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

June 20, 2011 updated by: University of Washington

The Effect of Dihydrotestosterone (DHT) on Prostate Tissue Androgen Concentrations and Inflammation in Normal Men

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 17β-Hydroxy-5α-androstane-3-one
Placebo Comparator: 2
Placebo gel for one month
Drug: Placebo gel
Placebo gel for one month

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate Tissue DHT and Testosterone Levels After 28 Days of Treatment With Dihydrotestosterone [DHT] Gel Versus Placebo Gel.
Time Frame: 28-days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate Epithelial Cell Proliferation
Time Frame: 28-days
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.
28-days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Institute on Aging (NIA)
ASCEND Therapeutics

Investigators

  • Principal Investigator: Stephanie T Page, MD, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

June 20, 2007

First Submitted That Met QC Criteria

June 21, 2007

First Posted (Estimate)

June 22, 2007

Study Record Updates

Last Update Posted (Estimate)

June 27, 2011

Last Update Submitted That Met QC Criteria

June 20, 2011

Last Verified

June 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 31866-A
  • 1K23AG027238-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Healthy

Clinical Trials on Dihydrotestosterone (DHT) gel (0.7%)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe