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TRADE-Testosterone Replacement and Dutasteride Effectiveness (TRADE)

Primary Purpose

Hypogonadism, Benign Prostatic Hyperplasia

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Dutasteride
Testosterone gel
Placebo dutasteride
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogonadism focused on measuring androgen deficiency, testosterone, Benign Prostatic Hyperplasia, hypogonadism, prostate, BPH

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

  • VA Puget Sound Health Care System

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Testosterone gel + oral placebo

Testosterone gel + oral dutasteride

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 13, 2005
Last Updated
October 30, 2017
Sponsor
University of Washington
Collaborators
GlaxoSmithKline, Seattle Institute for Biomedical and Clinical Research, VA Office of Research and Development, Solvay Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00194675
Brief Title
TRADE-Testosterone Replacement and Dutasteride Effectiveness
Acronym
TRADE
Official Title
Testosterone Replacement and Dutasteride Effectiveness (TRADE)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
GlaxoSmithKline, Seattle Institute for Biomedical and Clinical Research, VA Office of Research and Development, Solvay Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism, Benign Prostatic Hyperplasia
Keywords
androgen deficiency, testosterone, Benign Prostatic Hyperplasia, hypogonadism, prostate, BPH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Testosterone gel + oral placebo
Arm Type
Active Comparator
Arm Description
Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily
Arm Title
Testosterone gel + oral dutasteride
Arm Type
Active Comparator
Arm Description
Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily
Intervention Type
Drug
Intervention Name(s)
Dutasteride
Other Intervention Name(s)
AndroGel
Intervention Description
Dutasteride 0.5 mg orally daily
Intervention Type
Drug
Intervention Name(s)
Testosterone gel
Other Intervention Name(s)
Testim
Intervention Description
Testosterone gel 7.5 g daily topical
Intervention Type
Drug
Intervention Name(s)
Placebo dutasteride
Intervention Description
placebo dutasteride orally daily
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA)
Time Frame
Baseline, Month 6
Title
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)
Description
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.
Time Frame
Baseline, Month 3, Month 6
Title
Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men (Uroflow)
Time Frame
Baseline, 3-months, 6-months
Title
Signs and Symptoms Benign Prostatic Hyperplasia (BPH): Post-voiding Residual (PVR) Urinary Volume
Time Frame
Baseline, 3-months, 6-months
Title
Serum Hormone Levels: Total Testosterone, Free Testosterone, and Dihydrotestosterone(DHT), Dehydroepiandrosterone(DHEA), and Androstenedione.
Time Frame
Baseline, 3-months, 6-months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alvin M Matsumoto, MD
Organizational Affiliation
VA Puget Sound Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12534854
Citation
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.
Results Reference
background
PubMed Identifier
12787549
Citation
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.
Results Reference
background
PubMed Identifier
11318778
Citation
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.
Results Reference
background
PubMed Identifier
7514512
Citation
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.
Results Reference
background
PubMed Identifier
4625049
Citation
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.
Results Reference
background
PubMed Identifier
12721204
Citation
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.
Results Reference
background
PubMed Identifier
8968017
Citation
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.
Results Reference
background
PubMed Identifier
11304729
Citation
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.
Results Reference
background
PubMed Identifier
12824459
Citation
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.
Results Reference
background
PubMed Identifier
11297606
Citation
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.
Results Reference
background
PubMed Identifier
21575967
Citation
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.
Results Reference
result
Links:
URL
http://depts.washington.edu/popctr/
Description
University of Washington

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TRADE-Testosterone Replacement and Dutasteride Effectiveness

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