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

NCT00670800 | Completed Results

• 2 other identifiers: 2276HUM00008330
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycystic Ovary Syndrome

Keywords

Polycystic Ovary Syndrome; Insulin resistance; Metformin; Brain function

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.)

  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.

  Baseline and 4 months

Study Arms (2)

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.

Drug: Metformin

Interventions

Metformin DRUG

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.

Also known as: Glucophage

PCOS Affected Women-Metformin Treatment

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead

Study Sites (1)

University of Michigan, Michigan Clinical Research Unit

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (2)

• 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.

  PMID: 21486668 RESULT

• 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.

  PMID: 23557757 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance

Interventions

Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Yolanda Smith
• Organization: University of Michigan

ysmith@umich.edu

(734) 936-7401

Study Officials

• Yolanda R Smith, MD, MS

  University of Michigan, Obstetrics and Gynecology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 30, 2008
• First Posted: May 2, 2008
• Study Start: January 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: May 21, 2014
• Results First Posted: May 15, 2014

Record last verified: 2014-05

Locations

US (1)