Clinical trial NCT01077479: Metformin in Preventing Androgen Deprivation Therapy Induced Insulin Resistance and Metabolic Syndrome
Official title: Metformin in Preventing Androgen Deprivation Therapy Induced Insulin Resistance and Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metabolic Syndrome
Hypercholesterolemia
Keywords: body fat mass gain
Insulin resistance
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
First posted: 2010-03-01
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: The percentage change in insulin resistance measured by homeostasis model assessment (HOMAIR) from baseline to 12 and 24 weeks
timeFrame: 12 and 24 weeks
Secondary outcomes:
measure: 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
timeFrame: 12 and 24 weeks
measure: To assess the efficacy of metformin in reducing the incidence of ADT-induced metabolic syndrome at 3 and 6 months
timeFrame: 12 and 24 weeks
measure: To assess the efficacy of metformin in reducing ADT-induced percentage body fat mass gain 6 months
timeFrame: 24 weeks
measure: To assess the efficacy of metformin in reducing ADT-induced hypercholesterolemia at 3 and 6 months
timeFrame: 12 and 24 weeks
measure: To validate measurement of insulin resistance by HOMAIR with euglycemic hyperinsulinemic clamp in a subgroup group of participants
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
affiliation: Westmead Cancer Care Centre
name: Howard Gurney, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
References: