Dose-Response of Gonadal Steroids and Bone Turnover in Men - Full Text View

Sponsor:	Massachusetts General Hospital
Collaborators:	National Institute on Aging (NIA) Solvay Pharmaceuticals AstraZeneca
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00114114

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:

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Goserelin Anastrozole Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

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 2012
Estimated Primary Completion Date:	September 2012 (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

National Institute on Aging (NIA)

Solvay Pharmaceuticals

AstraZeneca

Investigators

Principal Investigator:

JOEL S. FINKELSTEIN, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Joel S. Finkelstein, M.D. Principal Investigator, 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:	July 20, 2011
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 February 09, 2012