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Castration Compared to Castration Plus Metformin as First Line Treatment for Patients With Advanced Prostate Cancer

NCT01620593 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 41

Last updated 2018-05-23

Study results available
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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.

Conditions

Interventions

DRUG

Placebo

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.

DRUG

Metformin

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.

Sponsors & Collaborators

  • The University of Texas Health Science Center at San Antonio

    lead OTHER

Principal Investigators

  • Devalingam Mahalingam, MD, PhD · University of Texas Health Science Center San Antonio

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
MALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2011-04-30
Primary Completion
2016-07-31
Completion
2016-09-30

Countries

  • United States

Study Locations

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Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01620593 on ClinicalTrials.gov