Dose-Response of Gonadal Steroids and Bone Turnover in Men

This study is currently recruiting participants.
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
  Purpose

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.


Condition Intervention
Healthy Volunteers
Drug: Testosterone
Drug: Anastrazole
Drug: Goserelin acetate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Diagnostic
Official Title: Dose-Response of Gonadal Steroids and Bone Turnover in Men

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Bone turnover [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 900
Study Start Date: September 2004
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Zoladex plus testosterone (or placebo) in men age 20-50. This arm is complete and no longer recruiting.
Drug: Testosterone
Androgel placebo or 1.25, 2.5, 5. or 10 gms topically each day
Other Name: Androgel
Drug: Goserelin acetate
3.6 gms sc every 4 weeks
Other Name: Zoladex
Placebo Comparator: 2
Zoladex plus testosterone (or placebo) plus anastrazole in men age 20-50. This arm is complete and no longer recruiting.
Drug: Testosterone
Androgel placebo or 1.25, 2.5, 5. or 10 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: 3
Zoladex plus testosterone (or placebo) in men age 60 to 75
Drug: Testosterone
Androgel placebo or 1.25, 2.5, 5. or 7.5 gms topically each day
Other Name: Androgel
Drug: Goserelin acetate
3.6 gms sc every 4 weeks
Other Name: Zoladex

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   60 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00114114

Contacts
Contact: JOEL S. FINKELSTEIN, MD 617-726-6723 jfinkelstein@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: JOEL S. FINKELSTEIN, MD    617-726-6723    jfinkelstein@partners.org   
Contact: Benjamin Z Leder, MD    617-726-6723    bzleder@partners.org   
Principal Investigator: JOEL S. FINKELSTEIN, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Solvay Pharmaceuticals
AstraZeneca
AbbVie
Investigators
Principal Investigator: JOEL S. FINKELSTEIN, MD Massachusetts General Hospital
  More Information

No publications provided by Massachusetts General Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Joel S. Finkelstein, MD, Associate Professor ofMedicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00114114     History of Changes
Other Study ID Numbers: 2003-P-001868, R01AG030545
Study First Received: June 13, 2005
Last Updated: October 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Testosterone
Bone turnover
Aging
Body composition
Hypogonadism
Sexual function

Additional relevant MeSH terms:
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Goserelin
Anastrozole
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014