Official Title: “Testosterone Replacement and Dutasteride Effectiveness (TRADE)”

The purpose of this research study is to determine whether the combination of male hormone (testosterone [T]) and the drug dutasteride (that is used to shrink large prostate glands) can safely reduce the size of the prostate gland and symptoms of prostate enlargement (called benign prostatic hyperplasia [BPH]) compared to T treatment alone in men with low testosterone (called hypogonadism).

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

The primary aim of this study is to determine whether correction of hypogonadism using a combination of T and dutasteride spares subjects from increases in prostate size and symptoms of BPH which may be associated with T alone.

We will also determine the effects of changes in serum T and dihydrotestosterone (DHT) on both the hormonal milieu and genetic program within the prostate gland itself. The technology employed will allow us to determine which genes are androgen responsive within each prostate tissue compartment. Together, these data may determine whether the combination of testosterone and dutasteride safely corrects the symptoms of BPH and hypogonadism and minimizes growth stimulus to the prostate at the genetic level. We will also assess the effects of the combination of T and dutasteride on cognitive function.

This is a six-month, double-blind, randomized, placebo-controlled, single-site study of older hypogonadal men with mild to moderate BPH.

Within each treatment group, a sub-group of subjects will undergo additional procedures as part of a Prostate Biopsy sub-study to obtain prostate tissue for hormonal and genetic analyses. Selection of subjects will be based on clinical indication and/or willingness to undergo prostate biopsies. A sub-group of men who volunteer will have cognitive function testing performed before and at the end of treatment.

Intervention(s) in this Clinical Trial

• Drug: Dutasteride
  • Dutasteride 0.5 mg daily
• Drug: Testosterone gel
  • Testosterone gel 7.5 g daily
• Drug: Placebo dutasteride
  • placebo dutasteride po daily

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Testosterone 1% gel 7.5 daily + placebo dutasteride po daily
• Active Comparator: 2
  • Testosterone 1% gel 7.5 daily + dutasteride 0.5 mg po daily

Primary Measures

• The effects of T alone or in combination with dutasteride on prostate volume in hypogonadal men with BPH.
  • Time Frame: 6-months
    Safety Issue?: No

Secondary Measures

• The effects of T alone or in combination with dutasteride on:
  • Time Frame: 6-months
    Safety Issue?: No
• Symptoms and signs of BPH
  • Time Frame: 6-months
    Safety Issue?: Yes
• Serum and intraprostatic hormone levels
  • Time Frame: 6-months
    Safety Issue?: No
• Androgen-responsive gene expression and proliferation in the stromal and epithelial compartments of the prostate
  • Time Frame: 6-months
    Safety Issue?: No
• Spatial and verbal memory
  • Time Frame: 6-months
    Safety Issue?: No

Inclusion Criteria:

• Generally healthy older men 50 years old or older
• Hypogonadism (total T less than 280 ng/dL on one occasion or an average of equal to or less than 300 ng/dl on two occasions)
• Prostate volume equal to or more than 30 cc by prostate MRI
• PSA equal to or more than 1.5 ng/mL and equal to or less than 10 ng/mL
• Subjects with a PSA greater than 4.0 ng/ml must have a negative prostate biopsy
• International Prostate Symptom Score (IPSS) greater than or equal to 8 and less than or equal to 20 at screening
• Comply with study procedures for the full 10 months
• No contraindications to MRI
• Subjects with symptomatic BPH will be recruited from the Urology and General Internal
• Medicine Clinics at the VA Puget Sound Health Care System and University of Washington
• Medical Center in Seattle.

Exclusion Criteria:

• A history of prostate or breast cancer
• Invasive therapy for BPH in the past
• History of acute urinary retention in the 3 months prior to screening
• Previous treatment with a 5 alpha-reductase inhibitor (finasteride or dutasteride)
• Medical therapy for BPH within the past month (alpha-blocker, phytotherapy)
• Use of androgenic or antiandrogenic drugs in the past year
• History or evidence of prostate cancer including suspicious DRE or history of high-grade PIN on prostate biopsy.
• Severe systemic illness (renal, liver, cardiac, lung disease, cancer, diabetes)
• Known untreated obstructive sleep apnea
• Hematocrit greater than 52
• Severe skin disease which may interfere with testosterone gel absorption
• Hypersensitivity to any of the drugs used in the study
• History of a bleeding disorder or need for chronic anticoagulation
• Participation in a drug study concurrently or in the last 90 days
• History or current evidence of drug or alcohol abuse within 12 mo.
• Weight more than 300 lbs.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: University of Washington

Overall Clinical Trial Officials and Contacts

Alvin M Matsumoto, MD Principal Investigator VA Puget Sound Health Care System  

Overall Contact: Janet Gilchriest, RN 206-768-5408 janet.gilchriest@med.va.gov

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00194675

Study ID Number: 04-2280-V

ClinicalTrials.gov Identifier: NCT00194675

Health Authority: United States: Food and Drug Administration

University of Washington