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

Polycystic Ovary Syndrome Clinical Trial

Official title:

Influence of Insulin Resistance on Cognitive, Emotional and Opioid System Functioning in Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00670800
• Other study ID #: 2276
• Secondary ID: HUM00008330
• Status: Completed
• Phase: N/A
• First received: April 30, 2008
• Last updated: May 15, 2014
• Start date: January 2008
• Est. completion date: August 2009

Study information

• Verified date: May 2014
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years to 40 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance
• Polycystic Ovary Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan, Michigan Clinical Research Unit	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. do — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No