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TRADE-Testosterone Replacement and Dutasteride Effectiveness

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Seattle Institute for Biomedical and Clinical Research
Solvay Pharmaceuticals
Information provided by (Responsible Party):
Alvin M. Matsumoto, MD, University of Washington
ClinicalTrials.gov Identifier:
NCT00194675
First received: September 13, 2005
Last updated: July 16, 2012
Last verified: July 2012
  Purpose

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).


Condition Intervention Phase
Hypogonadism
Benign Prostatic Hyperplasia
Drug: Dutasteride
Drug: Testosterone gel
Drug: Placebo dutasteride
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Testosterone Replacement and Dutasteride Effectiveness (TRADE)

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Effects of Testosterone Gel Alone or in Combination With Oral Dutasteride on Prostate Volume in Hypogonadal Men With Benign Prostatic Hyperplasia. [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA) [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: Yes ]
  • Androgen-responsive Gene Expression and Proliferation in the Stromal and Epithelial Compartments of the Prostate [ Time Frame: 6-months ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Baseline, Month 3, Month 6 ] [ Designated as safety issue: No ]
    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.

  • Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men (Uroflow) [ Time Frame: Baseline, 3-months, 6-months ] [ Designated as safety issue: No ]
  • Signs and Symptoms Benign Prostatic Hyperplasia (BPH): Post-voiding Residual (PVR) Urinary Volume [ Time Frame: Baseline, 3-months, 6-months ] [ Designated as safety issue: No ]
  • Serum Hormone Levels: Total Testosterone, Free Testosterone, and Dihydrotestosterone(DHT), Dehydroepiandrosterone(DHEA), and Androstenedione. [ Time Frame: Baseline, 3-months, 6-months ] [ Designated as safety issue: Yes ]

Enrollment: 53
Study Start Date: March 2005
Study Completion Date: December 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Testosterone + oral placebo
Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily
Drug: Testosterone gel
Testosterone gel 7.5 g daily topical
Other Name: Testim
Drug: Placebo dutasteride
placebo dutasteride orally daily
Active Comparator: Testosterone + oral dutasteride
Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily
Drug: Dutasteride
Dutasteride 0.5 mg orally daily
Other Name: AndroGel
Drug: Testosterone gel
Testosterone gel 7.5 g daily topical
Other Name: Testim

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00194675

Locations
United States, Washington
VA Puget Sound Health Care System
Seattle, Washington, United States, 98108
Sponsors and Collaborators
University of Washington
GlaxoSmithKline
Seattle Institute for Biomedical and Clinical Research
Solvay Pharmaceuticals
Investigators
Principal Investigator: Alvin M Matsumoto, MD VA Puget Sound Health Care System
  More Information

Additional Information:
Publications:

Responsible Party: Alvin M. Matsumoto, MD, Professor, University of Washington
ClinicalTrials.gov Identifier: NCT00194675     History of Changes
Other Study ID Numbers: 01166, 01166, 4-2280-V
Study First Received: September 13, 2005
Results First Received: May 2, 2012
Last Updated: July 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
androgen deficiency
testosterone
Benign Prostatic Hyperplasia
hypogonadism
prostate
BPH

Additional relevant MeSH terms:
Hyperplasia
Hypogonadism
Prostatic Hyperplasia
Endocrine System Diseases
Genital Diseases, Male
Gonadal Disorders
Pathologic Processes
Prostatic Diseases
Dutasteride
Methyltestosterone
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
5-alpha Reductase Inhibitors
Anabolic Agents
Androgens
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Urological Agents

ClinicalTrials.gov processed this record on November 19, 2014