TRADE-Testosterone Replacement and Dutasteride Effectiveness

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT00194675
• Collaborator: GlaxoSmithKline (Industry), Seattle Institute for Biomedical and Clinical Research (Other), VA Office of Research and Development (U.S. Fed), Solvay Pharmaceuticals (Industry)
• Enrollment: 53
• Location: 1
• Arms: 2
• Duration (Months): 69
• Patients Per Site Per Month: 0.8

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism; Benign Prostatic Hyperplasia	Drug: Dutasteride; Drug: Testosterone gel; Drug: Placebo dutasteride	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Testosterone Replacement and Dutasteride Effectiveness (TRADE)
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Testosterone gel + oral placebo Testosterone 1% gel 7.5 topical daily + placebo dutasteride orally daily	Drug: Testosterone gel; Testosterone gel 7.5 g daily topical; Other Names: Testim ; Drug: Placebo dutasteride; placebo dutasteride orally daily
Active Comparator: Testosterone gel + oral dutasteride Testosterone 1% gel 7.5 topical daily + dutasteride 0.5 mg orally daily	Drug: Dutasteride; Dutasteride 0.5 mg orally daily; Other Names: AndroGel ; Drug: Testosterone gel; Testosterone gel 7.5 g daily topical; Other Names: Testim

Outcome Measures

Primary Outcome Measures

1. Effects of Testosterone Gel Alone or in Combination With Oral Dutasteride on Prostate Volume in Hypogonadal Men With Benign Prostatic Hyperplasia. [Baseline, Month 6]

Secondary Outcome Measures

1. Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA) [Baseline, Month 6]

2. 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) [Baseline, Month 3, Month 6]

   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.

3. Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men (Uroflow) [Baseline, 3-months, 6-months]

4. Signs and Symptoms Benign Prostatic Hyperplasia (BPH): Post-voiding Residual (PVR) Urinary Volume [Baseline, 3-months, 6-months]

5. Serum Hormone Levels: Total Testosterone, Free Testosterone, and Dihydrotestosterone(DHT), Dehydroepiandrosterone(DHEA), and Androstenedione. [Baseline, 3-months, 6-months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Locations

	Site	City	State	Country	Postal Code
1	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
• VA Office of Research and Development
• Solvay Pharmaceuticals

Investigators

• Principal Investigator: Alvin M Matsumoto, MD, VA Puget Sound Health Care System

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Washington

Publications

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

• Responsible Party: Alvin M. Matsumoto, MD, Professor, University of Washington
• ClinicalTrials.gov Identifier: NCT00194675
• Other Study ID Numbers: 01166; 01166, 4-2280-V
• First Posted: Sep 19, 2005
• Last Update Posted: Dec 5, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Alvin M. Matsumoto, MD, Professor, University of Washington: androgen deficiency; testosterone; Benign Prostatic Hyperplasia; hypogonadism; prostate; BPH
• Additional relevant MeSH terms: Prostatic Hyperplasia; Hypogonadism; Hyperplasia; Testosterone; Dutasteride

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the VA Puget Sound Health Care System, Seattle, WA. 102 men were screened and 53 were randomized.
Pre-assignment Detail	49 were excluded. 4 withdrew consent, 3 lost to follow-up, 42 for inclusion/exclusion criteria: 3 could not tolerate MRI, 3 were previously on testosterone therapy, 21 had prostate volume <30cc, 12 had repeat serum testosterone >280 ng/mL, and 3 had prostate cancer or prostate intraepithelial neoplasia at pre-treatment prostate biopsy.

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months	Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months
Period Title: Overall Study
STARTED	27	26
COMPLETED	22	24
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride	Total
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months	Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months	Total of all reporting groups
Overall Participants	27	26	53
Age, Customized (participants) [Median (Standard Deviation) ]
Between 50 and 82 years	63.5 (8.0) 235.2%	63.6 (5.5) 244.6%	63.55 (6.8) 119.9%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	27 100%	26 100%	53 100%
Region of Enrollment (participants) [Number]
United States	27 100%	26 100%	53 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months	Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months
Measure Participants	27	26
Baseline, Day 0	54.2 (38.1)	44.4 (19.8)
Month 6	58.3 (38.7)	38.6 (18.4)

2. Secondary Outcome

Title	Serum and Intraprostatic Hormone Levels: Prostate Specific Antigen (PSA)
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months	Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months
Measure Participants	27	26
Baseline PSA	2.8 (2.9)	2.1 (1.3)
Month 6 PSA	3.1 (2.9)	1.4 (1.2)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months	Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months
Measure Participants	27	26
Baseline IPSS	13.5 (2.7)	13.3 (3.1)
Month 3- IPSS	11.6 (5.0)	10.2 (5.4)
Month 6 IPSS	11.1 (5.2)	10.3 (6.6)

4. Secondary Outcome

Title	Signs and Symptoms of Benign Prostatic Hyperplasia (BPH) in Hypogonadal Men (Uroflow)
Time Frame	Baseline, 3-months, 6-months

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% gel 7.5 daily + oral placebo dutasteride daily	Testosterone 1% gel 7.5 daily + dutasteride 0.5 mg po daily
Measure Participants	27	26
Baseline Uroflow, Baseline	13.8 (3.0)	13.4 (3.5)
Uroflow after 3 months of treatment	12.7 (3.4)	13.2 (5.8)
Uroflow after 6 months of treatment	13.8 (5.1)	14.6 (6.7)

5. Secondary Outcome

Title	Signs and Symptoms Benign Prostatic Hyperplasia (BPH): Post-voiding Residual (PVR) Urinary Volume
Time Frame	Baseline, 3-months, 6-months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% gel 7.5 daily + oral placebo dutasteride daily	Testosterone 1% gel 7.5 daily + dutasteride 0.5 mg po daily
Measure Participants	27	26
Baseline Post Residual Volume (PVR)	43 (44)	48 (55)
3 month Post Residual Volume	36 (36)	41 (42)
6 month Post Residual Volume	39 (45)	32 (36)

6. Secondary Outcome

Title	Serum Hormone Levels: Total Testosterone, Free Testosterone, and Dihydrotestosterone(DHT), Dehydroepiandrosterone(DHEA), and Androstenedione.
Time Frame	Baseline, 3-months, 6-months

Outcome Measure Data

Analysis Population Description

per protocol

Arm/Group Title	Testosterone Gel + Oral Placebo	Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months	Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months
Measure Participants	27	26
Total testosterone, baseline	206 (109)	213 (68)
Total testosterone, month 3	494 (331)	525 (268)
Total testosterone, month 6	481 (329)	534 (360)
Free testosterone, baseline	4.2 (2.0)	4.5 (1.8)
Free testosterone, month 3	11.3 (6.8)	12.0 (6.1)
Free testosterone, month 6	11.4 (11.1)	12.3 (9.6)
Dihydrotestosterone (DHT), baseline	47 (94)	28 (15)
Dihydrotestosterone (DHT), month 3	145 (120)	16 (11)
Dihydrotestosterone (DHT), month 6	134 (87)	12 (7)
Dehydroepiandrosterone (DHEA), baseline	72 (42)	99 (68)
Dehydroepiandrosterone (DHEA), month 3	98 (92)	109 (93)
Dehydroepiandrosterone (DHEA), month 6	97 (86)	111 (90)
Androstenedione, baseline	45 (21)	47 (28)
Androstenedione, month 3	99 (72)	140 (60)
Androstenedione, month 6	100 (57)	123 (61)

Adverse Events

Time Frame	4 years. The study was conducted from March 2005 - March 2009.
Arm/Group Title	Testosterone Gel + Oral Placebo		Testosterone Gel + Oral Dutasteride
Arm/Group Description	Testosterone 1% topical gel 7.5g daily + placebo dutasteride pill orally daily for 6 months		Testosterone 1% topical gel 7.5g daily + dutasteride 0.5 mg orally daily for 6 months
All Cause Mortality
	Testosterone Gel + Oral Placebo		Testosterone Gel + Oral Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Testosterone Gel + Oral Placebo		Testosterone Gel + Oral Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/27 (7.4%)		0/26 (0%)
Cardiac disorders
death from myocardial infarction	1/27 (3.7%)	1	0/26 (0%)	0
non-ST segment myocardial infarction	1/27 (3.7%)	1	0/26 (0%)	0
Other (Not Including Serious) Adverse Events
	Testosterone Gel + Oral Placebo		Testosterone Gel + Oral Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/27 (25.9%)		4/26 (15.4%)
Blood and lymphatic system disorders
Elevated hematocrit	2/27 (7.4%)	2	0/26 (0%)	0
Gastrointestinal disorders
exacerbation of pre-existing colitis	0/27 (0%)	0	1/26 (3.8%)	1
Reproductive system and breast disorders
mild breast tenderness	2/27 (7.4%)	2	2/26 (7.7%)	2
increase in prostate specific antigen (PSA)	2/27 (7.4%)	2	0/26 (0%)	0
Skin and subcutaneous tissue disorders
ezcema	0/27 (0%)	0	1/26 (3.8%)	1
rash	1/27 (3.7%)	1	0/26 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.