Effect of Dihydrotestosterone (DHT) on Prostate Tissue [Short Title: DHT-3]

NCT00490022 | Completed Phase 1 Results

• 2 other identifiers: 31866-A1K23AG027238-01A1
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to understand the effects of a male hormone normally made in the body called Dihydrotestosterone (DHT) on the prostate gland that is located under the bladder. The knowledge gained from this study may be used to help in the future to develop a safe male hormonal contraceptive to prevent pregnancy, in the safe treatment of low male hormone levels in men, and in the treatment and prevention of diseases of the prostate. The investigators will be giving DHT in a gel form, to be applied to the skin, or a placebo gel (with no active drug in it). The investigators want to see the effects of DHT on levels of hormones in the blood and in the prostate gland itself. In addition, the investigators will be studying the effects of DHT on the cells and genes expressed within the prostate. The effect of DHT on the prostate is not known. Some studies suggest blocking production of DHT in the prostate helps growth of the gland with aging (a condition known as benign prostatic hyperplasia, or BPH for short) and may prevent prostate cancer. On the other hand, DHT administration may shrink the prostate, suggesting it may be beneficial for some men. Therefore, further studies looking at the effect of DHT on the prostate are needed.

Conditions

Healthy

Keywords

Dihydrotestosterone; Androgen; Prostate

Outcome Measures

Primary Outcomes (1)

• Prostate Tissue DHT and Testosterone Levels After 28 Days of Treatment With Dihydrotestosterone [DHT] Gel Versus Placebo Gel.

  After 4 weeks of either daily dihydrotestosterone transdermal gel or placebo gel, subjects underwent a prostate biopsy. Intraprostatic hormone concentrations, specifically DHT and Testosterone, were measured. Unit of measure is ng/g.

  28-days

Secondary Outcomes (1)

• Prostate Epithelial Cell Proliferation

  28-days

Study Arms (2)

1

ACTIVE COMPARATOR

DHT gel (70 mg/day) for one month

Drug: Dihydrotestosterone (DHT) gel (0.7%)

2

PLACEBO COMPARATOR

Placebo gel for one month

Drug: Placebo gel

Interventions

Dihydrotestosterone (DHT) gel (0.7%) DRUG

DHT gel, 70 mg/day for one month

Also known as: 17β-Hydroxy-5α-androstane-3-one

1

Placebo gel DRUG

Placebo gel for one month

2

Eligibility Criteria

• Age: 35 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males 35-55 years old
• Normal serum total testosterone (300 ng/dl-1000 ng/dl)
• Normal Luteinizing Hormone \[LH\] and Follicle Stimulating Hormone \[FSH\] levels
• Informed consent
• Taking no regular medications
• Normal baseline prostate ultrasound, hematology, and liver function tests

You may not qualify if:

• History of prostate cancer
• Prostate Specific Antigen \[PSA\] \> 2.0
• American Urological Association \[AUA\] prostate symptom score \> 10
• History of testosterone or anabolic steroid use in the past
• Chronic medical illness or prostate disease
• History of a bleeding disorder or need for anticoagulation
• A first-degree relative (i.e. father, brother) with a history of prostate cancer
• Abnormal digital rectal examination
• Skin condition that might interfere with or be exacerbated by DHT gel use
• History of untreated sleep apnea and/or psychiatric problems
• Participation in another study in the past 2 months
• Participating in a regular physical relationship with a pregnant woman

Sponsors & Collaborators

• University of Washington: lead
• National Institute on Aging (NIA): collaborator
• ASCEND Therapeutics: collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (16)

• Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Jul;168(1):9-12. doi: 10.1016/s0022-5347(05)64820-3. No abstract available.

  PMID: 12050481 BACKGROUND

• 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.

  PMID: 12721204 BACKGROUND

• 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.

  PMID: 8968017 BACKGROUND

• 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.

  PMID: 11304729 BACKGROUND

• Wu FC, von Eckardstein A. Androgens and coronary artery disease. Endocr Rev. 2003 Apr;24(2):183-217. doi: 10.1210/er.2001-0025.

  PMID: 12700179 BACKGROUND

• Bagatell CJ, Heiman JR, Matsumoto AM, Rivier JE, Bremner WJ. Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. J Clin Endocrinol Metab. 1994 Aug;79(2):561-7. doi: 10.1210/jcem.79.2.8045977.

  PMID: 8045977 BACKGROUND

• Bartsch W, Klein H, Schiemann U, Bauer HW, Voigt KD. Enzymes of androgen formation and degradation in the human prostate. Ann N Y Acad Sci. 1990;595:53-66. doi: 10.1111/j.1749-6632.1990.tb34282.x. No abstract available.

  PMID: 1695829 BACKGROUND

• Bartsch W, Krieg M, Becker H, Mohrmann J, Voigt KD. Endogenous androgen levels in epithelium and stroma of human benign prostatic hyperplasia and normal prostate. Acta Endocrinol (Copenh). 1982 Aug;100(4):634-40. doi: 10.1530/acta.0.1000634.

  PMID: 6181638 BACKGROUND

• Page ST, Lin DW, Mostaghel EA, Hess DL, True LD, Amory JK, Nelson PS, Matsumoto AM, Bremner WJ. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab. 2006 Oct;91(10):3850-6. doi: 10.1210/jc.2006-0968. Epub 2006 Aug 1.

  PMID: 16882745 BACKGROUND

• Wilson JD. The role of 5alpha-reduction in steroid hormone physiology. Reprod Fertil Dev. 2001;13(7-8):673-8. doi: 10.1071/rd01074.

  PMID: 11999320 BACKGROUND

• Andriole GL, Humphrey P, Ray P, Gleave ME, Trachtenberg J, Thomas LN, Lazier CB, Rittmaster RS. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004 Sep;172(3):915-9. doi: 10.1097/01.ju.0000136430.37245.b9.

  PMID: 15310997 BACKGROUND

• Norman RW, Coakes KE, Wright AS, Rittmaster RS. Androgen metabolism in men receiving finasteride before prostatectomy. J Urol. 1993 Nov;150(5 Pt 2):1736-9. doi: 10.1016/s0022-5347(17)35882-2.

  PMID: 7692110 BACKGROUND

• Kunelius P, Lukkarinen O, Hannuksela ML, Itkonen O, Tapanainen JS. The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J Clin Endocrinol Metab. 2002 Apr;87(4):1467-72. doi: 10.1210/jcem.87.4.8138.

  PMID: 11932266 BACKGROUND

• Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ, Handelsman DJ. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab. 2001 Sep;86(9):4078-88. doi: 10.1210/jcem.86.9.7821.

  PMID: 11549629 BACKGROUND

• Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White J, Hood L, Lin B. The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11890-5. doi: 10.1073/pnas.182376299. Epub 2002 Aug 16.

  PMID: 12185249 BACKGROUND

• Page ST, Lin DW, Mostaghel EA, Marck BT, Wright JL, Wu J, Amory JK, Nelson PS, Matsumoto AM. Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial. J Clin Endocrinol Metab. 2011 Feb;96(2):430-7. doi: 10.1210/jc.2010-1865. Epub 2010 Dec 22.

  PMID: 21177791 DERIVED

MeSH Terms

Interventions

Dihydrotestosterone; Gels

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Stephanie Page, PhD, MD
• Organization: University of Washington

page@u.washington.edu

206.616.0483

Study Officials

• Stephanie T Page, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 22, 2007
• Study Start: June 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: June 27, 2011
• Results First Posted: June 9, 2011

Record last verified: 2011-06

Locations

US (1)