Conditions: Prostate Cancer
Keywords: Prostate Cancer Metformin Castration therapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 41
Healthy volunteers: no

Brief summary:
Prostate cancer is the most common non-cutaneous cancer in men. Patients with recurrent or metastatic prostate cancer are treated with androgen-deprivation therapy, often termed castration therapy. While the short and medium term benefits of castration are clear in relation to therapeutic efficacy in patients with prostate cancer, it is now appreciated that the resulting hypogonadism associated with castration is responsible for adverse consequences or metabolic syndrome that include increase in body mass index (BMI) and fat mass, hyperinsulinemia and insulin resistance, hyperlipidemia, reduced lean body mass (LBM) and muscle strength, osteoporosis, sexual dysfunction, poor quality of life and higher cardiovascular mortality. Lower testosterone levels in men independently predict the development of metabolic syndrome. Low testosterone levels in men are associated with insulin resistance and diabetes. Metformin is commonly prescribed for the treatment of type II diabetes because it lowers both glucose and insulin levels. Studies show preliminary evidence that metformin might have both antineoplastic and chemopreventative activity. Castration therapy decreases insulin sensitivity, adversely alters lipid profiles and results in weight gain, and it may be associated with a greater incidence of diabetes and cardiovascular disease. Little is known about the optimal strategy to mitigate the adverse metabolic effects of castration in men with prostate cancer. The rationale for using metformin in castrated men with advanced prostate cancer stems from the observation that castration therapy is associated with the metabolic syndrome, hyperinsulinemia and insulin resistance. Furthermore, reports that hyperinsulinemia stimulates insulin receptor expression on prostate cancer leading to tumor growth and development of castrate resistant prostate cancer suggest metformin through its activation of the AMPK-LKBI pathway reduces liver gluconeogenesis secondarily decreasing insulin levels may circumvent tumor growth and resistance to castration therapy. More importantly, evidence that metformin inhibits the mTOR pathway implicates an added therapeutic benefit as an anti-cancer agent.

Detailed description:

Arms:
arm 1: Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. arm 2: Metabolic consequences including development of hyperinsulinemia and insulin resistance using metformin compared to placebo in men on castration therapy. In the rare case where a patient may not tolerate 500 mg three times a day, he may remain on the study taking only 500 mg twice a day.

Interventions: intervention 1: Placebo intervention 2: Metformin
Intervention descriptions: intervention 1: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of placebo after castration, blinded to the patient and the study team. intervention 2: All eligible subjects will be randomized in a 1:l manner to receive a bottle containing sufficient 500mg tablets of metformin after castration, blinded to the patient and the study team.

Protocol document: