Official Title: “A Randomised Controlled Clinical Trial of Metformin Versus Orlistat for the Management of Obese Anovulatory Women.”

This study aims to investigate the role of the weight reduction agent, Orlistat compared to the Metformin for the management of women who are obese and do not ovulate or have difficulty conceiving. Patients will receive either one of these medications and will be monitored at regular intervals with hormone blood tests and ultrasound scans in order to study the effect of the medications on the reproductive functions. Patients will receive the medications for three months and the study will end if the patient becomes pregnant. The study also aims to investigate the dose of metformin that should be used as there is no consensus to date regarding the optimum dosage for this drug

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: February 2008

We aim to recruit 40 patients suffering from anovulatory obesity with a BMI of 30 or more. Patients will be included from all ethnic groups.

Patients will have a baseline history, clinical examination, hormonal profile (FSH/LH, fasting Insulin/glucose ratio, androgen profile, day 21 serum progesterone, serum leptin and ghrelin levels) ultrasound examination (ovarian volume and antral follicle count), including Doppler blood flow study (ovarian stromal velocity, PI, RI, SD ratio and power Doppler) Participants will then be randomised to receive either metformin or orlistat. Patients receiving orlistat will receive the standard dose of the drug as recommended in the BNF.

Metformin will be given in an incremental dose starting at 1000mg per day and increased at 4 weekly intervals to 2000mg/d, depending on the occurrence of any gastrointestinal intolerance. The endocrinological and ultrasound investigations will be repeated at 4 weekly intervals. Both groups will be given a standard exercise and diet program in conjunction with medical treatment.

The clinical endpoint will be the achievement of conception, a Body Mass Index of less than 30, or completion of a 3-month course of treatment.

Study design:

A randomised controlled open label clinical trial. Participants be randomised using a computer generated randomisation program available at the pharmacy of the Jessop Wing, into either one of two arms: metformin or orlistat. The randomisation will be stratified in order to achieve a homogenous distribution of PCOS and non-PCOS patients in both arms of the study.

Intervention(s) in this Clinical Trial

• Drug: Orlistat Vs Metformin

Primary Measures

• Outcome measures:
• 1- The occurrence of ovulation as measured by day-21 serum progesterone ( equal to or more than 30mmol/L).
• 2- Number of patients who have lost at least 5% of body weight at the end of the study.
• 3- Improvement/deterioration of clinical symptoms: hyper androgenic features, obesity and menstrual disturbances
• 4- Change in the ovarian Doppler indices.

Inclusion Criteria:

• 1. In the childbearing period 2. Obese with a body mass index of 30 or more. 3. Are anovulatory as shown by day 21-serum progesterone. 4. Polycystic ovarian syndrome will be diagnosed according if at least two of the following three features are present, after exclusion of other aetiologies (Azziz, 2004): (i) Oligo- or anovulation, (ii) Clinical and/or biochemical hyperandrogenism (iii) Polycystic ovaries.

Exclusion Criteria:

• 1. BMI of less than 30
• 2. Patients not requesting treatment for their symptoms
• 3. Patients with contraindications for any of the medications: renal or hepatic impairment, malabsorption syndrome, cholestasis
• 4. Diabetic patients
• 5. Pregnancy
• 6. Breast feeding

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 40 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Overall Clinical Trial Officials and Contacts

Professor William L Ledger, D.Phil,FRCOG Study Chair Sheffield University  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00292799

Study ID Number: STH14007

ClinicalTrials.gov Identifier: NCT00292799

Health Authority: United Kingdom: Research Ethics Committee