800     History of Changes
Other Study ID Numbers: 2276, HUM00008330
Study First Received: April 30, 2008
Results First Received: January 2, 2013
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
Polycystic Ovary Syndrome
Insulin resistance
Metformin
Brain function

Additional relevant MeSH terms:
Insulin Resistance
Polycystic Ovary Syndrome
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014