Exenatide and Metformin Therapy in Overweight Women With PCOS

July 10, 2007 updated by: Metabolic Center of Louisiana Research Foundation

Comparison of the Effects of Monotherapy With Exenatide or Metformin to Combined Exenatide and Metformin Therapy on Menstrual Cyclicity in Overweight Women With Polycystic Ovary Syndrome

Current research has shown that the use of diabetes management practices aimed at reducing insulin resistance and hyperinsulinemia (such as weight reduction and the administration of oral antidiabetic drugs) in women with PCOS can not only improve glucose and lipid metabolism but can also reverse testosterone abnormalities and restore menstrual cycles. A new medicine called exenatide (Byetta) has been found to reduce body weight, as well as, improve abnormal glucose metabolism in diabetics. This randomized study will compare Exenatide (Byetta) to extended release metformin (Fortamet) to combination therapy (both Byetta and Fortamet) on menstrual cyclicity, hormone profiles and metabolic profiles over a 24-week period in women with PCOS.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objectives: The objective of the present proposal is to compare the clinical, endocrine and metabolic effects of therapy with exenatide and metformin alone, to combination therapy in women with PCOS. This study will serve as a pilot investigation to open perspectives for future investigations combining insulin-sensitizing drugs with different mechanisms of action in patients with PCOS, especially ones for whom standard treatment with metformin is less effective.

Subjects : 60 oligomenorrheic overweight/obese (BMI >27) women meeting criteria for PCOS (age 18-40)· six or fewer menses /year or amenorrheic· clinical or laboratory evidence of hyperandrogenism (hirsutism or elevated testosterone (T))· PCOS ovary on ultrasound(need to meet criteria 1 and either 2 or 3 [or both]) Inclusion/Exclusion Criteria: Major EXCLUSION CRITERIA - FEMALE1) other uncorrected endocrinopathy- hyperprolactinemia, hyper- or hypothyroidism, congenital adrenal hyperplasia2) presence of overt diabetes or impaired glucose tolerance3) alterations in hepatic or renal function4) use of hormonal medications, insulin sensitizers or medications that interfere with carbohydrate metabolism for at least 8 weeks5) Any medical condition which, in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug6) Simultaneous participation in another clinical trial7) Known active substance abuse including tobacco and alcohol. (> 10 cigarettes/day)8) Refusal or inability to comply with protocol9) patient desiring pregnancy, pregnant, or breastfeeding Study Design: Balanced randomized parallel group clinical study with 3 treatment arms: metformin (1000 mg BID); exenatide (10 mcg BID) or combined (metformin 1000 mg BID; exenatide 10 mcg BID) therapy for 24 weeks.

Efficacy Measures: Primary- Menstrual Cyclicity ( # menses/ 24 weeks)Secondary-BMI, WHR, FAI (T/SHBG), DHEAS, lipids, insulin resistance-(HOMA and composite insulin sensitivity index [ SIOGTT), and pancreatic ß-cell function (corrected insulin response [CIRgp] and insulinogenic index [IGI] ).

Safety: For safety, all subjects who enter the study are evaluable. Subjects will be monitored for safety by assessment of adverse events, physical exams, vital signs and laboratory values.

Statistical methods/analysis: The measurement of menstrual frequency involves nominal data ( patients with/without regular cycles pre vs post-treatment and will be analyzed using the McNemar test (complex chi square for paired data). For all other analyses, in which the data are interval, parameters, such as androgens, lipids, insulin sensitivity, etc. will be evaluated using a SS/Treatment x Trials (pre/post) analyses of variance (ANOVA). This repeated measures design will allow us to determine if each of the treatment drugs had an effect and if they are significantly different from each other while controlling for individual patient differences Study Drug Regimens: Exenatide5 ug bid - 4 weeks10 ug bid - 20 weeks (end of study)Metformin500 mg qd 2 weeks500 mg bid 2 weeks 500 mg am, 1000 mg pm- 2 weeks1000 mg bid -18 weeks (end study) Exenatide plus MetforminExenatide- 5 ug bid-4 weeksMetformin 500 qd for 2 weeks, 500 mg bid 2 weeksExenatide- 10 ug -20 weeks (to end of study)Metformin-500 mg am, 1000 mg pm- 2 weeks - 1000 bid for 18 weeks (end of study)** Metformin may be adjusted at the discretion of the physician to a level that is tolerable in patients who cannot tolerate the full dose of metformin in combination with exenatide (combination therapy only )

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808
        • Facility: Metabolic Center of Louisiana Research Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:Overweight/obese women (BMI>27)

  1. Must have six or fewer menses /year or be amenorrheic
  2. Have either clinical or laboratory evidence of hyperandrogenism (hirsutism or elevated testosterone (T)) and /or PCOS ovary on ultrasound

Exclusion Criteria:

other uncorrected endocrinopathy- hyperprolactinemia, hyper- or hypothyroidism, congenital adrenal hyperplasia or presence of overt diabetes alterations in hepatic or renal function use of hormonal medications, insulin sensitizers or medications that interfere with carbohydrate metabolism for at least 8 weeks Known active substance abuse including tobacco and alcohol. Pregnancy, breastfeeding or desire for pregnancy during study interval (6 months

-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
- Menstrual Cyclicity ( # menses/ 24 weeks)
Time Frame: every 4 weeks
every 4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
BMI, WHR, FAI (T/SHBG), DHEAS, lipids,abdominal girth,
Time Frame: BMI,WHR,abdominal girth at start,12 weeks and 24 weeks, FAI, DHEAS, lipids at start and at 24 weeks
BMI,WHR,abdominal girth at start,12 weeks and 24 weeks, FAI, DHEAS, lipids at start and at 24 weeks
insulin resistance-(HOMA and composite insulin sensitivity index [ SIOGTT),
Time Frame: at start and at 24 weeks
at start and at 24 weeks
and pancreatic ß-cell function (corrected insulin response [CIRgp] and
Time Frame: at start and at 24 weeks
at start and at 24 weeks
insulinogenic index [IGI] ).
Time Frame: at start and at 24 weeks
at start and at 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Metabolic Center of Louisiana Research Foundation

Collaborators

Amylin Pharmaceuticals, LLC.

Investigators

  • Principal Investigator: Karen E Elkind-Hirsch, Ph.D., Woman's Health Research Institute
  • Principal Investigator: Rajat Bhushan, M.D., Metabolic Center of Louisiana Resarch Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

June 23, 2006

First Submitted That Met QC Criteria

June 23, 2006

First Posted (Estimate)

June 27, 2006

Study Record Updates

Last Update Posted (Estimate)

July 11, 2007

Last Update Submitted That Met QC Criteria

July 10, 2007

Last Verified

July 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RP06-010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Polycystic Ovary Syndrome

Clinical Trials on metformin, exenatide or combined (metformin & exenatide )

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bulgaria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe