TRADE-Testosterone Replacement and Dutasteride Effectiveness

Study Overview
=================
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.

Official Title
-----------------
Testosterone Replacement and Dutasteride Effectiveness (TRADE)

Conditions
-----------------
Hypogonadism, Benign Prostatic Hyperplasia

Intervention / Treatment
-----------------
* Drug: Dutasteride
* Drug: Testosterone gel
* Drug: Placebo dutasteride


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Testosterone gel + oral placebo<br>Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily | Drug: Testosterone gel<br>* Testosterone gel 7.5 g daily topical<br>* Other names: Testim;Drug: Placebo dutasteride<br>* placebo dutasteride orally daily<br>|
| Active Comparator: Testosterone gel + oral dutasteride<br>Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily | Drug: Dutasteride<br>* Dutasteride 0.5 mg orally daily<br>* Other names: AndroGel;Drug: Testosterone gel<br>* Testosterone gel 7.5 g daily topical<br>* Other names: Testim;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA) |  | Baseline, Month 6 | 
| 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) | 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. | Baseline, Month 3, 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
androgen deficiency, testosterone, Benign Prostatic Hyperplasia, hypogonadism, prostate, BPH