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

NCT ID: NCT00670800

Last Updated: 2014-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2009-08-31

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.

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.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Glucophage

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Yolanda Smith, M.D.

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yolanda R Smith, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan, Obstetrics and Gynecology

Locations

University of Michigan, Michigan Clinical Research Unit

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21486668 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23557757 (View on PubMed)

Other Identifiers

HUM00008330

Identifier Type: OTHER

Identifier Source: secondary_id

2276

Identifier Type: -

Identifier Source: org_study_id