Effect of Testosterone in Men With Erectile Dysfunction (TED)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Boston University
ClinicalTrials.gov Identifier:
NCT00512707
First received: August 7, 2007
Last updated: March 6, 2012
Last verified: March 2012
  Purpose

The purpose of this placebo-controlled study is to determine if testosterone replacement therapy, administered by transdermal gel, can improve the response to sildenafil (Viagra R) treatment in men who have erectile dysfunction (ED) and low testosterone levels.


Condition Intervention Phase
Erectile Dysfunction
Testosterone Deficiency
Diabetes
Drug: Sildenafil citrate (open label)
Drug: Testosterone gel 1% (active or placebo)
Drug: Topical testosterone gel 1%
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Androgen Modulation of Response to Selective Phosphodiesterase Inhibitors in Erectile Dysfunction

Resource links provided by NLM:


Further study details as provided by Boston University:

Primary Outcome Measures:
  • The primary outcome measure is the change from baseline (measured on the optimal sildenafil dose) in Erectile Function domain score of the International Index of Erectile Function (IIEF). [ Time Frame: The testosterone treatment period last for a total of 16 weeks (the final 12 weeks corresponds to the adjusted dose in the active treatment group). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Other domains/ responses from the IIEF, Sexual function diaries, Men's Sexual Health Questionnaire, Quality of Life (QOL-MED), Global assessment question, RigiScan response to visual erotic stimulus, and mood assessed by the PGWB and DABS questionnaires [ Time Frame: The testosterone treatment period last for a total of 16 weeks (the final 12 weeks corresponds to the adjusted dose in the active treatment group). ] [ Designated as safety issue: No ]

Enrollment: 152
Study Start Date: November 2006
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Active Testosterone Gel
Drug: Sildenafil citrate (open label)
On demand use of sildenafil citrate (3 tablets per week). Starting dose of 50 mg. Titrated to 100 mg or 25 mg depending on efficacy and tolerability. Begins as open label run in period for 3 - 6 weeks, and continues during the placebo-controlled testosterone gel intervention for 16 weeks.
Other Name: Viagra (Pfizer Inc.)
Drug: Testosterone gel 1% (active or placebo)
Testosterone Gel 1%: Starting active dose 10 g/day. Increased to 15 g/day or decreased to 5 g/day in order to attain morning total testosterone level between 500 - 1000 ng/dL. Blinding achieved by combining a total of 3 tubes of active or placebo gel, applied to upper arms and shoulders each day.
Other Name: Testim (Auxilium Pharmaceuticals, Inc.)
Drug: Topical testosterone gel 1%
Testosterone Gel: Starting dose 10 g/day. Increased to 15 g/day or decreased to 5 g/day in order to attain morning total testosterone level between 500 - 1000 ng/dL. Blinded achieved by combining a total of 3 tubes of active or placebo gel.
Other Name: Testim 1% (Auxilium Pharmaceuticals, Inc.)
Placebo Comparator: 2
Placebo Gel
Drug: Sildenafil citrate (open label)
On demand use of sildenafil citrate (3 tablets per week). Starting dose of 50 mg. Titrated to 100 mg or 25 mg depending on efficacy and tolerability. Begins as open label run in period for 3 - 6 weeks, and continues during the placebo-controlled testosterone gel intervention for 16 weeks.
Other Name: Viagra (Pfizer Inc.)
Drug: Testosterone gel 1% (active or placebo)
Testosterone Gel 1%: Starting active dose 10 g/day. Increased to 15 g/day or decreased to 5 g/day in order to attain morning total testosterone level between 500 - 1000 ng/dL. Blinding achieved by combining a total of 3 tubes of active or placebo gel, applied to upper arms and shoulders each day.
Other Name: Testim (Auxilium Pharmaceuticals, Inc.)

Detailed Description:

