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Dose-Response of Gonadal Steroids and Bone Turnover in Men

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
Solvay Pharmaceuticals
AstraZeneca
AbbVie
Information provided by (Responsible Party):
Joel S. Finkelstein, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00114114
First received: June 13, 2005
Last updated: October 17, 2013
Last verified: October 2013

June 13, 2005
October 17, 2013
September 2004
September 2015   (final data collection date for primary outcome measure)
Bone turnover [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Bone turnover
Complete list of historical versions of study NCT00114114 on ClinicalTrials.gov Archive Site
  • Body composition [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Strength [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Symptoms [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Sexual function [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Body composition
  • Strength
  • Symptoms
  • Sexual function
Not Provided
Not Provided
 
Dose-Response of Gonadal Steroids and Bone Turnover in Men
Dose-Response of Gonadal Steroids and Bone Turnover in Men

The purpose of this study is to determine the levels of testosterone and/or estradiol at which changes in bone turnover, body composition, strength, sexual function etc. begin to occur. This information may help determine when to intervene with hormone replacement therapy in aging men.

There are 3 arms to this protocol, each with 5 or 6 groups.

In Arm 1, 240 men age 20-50 will receive goserelin acetate (Zoladex) plus Androgel (or placebo). (Note Arm 1 is closed to recruitment).

In Arm 2, 200 men age 20-50 will receive goserelin acetate (Zoladex) plus Androgel (or placebo) plus anastrazole (Arimidex). (Note Arm 2 is closed to recruitment).

In Arm 3, 240 men age 60 to 75 will receive goserelin acetate (Zoladex) plus Androgel (or placebo). (Arm 3 is recruiting).

For each arm, subjects will be screened on the MGH General Clinical Research Center (GCRC). After obtaining informed consent for the screening procedures, subjects will undergo a complete history and physical examination. If no exclusionary findings are noted during the history and physical examination, blood will be drawn to measure hemoglobin, routine chemistries (including serum calcium, liver function tests, and creatinine), and serum levels of PTH, 25-OH vitamin D, TSH, T, and PSA.

Subjects who are successfully screened will be randomly assigned by a computer to one of 5 groups. All subjects will receive a GnRH agonist goserelin acetate (Zoladex; AstraZeneca, Wilmington, DE) 3.6 mg sc every 4 weeks for 16 weeks. Subjects in Group 1 will receive goserelin acetate and placebo for Androgel. Subjects in Groups 2-5 will receive varying doses of Androgel. In Arms 1 and 3, a sixth group will receive double placebo (e.g. placebo Zoladex and placebo Androgel). Subjects will be blinded with respect to group assignment. Dietary calcium intake will be assessed by a research dietitian and adjustments made through diet or supplements so that calcium intake is between 1000 and 1200 mg/day.

Subjects will be seen on the GCRC at 4 week intervals for 16 weeks (0, 4, 8, 12, and 16 weeks). At each visit, compliance with Androgel' will be assessed by reviewing a medication diary. A standardized series of questions will be posed to each subject to assess potential side effects of the study drugs. Subjects receiving Androgel' will be given a new 4 week supply of medication (except at week 16). A fasting blood and second voided urine sample will be collected. After the blood and urine samples have been obtained, subjects will be given their goserelin injection. The blood and urine tests listed below as well as anthropometric measures, and questionnaires will be performed at each visit. DXA, CT scans, and strength assessments will be performed at 0 and 16 weeks only. Subjects who discontinue participation at or after week 8 will be asked if they are willing to have an early discontinuation visit in which all procedures normally done at week 16 will be performed.

The following measures will be assessed:

  • Routine chemistries and PSA (for safety assessment)
  • Bone turnover using blood and urine tests
  • Hormones
  • Lipids
  • Body composition
  • Strength
  • Symptoms of hypogonadism
  • Bone mineral density and bone microarchitecture
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
Healthy Volunteers
  • Drug: Testosterone
    Androgel placebo or 1.25, 2.5, 5. or 10 gms topically each day
    Other Name: Androgel
  • Drug: Testosterone
    Androgel placebo or 1.25, 2.5, 5. or 7.5 gms topically each day
    Other Name: Androgel
  • Drug: Anastrazole
    1 mg by mouth daily
    Other Name: Arimidex
  • Drug: Goserelin acetate
    3.6 gms sc every 4 weeks
    Other Name: Zoladex
  • Placebo Comparator: 1
    Zoladex plus testosterone (or placebo) in men age 20-50. This arm is complete and no longer recruiting.
    Interventions:
    • Drug: Testosterone
    • Drug: Goserelin acetate
  • Placebo Comparator: 2
    Zoladex plus testosterone (or placebo) plus anastrazole in men age 20-50. This arm is complete and no longer recruiting.
    Interventions:
    • Drug: Testosterone
    • Drug: Anastrazole
    • Drug: Goserelin acetate
  • Placebo Comparator: 3
    Zoladex plus testosterone (or placebo) in men age 60 to 75
    Interventions:
    • Drug: Testosterone
    • Drug: Goserelin acetate
Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, Leder BZ. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Sep 12;369(11):1011-22. doi: 10.1056/NEJMoa1206168.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
900
September 2015
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Healthy men age 20 to 50 years or 60 to 75

Exclusion Criteria:

  • History of significant cardiac, renal, pulmonary, hepatic, benign prostatic hyperplasia, or malignant disease, current alcohol or illicit drug abuse, or major psychiatric disorders.
  • Current diagnoses of disorders known to affect bone metabolism including hyperthyroidism, hyperparathyroidism, osteomalacia, or Paget's disease.
  • Current use of medications known to affect bone metabolism including estrogens, androgens, anti-estrogens, bisphosphonates, calcitonin, fluoride, oral or inhaled glucocorticoids, suppressive doses of thyroxine, lithium, pharmacological doses of vitamin D (greater than 2000 IU/day), or anti-convulsants.
  • Cognitive or intellectual impairment that precludes complete understanding of the study protocol.
  • History of deep vein thrombosis, pulmonary embolism, or clotting disorders.
  • Serum 25-OH vitamin D < 15 ng/mL
  • Serum PTH < 10 or > 65 pg/mL
  • Serum TSH < 0.5 or > 5.0 U/L
  • Serum calcium > 10.6 mg/dL
  • Serum creatinine > 2 mg/dL
  • Serum AST or ALT > 2x the upper limit of normal
  • Serum bilirubin > 2 mg/dL
  • Serum alkaline phosphatase > 150 U/L
  • Plasma hemoglobin < 11 gm/dL
  • Hematocrit > 50
  • Fracture within the last 6 months.
  • Serum testosterone level < 270 or > 1070 ng/dL
  • Serum PSA level > 4 ug/L.
  • International Prostate Symptom Score (IPSS) > 19
  • Systolic blood pressure > 160 or diastolic blood pressure > 95
  • Framingham risk score greater than or equal to 20
  • Difficulty walking 2 blocks
Male
60 Years to 75 Years
Yes
Contact: JOEL S. FINKELSTEIN, MD 617-726-6723 jfinkelstein@partners.org
United States
 
NCT00114114
2003-P-001868, R01AG030545
No
Joel S. Finkelstein, MD, Massachusetts General Hospital
Massachusetts General Hospital
  • National Institute on Aging (NIA)
  • Solvay Pharmaceuticals
  • AstraZeneca
  • AbbVie
Principal Investigator: JOEL S. FINKELSTEIN, MD Massachusetts General Hospital
Massachusetts General Hospital
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP