TRADE-Testosterone Replacement and Dutasteride Effectiveness

Condition(s) targeted: Hypogonadism; Benign Prostatic Hyperplasia

Intervention: Dutasteride (Drug); Testosterone gel (Drug); Placebo dutasteride (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
Alvin M Matsumoto, MD, Principal Investigator, Affiliation: VA Puget Sound Health Care System

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).

Official title: Testosterone Replacement and Dutasteride Effectiveness (TRADE)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Effects of Testosterone Gel Alone or in Combination With Oral Dutasteride on Prostate Volume in Hypogonadal Men With Benign Prostatic Hyperplasia.

Secondary outcome:

Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA)

Androgen-responsive Gene Expression and Proliferation in the Stromal and Epithelial Compartments of the Prostate

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)

Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men (Uroflow)

Signs and Symptoms Benign Prostatic Hyperplasia (BPH): Post-voiding Residual (PVR) Urinary Volume

Serum Hormone Levels: Total Testosterone, Free Testosterone, and Dihydrotestosterone(DHT), Dehydroepiandrosterone(DHEA), and Androstenedione.

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.

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Male.

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.

VA Puget Sound Health Care System, Seattle, Washington 98108, United States

University of Washington

Related 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.

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.

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, Waldmüller 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.

Starting date: March 2005
Last updated: July 16, 2012