TRADE-Testosterone Replacement and Dutasteride Effectiveness

NCT ID: NCT00194675

Last Updated: 2017-12-05

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2010-12-31

Brief Summary

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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

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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.

Conditions

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Hypogonadism Benign Prostatic Hyperplasia

Keywords

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androgen deficiency testosterone Benign Prostatic Hyperplasia hypogonadism prostate BPH

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Testosterone gel + oral placebo

Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily

Group Type ACTIVE_COMPARATOR

Testosterone gel

Intervention Type DRUG

Testosterone gel 7.5 g daily topical

Placebo dutasteride

Intervention Type DRUG

placebo dutasteride orally daily

Testosterone gel + oral dutasteride

Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily

Group Type ACTIVE_COMPARATOR

Dutasteride

Intervention Type DRUG

Dutasteride 0.5 mg orally daily

Testosterone gel

Intervention Type DRUG

Testosterone gel 7.5 g daily topical

Interventions

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Dutasteride

Dutasteride 0.5 mg orally daily

Intervention Type DRUG

Testosterone gel

Testosterone gel 7.5 g daily topical

Intervention Type DRUG

Placebo dutasteride

placebo dutasteride orally daily

Intervention Type DRUG

Other Intervention Names

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AndroGel Testim

Eligibility Criteria

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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.
Minimum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Seattle Institute for Biomedical and Clinical Research

OTHER

Sponsor Role collaborator

VA Office of Research and Development

FED

Sponsor Role collaborator

Solvay Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Alvin M. Matsumoto, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alvin M Matsumoto, MD

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System

Locations

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VA Puget Sound Health Care System

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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. doi: 10.1034/j.1601-5215.2002.51018.x.

Reference Type BACKGROUND
PMID: 12534854 (View on PubMed)

Yialamas MA, Hayes FJ. Androgens and the ageing male and female. Best Pract Res Clin Endocrinol Metab. 2003 Jun;17(2):223-36. doi: 10.1016/s1521-690x(03)00018-6.

Reference Type BACKGROUND
PMID: 12787549 (View on PubMed)

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. doi: 10.1046/j.1365-2265.2001.01240.x.

Reference Type BACKGROUND
PMID: 11318778 (View on PubMed)

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. doi: 10.1111/j.1365-2265.1994.tb03929.x.

Reference Type BACKGROUND
PMID: 7514512 (View on PubMed)

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. doi: 10.3322/canjclin.22.4.232. No abstract available.

Reference Type BACKGROUND
PMID: 4625049 (View on PubMed)

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. doi: 10.1002/j.1939-4640.2003.tb02676.x. No abstract available.

Reference Type BACKGROUND
PMID: 12721204 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8968017 (View on PubMed)

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. doi: 10.1002/pros.1046.

Reference Type BACKGROUND
PMID: 11304729 (View on PubMed)

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. doi: 10.1056/NEJMoa030660. Epub 2003 Jun 24.

Reference Type BACKGROUND
PMID: 12824459 (View on PubMed)

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. doi: 10.1210/jcem.86.4.7413.

Reference Type BACKGROUND
PMID: 11297606 (View on PubMed)

Page ST, Hirano L, Gilchriest J, Dighe M, Amory JK, Marck BT, Matsumoto AM. Dutasteride reduces prostate size and prostate specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy. J Urol. 2011 Jul;186(1):191-7. doi: 10.1016/j.juro.2011.03.026. Epub 2011 May 14.

Reference Type RESULT
PMID: 21575967 (View on PubMed)

Other Identifiers

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01166, 4-2280-V

Identifier Type: OTHER

Identifier Source: secondary_id

01166

Identifier Type: -

Identifier Source: org_study_id