The Role of 5-Alpha Reductase in Mediating Testosterone Actions - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00493987

Purpose

In normal men, the male hormone testosterone affects a number of things in the body including muscle function and sexual function. An enzyme in the body called 5-alpha reductase converts testosterone into another form called dihydrotestosterone (DHT) which has slightly different effects. The purpose of this study is to find out how different amounts of the two different forms of testosterone affect muscle function and sexual function in healthy young men like you. This will be done by giving the men participating in the study different combinations of hormone-related medication for 20 weeks and making measurements before, during and after the medications to look for changes in lean body tissue, muscle size, muscle strength and leg power, as well as sexual function and sexual activity in all participants.

Condition	Intervention	Phase
Healthy	Drug: Testosterone Enanthate Drug: Dutasteride	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	The Role of 5-Alpha Reductase in Mediating Testosterone Actions

Resource links provided by NLM:

MedlinePlus related topics: Nuclear Scans

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Dutasteride Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Change from baseline in fat-free mass, measured by DEXA scanning [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Body composition by Deuterium dilution method [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Maximal voluntary strength in the leg press and chest press exercises. [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Upper and lower extremity muscle power [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Muscle volume by MRI scan [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Prostate volume by MRI Scan [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]
International Index of Erectile Function [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Men's Sexual Health Questionnaire [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Davidson Sexual Encounter Profile [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Nocturnal penile tumescence and penile rigidity measures [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Prostate specific antigen [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Hematocrit [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Fasting lipid profile / atherogenic markers [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	184
Study Start Date:	November 2002
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Testosterone enanthate: Active Comparator	Drug: Testosterone Enanthate testosterone ester
Duatesteride: Placebo Comparator Duatesteride	Drug: Dutasteride 5 alpha-reductase inhibitor

Detailed Description:

Testosterone, the predominant circulating androgen in men, also serves as a prohormone that is converted in the body to two active metabolites, estradiol 17 β and 5-α DHT (DHT). Testosterone serves as the active hormone in some target tissues; however, androgen effects in other target organs require its conversion to estradiol or DHT. The role of 5-α reduction of testosterone in mediating its effects on the muscle and sexual function remains unclear. Therefore, the primary objective of this project is to determine whether 5-α reduction of testosterone to DHT is obligatory for mediating its effects on fat-free mass, muscle size, muscle strength, and leg power in men. The secondary objective is to determine whether 5-α reduction of testosterone is necessary for maintenance of androgen effects on sexual function (sexual desire, overall sexual activity, nocturnal penile tumescence (NPT), response to visual erotic stimulus, and penile rigidity) in men. In order to test these hypotheses about the role of 5-α reduction, we will compare testosterone dose response curves for each outcome measure in the absence and presence of a novel, potent 5-α reductase inhibitor (dutasteride) that inhibits both type 1 and type 2 steroid 5-α -reductase isoenzymes. Healthy young men, 21-40 years of age, will be treated with a long acting GnRH agonist to suppress endogenous testosterone production, and concomitantly, randomly assigned to one of 8 groups: group 1, testosterone enanthate (TE) 50-mg weekly, plus placebo tablets daily; group 2, TE 125-mg weekly plus placebo daily; group 3, TE 300-mg weekly plus placebo daily; group 4, TE 600 mg TE weekly plus placebo; group 5, 50-mg weekly, plus dutasteride 2.5-mg daily; group 6, TE 125-mg weekly, plus dutasteride daily; group 7, TE 300 mg weekly, plus dutasteride daily; group 8, 600-mg TE plus dutasteride daily. Energy and protein intake, and exercise stimulus will be standardized. The following outcomes will be measured at baseline and after 20 weeks: body composition by DEXA scan, deuterium oxide and sodium bromide dilution; thigh muscle volume by MRI scan; muscle performance by measurements of 1-repetition maximum strength and leg power; sexual function by International Index of Erectile Function, Sexual Desire Inventory, and daily logs of sexual activity; and penile erections and rigidity during EEG-coupled, NPT recoding and in response to a visual erotic stimulus; total and free testosterone, DHT, estradiol, SHBG, and LH levels. For safety, we will follow hemoglobin/hematocrit, sleep apnea scores, AST and ALT, PSA, plasma lipids, apolipoproteins, and lipoprotein particles, and prostate examinations. A multi-disciplinary team of investigators, the use of a previously validated "Leydig Cell Clamp" model, the use of a potent inhibitor of both subtypes of 5-alpha reductase enzyme, attention to potential confounding variables such as energy intake and exercise stimulus, and power and effect size should help elucidate the role of 5-alpha reduction in mediating androgen action. This study will enhance our understanding of the biologic role of the steroid 5-alpha-reductase system, and has immediate clinical relevance in establishing whether selective androgen receptor modulators that do not undergo 5-alpha reduction would be useful as anabolic agents.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy males between 18 and 50 years of age.
Ambulatory, physically active, but not in competitive sports.
Eugonadal: Normal Serum Testosterone (300-1100 nmol/L).
Normal LH
Normal FSH
Able and willing to comply with the trial protocol.

Exclusion Criteria:

Known to have a primary or secondary hypogonadism? (e.g. pituitary disease, HIV infection, Klinefelter's Syndrome)
BMI > 35
Disability that precludes participation in exercise testing
Alcohol or illicit drug use in the preceding 6 months that would interfere with participation and compliance with the protocol
Known disorder that would be exacerbated by androgen treatment e.g. benign prostate hyperplasia, prostate Ca, erythrocytosis, sleep apnea)
Any abnormalities in the following laboratory tests PSA > 4 ng/ml AST, ALT or Alkaline Phosphatase > 3x ULN? Creatinine level > 2 mg/dL Hematocrit > 51%
Osteoporosis by DEXA BMD T-Score < -2.5
Use of medications that affect muscle or bone metabolism within the previous 3 months ?(e.g. glucocorticoids, growth hormone, androgenic steroids, oral androgen precursors -i.e. androstenedione or DHEA)
Use of medications that affect androgen metabolism, action or clearance within the previous 3 months? (e.g. dilantin, phenobarbital, aldactone, flutamide, finasteride and Ketoconazole)
Use of ketoconazole or other potent CYP3A4 inhibitors that may affect clearance of dutasteride
Use investigational medication as part of a research study in the last 3 months?

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493987

Contacts

Contact: Samson H Hanka, BSc	617-414-2935	samson.hanka@bmc.org
Contact: Nurahmed H Mohammed, MSc	617-414-2935	nurahmed.mohammed@bmc.org

Locations

United States, Massachusetts
Boston University Medical Center	Recruiting
Boston, Massachusetts, United States, 02118
Principal Investigator: Shalender Bhasin, MD
Sub-Investigator: Kishore M Lakshman, MD MPH
Sub-Investigator: Shehzad Basaria, MD

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:

Shalender Bhasin, MD

Boston University

More Information

No publications provided

Responsible Party:	Boston University Medical Center ( Dr. Shalender Bhasin )
Study ID Numbers:	R01HD043348, R01HD043348
Study First Received:	June 28, 2007
Last Updated:	February 26, 2009
ClinicalTrials.gov Identifier:	NCT00493987 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Testosterone
Androgens
Dihydrotestosterone
5-alpha reductase
Body Composition

Muscle
Sexual function
Men
Healthy Men

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Enzyme Inhibitors
Methyltestosterone
Hormones

Pharmacologic Actions
Testosterone 17 beta-cypionate
Dutasteride
Testosterone
Anabolic Agents
Therapeutic Uses
Androgens

ClinicalTrials.gov processed this record on February 09, 2010