This is a double-blind, placebo-controlled, parallel-group, randomized clinical trial in men, 40-70 years of age, who present with mild to moderate erectile dysfunction and have androgen deficiency defined as serum total testosterone level below 300 ng/dL, measured by liquid chromatography tandem mass spectrometry, LC-MS/MS (15) and/or free testosterone level (measured by equilibrium dialysis) below 50 pg/ml. Sexual function assessments will include validated erectile function questionnaires (IIEF), sexual activity diaries, sexual desire, partner interaction and intimacy, affects balance scale, mood, ED-related quality of life, and penile rigidity in response to a visual erotic stimulus. The initial assessment will be made prior to treatment with sildenafil citrate, i.e., in subjects who are naïve to or withdrawn from PDE5 inhibitors and/or testosterone. Participants will then be allotted three sildenafil citrate tablets per week (12 pills per month), but will not use more than one tablet within any 24-hour period. During the Sildenafil-Dose Optimization period, subjects naïve to sildenafil citrate will start with a 50 mg dose. Those who have used sildenafil citrate in the past will take the same dose that was found to be efficacious for them. After three weeks, the dose of sildenafil citrate will be increased to 100-mg in non-responders. For those who cannot tolerate the 50-mg dose, a dose of 25 mg will be given. After three weeks on the optimized dose of sildenafil citrate, subjects will undergo a second evaluation of sexual function. They will then be randomly assigned to receive this optimized dose of sildenafil citrate with either placebo gel (15 g per day) or active testosterone gel (10 g active gel + 5 g placebo gel per day). The daily dose of active testosterone gel was selected to increase average serum into the upper-half of the normal range for healthy, young men (e.g., 500-1000 ng/dL). In order to assure that serum testosterone levels are in the target range (500-1000 ng/dL), testosterone dose will be adjusted by an unblinded individual two to three weeks after initiation of testosterone/placebo treatment, based on the measurement of serum testosterone levels. If the average testosterone level is less than 500 ng/dL, the daily dose will be increased to 15g of active gel. If the average testosterone is greater than 1,000 ng/dL, the daily dose will be decreased to 5 g of active gel (and 10 g of placebo gel). This dose adjustment will take effect at week 4 (day 28) of treatment. Subjects will be treated for an additional 12-weeks with sildenafil citrate and the optimized dose of testosterone gel or placebo gel. Sexual function will be evaluated at the end of this treatment period.

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men, 40-70 years of age, in a stable relationship, with mild to moderate erectile dysfunction for at least 6 months; defined as an IIEF-EF domain score between 11 and 25 (mild to moderate ED)
  • Neutral or extremely dissatisfied with one's sex life
  • Presence of androgen deficiency defined as serum total testosterone level less than 300 ng/dL (measured by LC-MS/MS) and/or free testosterone level (measured by equilibrium dialysis) less than 50 pg/ml.
  • Able to understand the nature of the study and provide written, informed consent

Exclusion Criteria:

  • Contraindication for use of testosterone, e.g., history of prostate or breast cancer
  • benign prostatic hyperplasia with AUA/IPSS symptom scores of 21 or greater
  • erythrocytosis (hematocrit >50% at baseline)
  • untreated, severe sleep apnea
  • serum PSA levels >4 ug/L will be excluded unless they have had a urologic evaluation in the past three months to exclude prostate cancer.
  • Contraindication for use of sildenafil, e.g., symptomatic coronary artery disease taking long-acting or short-acting nitrate drugs on a regular basis.
  • Symptomatic postural hypotension
  • Congestive heart failure with class III or IV symptoms
  • History of myocardial infarction or stroke within the past six months
  • Primary diagnosis of another sexual disorder such as premature ejaculation
  • AST, ALT, alkaline phosphatase elevation greater than three times the upper limit of normal, creatinine greater than 2 mg/dL.
  • Currently taking testosterone or oral androgen precursors; unless willing to discontinue their use for 4 weeks (oral precursors or transdermal testosterone patch or gel) or 6 weeks (if injectable testosterone) before the initial screen visit.
  • Currently taking medications that affect androgen metabolism, action, or clearance (dilantin, phenobarbital, aldactone, flutamide, finasteride).
  • Uncontrolled diabetes mellitus or diabetes mellitus, e.g., if their baseline hemoglobin A1C is less than 8.5%.
  • Structural abnormalities of the penis, including Peyronie's disease, will be excluded.
  • Men who are taking medications for erectile dysfunction, including sildenafil, must stop using these medications for at least 4 weeks before starting Visit 2.
  • DSM-IV criteria for an Axis I psychiatric disorder within the past year, including depression; use of psychotropic medication for at least six months, or dementia is also an exclusion.
  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: NCT00512707

Locations
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston University
Investigators
Principal Investigator: Shalender Bhasin, MD Boston University
Study Director: Shehzad Basaria, MD Boston University
  More Information

No publications provided by Boston University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boston University
ClinicalTrials.gov Identifier: NCT00512707     History of Changes
Other Study ID Numbers: R01-HD047722-01A1
Study First Received: August 7, 2007
Last Updated: March 6, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Boston University:
testosterone
erectile dysfunction
sildenafil

Additional relevant MeSH terms:
Erectile Dysfunction
Sexual Dysfunction, Physiological
Genital Diseases, Male
Sexual Dysfunctions, Psychological
Sexual and Gender Disorders
Mental Disorders
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Phosphodiesterase Inhibitors
Sildenafil
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Cardiovascular Agents
Phosphodiesterase 5 Inhibitors
Urological Agents

ClinicalTrials.gov processed this record on August 28, 2014