TRADE-Testosterone Replacement and Dutasteride Effectiveness - Full Text View

Sponsor:	University of Washington
Collaborators:	GlaxoSmithKline Seattle Institute for Biomedical and Clinical Research Department of Veterans Affairs Solvay Pharmaceuticals
Information provided by:	University of Washington
ClinicalTrials.gov Identifier:	NCT00194675

Purpose

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).

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Placebo Control 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:

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Dutasteride Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

The effects of T alone or in combination with dutasteride on prostate volume in hypogonadal men with BPH. [ Time Frame: 6-months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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

Estimated Enrollment:	75
Study Start Date:	June 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Testosterone 1% gel 7.5 daily + placebo dutasteride po daily	Drug: Testosterone gel Testosterone gel 7.5 g daily Drug: Placebo dutasteride placebo dutasteride po daily
2: Active Comparator Testosterone 1% gel 7.5 daily + dutasteride 0.5 mg po daily	Drug: Dutasteride Dutasteride 0.5 mg daily Drug: Testosterone gel Testosterone gel 7.5 g daily

Detailed Description:

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.

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 (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.

Contacts and Locations

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

Contacts

Contact: Janet Gilchriest, RN	206-768-5408	janet.gilchriest@med.va.gov
Contact: Kathy Winter	206-768-5370

Locations

United States, Washington
VA Puget Sound Health Care System	Recruiting
Seattle, Washington, United States, 98108
Contact: Kathy Winter 206-616-0484
Contact: Janet Gilchriest, RN 206-768-5408
Sub-Investigator: Stephanie T Page, MD, PhD
Sub-Investigator: Peter Nelson, MD
Sub-Investigator: Daniel Lin, MD
Sub-Investigator: John K Amory, MD
Sub-Investigator: Paul R Sutton, MD, PhD
Sub-Investigator: Bradley D Anawalt, MD
Sub-Investigator: William J Bremner, MD, PhD
Sub-Investigator: David Hess, PhD

Sponsors and Collaborators

University of Washington

GlaxoSmithKline

Seattle Institute for Biomedical and Clinical Research

Department of Veterans Affairs

Solvay Pharmaceuticals

Investigators

Principal Investigator:

Alvin M Matsumoto, MD

Puget Sound Veterans Administration Health Care System

More Information

Additional Information:

University of Washington This link exits the ClinicalTrials.gov site

Publications:

Gruenewald DA, Matsumoto AM. Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc. 2003 Jan;51(1):101-15; discussion 115. Review.

Yialamas MA, Hayes FJ. Androgens and the ageing male and female. Best Pract Res Clin Endocrinol Metab. 2003 Jun;17(2):223-36. Review.

Jin B, Conway AJ, Handelsman DJ. Effects of androgen deficiency and replacement on prostate zonal volumes. Clin Endocrinol (Oxf). 2001 Apr;54(4):437-45.

Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf). 1994 Mar;40(3):341-9.

Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972 Jul-Aug;22(4):232-40. No abstract available.

Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J Androl. 2003 May-Jun;24(3):299-311. Review. No abstract available.

Morgentaler A, Bruning CO 3rd, DeWolf WC. Occult prostate cancer in men with low serum testosterone levels. JAMA. 1996 Dec 18;276(23):1904-6.

Schatzl G, Madersbacher S, Thurridl T, Waldmuller J, Kramer G, Haitel A, Marberger M. High-grade prostate cancer is associated with low serum testosterone levels. Prostate. 2001 Apr;47(1):52-8.

Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul 17;349(3):215-24. Epub 2003 Jun 24.

Monti S, Di Silverio F, Iraci R, Martini C, Lanzara S, Falasca P, Poggi M, Stigliano A, Sciarra F, Toscano V. Regional variations of insulin-like growth factor I (IGF-I), IGF-II, and receptor type I in benign prostatic hyperplasia tissue and their correlation with intraprostatic androgens. J Clin Endocrinol Metab. 2001 Apr;86(4):1700-6.

Responsible Party:	VA Puget Sound Health Care System ( Alvin M Matsumoto, MD )
Study ID Numbers:	01166, 04-2280-V, 26264-V
Study First Received:	September 13, 2005
Last Updated:	September 23, 2009
ClinicalTrials.gov Identifier:	NCT00194675 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Washington:

androgen deficiency
testosterone
BPH
hypogonadism
prostate

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Prostatic Diseases
Antineoplastic Agents
Gonadal Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Endocrine System Diseases
Enzyme Inhibitors
Methyltestosterone
Genital Diseases, Male
Hormones

Pharmacologic Actions
Testosterone 17 beta-cypionate
Dutasteride
Anabolic Agents
Hyperplasia
Testosterone
Hypogonadism
Pathologic Processes
Prostatic Hyperplasia
Therapeutic Uses
Androgens

ClinicalTrials.gov processed this record on March 18, 2010