Study of Brain Function in Women With Insulin Resistant Polycystic Ovary Syndrome - Full Text View

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: Open Label 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:

MedlinePlus related topics: Diabetes Medicines Polycystic Ovary Syndrome

Drug Information available for: Metformin Metformin hydrochloride Insulin human

U.S. FDA Resources

Further study details as provided by University of Michigan:

Primary Outcome Measures:

PCOS affected women will be evaluated prior to and following 4-month metformin treatment utilizing the following measures: OGTT, neuropsychological testing battery, fMRI and PET scanning results. [ Time Frame: Once ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Hormonal studies [ Time Frame: prior to and following 4-months metformin treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	January 2008
Estimated Study Completion Date:	December 2015
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: 1: Control Control subjects will have 5 visits (screening, OGTT, neuropsych, fMRI and 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: 2: PCOS Subjects with PCOS will be scheduled for 9 visits total: following the screening visit they will go through OGTT, neuropsychological testing, fMRI and PET scan before and after 4 months of metformin use.	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 BID adding a dose after lunch. On the third week, a 500 mg tablet will be added after supper for a final dose of 500 mg orally TID. 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

Arms

Assigned Interventions

No Intervention: 1: Control

Control subjects will have 5 visits (screening, OGTT, neuropsych, fMRI and 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: 2: PCOS

Subjects with PCOS will be scheduled for 9 visits total: following the screening visit they will go through OGTT, neuropsychological testing, fMRI and PET scan before and after 4 months of metformin use.

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 BID adding a dose after lunch. On the third week, a 500 mg tablet will be added after supper for a final dose of 500 mg orally TID. 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.

AIM I. Determine whether identifiable differences can be observed in cognitive and emotional processing between women with insulin resistant PCOS compared to normal controls using validated fMRI tasks.

AIM II. Determine whether treatment with oral hypoglycemic agent will alter cognitive processing as measured with validated fMRI cognitive and emotional tasks.

AIM III. Evaluate the differences in opioid tone in women with insulin resistant PCOS compared to normal controls.

AIM IV. 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:

Subjects with insulin resistant PCOS, irregular menstrual cycles and hyperandrogenism.
Normal controls with regular menstrual cycles
Normal hormonal levels, without hirsutism and acne are BMI matched and screened for insulin resistance prior to inclusion.

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

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:

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. Epub 2011 Apr 12.

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
Last Updated:	February 10, 2012
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 May 23, 2013