TRADE-Testosterone Replacement and Dutasteride Effectiveness

Phase 4

Completed

Conditions: Hypogonadism
Benign Prostatic Hyperplasia

Interventions: Drug: Dutasteride
Drug: Testosterone gel
Drug: Placebo dutasteride

Registration Number: NCT00194675

Lead Sponsor: University of Washington

Brief Summary: The purpose of this research study is to determine whether the combination of the male hormone testosterone \[T\] in gel form and the oral drug dutasteride \[D\], 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).

Detailed Description: The primary aim of this study is to determine whether correction of hypogonadism using a combination of testosterone 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 53

Inclusion Criteria

Generally healthy older men 50 years old or older
Hypogonadism; low testosterone (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
Prostate Specific Antigen (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 Benign Prostatic Hyperplasia (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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Testosterone gel + oral dutasteride	Testosterone gel	Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily
Testosterone gel + oral placebo	Testosterone gel	Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily
Testosterone gel + oral placebo	Placebo dutasteride	Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily
Testosterone gel + oral dutasteride	Dutasteride	Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily

Primary Outcome Measures

Name	Time	Method
Effects of Testosterone Gel Alone or in Combination With Oral Dutasteride on Prostate Volume in Hypogonadal Men With Benign Prostatic Hyperplasia.	Baseline, Month 6

Secondary Outcome Measures

Name	Time	Method
The Effects of T Alone or in Combination With Dutasteride on Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men With Benign Prostatic Hyperplasia. (International Prostate Symptom Score)	Baseline, Month 3, Month 6	International Prostate Symptom Score to assess lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Minimum score = 0, maximum score = 35; mildly symptomatic score = 0-7; moderately symptomatic score = 8-19; severely symptomatic score = 20-35; no subscales.
Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA)	Baseline, Month 6
Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men (Uroflow)	Baseline, 3-months, 6-months
Signs and Symptoms Benign Prostatic Hyperplasia (BPH): Post-voiding Residual (PVR) Urinary Volume	Baseline, 3-months, 6-months
Serum Hormone Levels: Total Testosterone, Free Testosterone, and Dihydrotestosterone(DHT), Dehydroepiandrosterone(DHEA), and Androstenedione.	Baseline, 3-months, 6-months