Metformin in Preventing Androgen Deprivation Therapy Induced Insulin Resistance and Metabolic Syndrome (MVENT)

The main purpose of this study is to assess the efficacy of metformin in abrogating androgen deprivation therapy (ADT) induced insulin resistance as measured by homeostasis model assessment (HOMAIR) in men with non-metastatic prostate cancer.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Hypercholesterolemia
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2145
      • Westmead Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• ≥ 18 years of age
• ECOG ≤ 1
• Histologically confirmed prostate cancer of early or locally advanced stage, or metastatic prostate cancer with bone involvement only (≤ 5 sites of bone metastases only)
• Plan to receive ≥ 6 months continuous androgen deprivation therapy by a GnRH agonist
• Patients who are to receive antiandrogens with GnRH agonists are not excluded from the study. But the form, dose and duration of antiandrogen treatment should be recorded.
• Adequate renal function (Creatinine ≤ 177mMol/L and GFR >30 mls/min )
• Adequate hepatic function (Bilirubin must be ≤ 1.5 x upper limit of normal range, ALT and ALP must be ≤ 2.5 x upper limit of normal)

Exclusion Criteria:

• Visceral involvement
• > 5 sites of bone metastases
• History of confirmed diabetes mellitus (patients with impaired fasting glucose or impaired glucose intolerance will not be excluded) 12
• Treatment with medications that may alter glucose or insulin level within 3 months (including insulin, oral hypoglycemic agents, systemic corticosteroid of any dosage, atypical antipsychotic drugs of any dose)
• Malignant disease other than prostate cancer at the time of enrolment
• Bilateral orchiectomy
• Previous androgen deprivation therapy by a GnRH agonist or anti-androgen within last 12 months(patient who had a GnRH agonist more than 12 months ago are allowed if their testosterone levels are in the normal range at the time of recruitment)
• Chemotherapy within 6 months
• History of lactic acidosis
• Cardiac or respiratory insufficiency, severe infection that is likely to increase the risk of lactic acidosis
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin	Drug: Metformin; Metformin 1500mg nocte for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage change in insulin resistance measured by homeostasis model assessment (HOMAIR) from baseline to 12 and 24 weeks	12 and 24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the efficacy of metformin in abrogating ADT-induced insulin resistance as measured by whole-body insulin sensitivity index(ISI) at 3 and 6 months	12 and 24 weeks
To assess the efficacy of metformin in reducing the incidence of ADT-induced metabolic syndrome at 3 and 6 months	12 and 24 weeks
To assess the efficacy of metformin in reducing ADT-induced percentage body fat mass gain 6 months	24 weeks
To assess the efficacy of metformin in reducing ADT-induced hypercholesterolemia at 3 and 6 months	12 and 24 weeks
To validate measurement of insulin resistance by HOMAIR with euglycemic hyperinsulinemic clamp in a subgroup group of participants	24 weeks

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District
• Investigators: Principal Investigator: Howard Gurney, MBBS, FRACP, Westmead Cancer Care Centre

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: February 26, 2010
• First Submitted That Met QC Criteria: February 26, 2010
• First Posted (Estimate): March 1, 2010

Study Record Updates

• Last Update Posted (Estimate): May 15, 2014
• Last Update Submitted That Met QC Criteria: May 13, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Insulin resistance; body fat mass gain
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Hyperinsulinism; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Syndrome; Metabolic Syndrome; Insulin Resistance; Hypercholesterolemia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: HGWH009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No