Exenatide and Metformin Therapy in Overweight Women With PCOS

Polycystic Ovary Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00344851
• Other study ID #: RP06-010
• Status: Completed
• Phase: Phase 2
• First received: June 23, 2006
• Last updated: July 10, 2007
• Start date: June 2006
• Est. completion date: June 2007

Study information

• Verified date: July 2007
• Source: Metabolic Center of Louisiana Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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 )

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome

Intervention

Drug:
• metformin, exenatide or combined (metformin & exenatide )

Locations

Country	Name	City	State
United States	Facility: Metabolic Center of Louisiana Research Foundation	Baton Rouge	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Metabolic Center of Louisiana Research Foundation	Amylin Pharmaceuticals, LLC.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- Menstrual Cyclicity ( # menses/ 24 weeks)		every 4 weeks
Secondary	BMI, WHR, FAI (T/SHBG), DHEAS, lipids,abdominal girth,		BMI,WHR,abdominal girth at start,12 weeks and 24 weeks, FAI, DHEAS, lipids at start and at 24 weeks
Secondary	insulin resistance-(HOMA and composite insulin sensitivity index [ SIOGTT),		at start and at 24 weeks
Secondary	and pancreatic ß-cell function (corrected insulin response [CIRgp] and		at start and at 24 weeks
Secondary	insulinogenic index [IGI] ).		at start and at 24 weeks