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

This study has been completed.
Sponsor:
Collaborators:
ASCEND Therapeutics
Information provided by:
University of Washington
ClinicalTrials.gov Identifier:
NCT00490022
First received: June 20, 2007
Last updated: June 20, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Dihydrotestosterone (DHT) gel (0.7%)
Drug: Placebo gel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Dihydrotestosterone (DHT) on Prostate Tissue Androgen Concentrations and Inflammation in Normal Men

Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Prostate Tissue DHT and Testosterone Levels After 28 Days of Treatment With Dihydrotestosterone [DHT] Gel Versus Placebo Gel. [ Time Frame: 28-days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Prostate Epithelial Cell Proliferation [ Time Frame: 28-days ] [ Designated as safety issue: No ]
    Prostate epithelial cell proliferation in the prostate biopsy tissue was measured using Ki-67 immunohistochemical staining of prostate epithelium as a marker of cell proliferation (values are number of Ki-67 positive stained cells per 100 prostate epithelial cells). The placebo and treatment groups were compared.


Enrollment: 31
Study Start Date: June 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
DHT gel (70 mg/day) for one month
Drug: Dihydrotestosterone (DHT) gel (0.7%)
DHT gel, 70 mg/day for one month
Other Name: 17β-Hydroxy-5α-androstane-3-one
Placebo Comparator: 2
Placebo gel for one month
Drug: Placebo gel
Placebo gel for one month

Detailed Description:

In this study, we will examine the in vivo effects of DHT supplementation on the prostate and serum inflammatory markers at the molecular level. We hypothesize that increases in serum DHT will not increase intraprostatic DHT or prostate epithelial proliferation, and will be associated with decreases in markers of systemic inflammation. Normal, healthy, male study volunteers will be treated with either placebo gel (Group 1) or DHT gel (Group 2) for one month. Serum hormonal and inflammatory measurements will be assessed before, during, and after treatment, and the relationship between hormones and inflammatory markers associated with cardiovascular risk will be determined. Prostate biopsies will be taken after one month of treatment. Prostate tissue will be analyzed for changes in intraprostatic hormone levels as well as gene expression following treatment.

SPECIFIC AIMS:

  1. To determine the effect of increases in serum DHT, without concomitant increases in serum T or estrogen, on intraprostatic androgen levels.
  2. To determine the effect of increases in serum DHT, without concomitant increases in serum T or estrogen, on prostate epithelial gene expression.
  3. To determine the effect of increases in serum DHT, without concomitant increases in serum T or estrogen, on serum lipids and inflammatory markers including C-Reactive Protein [CRP], Tumor necrosis factor-alpha [TNFα], Interleukin-6 [IL-6], adiponectin, plasminogen activator inhibitor [PAI-I], and leptin.

We will test the hypothesis in normal men (rather than hypogonadal men) as a "proof of principle" investigation. A normal hypothalamic-pituitary-testicular axis and regulation, circulating T and DHT levels and intraprostatic androgen concentrations in healthy, normal men will permit optimal testing of the hypothesis. Exogenous DHT administration in normal men is expected to suppress endogenous gonadotropin and testosterone secretion, compared to more variable effects in hypogonadal men that depend on the degree of hypogonadism in these men and whether they have primary (testicular) or secondary (hypothalamic-pituitary) hypogonadism. Furthermore, intraprostatic T and DHT concentrations and 5 alpha-reductase activity (that is androgen-dependent) is expected to be more variable in hypogonadal men, depending on the degree of androgen deficiency and circulating T and DHT levels. If results in normal men support the hypothesis, subsequent studies could be performed in hypogonadal men. Because of the larger variability in circulating and probably intraprostatic androgen concentrations in hypogonadal men, these studies will require much larger numbers of subjects.

  Eligibility

Ages Eligible for Study:   35 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00490022

Locations
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
ASCEND Therapeutics
Investigators
Principal Investigator: Stephanie T Page, MD, PhD University of Washington
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stephanie T Page, MD, PhD, University of Washington
ClinicalTrials.gov Identifier: NCT00490022     History of Changes
Other Study ID Numbers: 31866-A, 1K23AG027238-01A1
Study First Received: June 20, 2007
Results First Received: January 10, 2011
Last Updated: June 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
Dihydrotestosterone
Androgen
Prostate

Additional relevant MeSH terms:
Dihydrotestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014