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Dose-Response of Gonadal Steroids and Bone Turnover in Older Men

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ClinicalTrials.gov Identifier: NCT00114114
Recruitment Status : Completed
First Posted : June 14, 2005
Results First Posted : September 17, 2019
Last Update Posted : October 8, 2019
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Solvay Pharmaceuticals
AstraZeneca
AbbVie
Information provided by (Responsible Party):
Benjamin Leder, MD, Massachusetts General Hospital

Brief Summary:
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 in older men. This information may help determine when to intervene with hormone replacement therapy in aging men.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: Testosterone Drug: Goserelin acetate Not Applicable

Detailed Description:

In this protocol, men age 60-75 will be randomized to one of 6 groups. Groups 1-5 will receive goserelin acetate (Zoladex) plus 0 (placebo gel), 1.25, 2.5, 5, or 10* g/day of testosterone gel (Androgel). Group 6 will receive placebos for both goserelin acetate and testosterone gel. (*Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial due to reports of possible increased risk of cardiovascular events with testosterone administration).

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 Clinical Research Center 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. Dual-energy x-ray absorptiometry (DXA), quantitate computed tomography (QCT) 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 prostate specific antigen, PSA (for safety assessment)
  • Bone turnover using blood and urine tests
  • Hormones
  • Lipids
  • Body composition
  • Strength
  • Sexual desire and erectile function
  • Bone mineral density and bone microarchitecture

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 177 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Diagnostic
Official Title: Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
Study Start Date : September 2004
Actual Primary Completion Date : November 1, 2017
Actual Study Completion Date : November 1, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1: 0 g/day
Zoladex plus Placebo Testosterone (T) gel
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

Experimental: Group 2: 1.25 g/day
Zoladex plus 1.25 g/day T gel
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

Experimental: Group 3: 2.5 g/day
Zoladex plus 2.5 g/day T gel
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

Experimental: Group 4: 5 g/day
Zoladex plus 5 g/day T gel
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

Experimental: Group 5: 10* g/day
Zoladex plus 10* g/day T gel. *Note that the 10 g/day dose was reduced to 7.5 g/day part-way through the trial
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

Experimental: Group 6: Placebo/Placebo (PBO/PBO)
Placebo Zoladex plus Placebo T gel (controls)
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




Primary Outcome Measures :
  1. Percent Change in Bone Turnover Marker (Serum C-telopeptide, CTX) [ Time Frame: Baseline and 16 weeks ]

Secondary Outcome Measures :
  1. Percentage Change in Body Composition: Fat Mass [ Time Frame: Baseline and 16 weeks ]
  2. Percentage Change in Thigh Muscle Area [ Time Frame: Baseline and 16 weeks ]
    Assessed by quantitative computed tomography (QCT)

  3. Change in Erectile Function Symptoms [ Time Frame: Baseline and 16 weeks ]
    Based on International Index of Erectile Function (IIEF) scale, question #15, which asked subjects to rate their confidence that they could achieve and maintain an erection. Scores range from 1 to 5, with higher scores being better.

  4. Change in Libido / Sexual Desire [ Time Frame: 16 weeks ]
    Change in libido from baseline (scale ranges from -2 to +2), with -2 being much less, -1 somewhat less, 0 same, +1 somewhat more, +2 much more



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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy men age 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-hydroxyvitamin D < 15 ng/mL
  • Serum parathyroid hormone (PTH) < 10 or > 65 pg/mL
  • Serum thyroid stimulating hormone (TSH) < 0.5 or > 5.0 U/L
  • Serum calcium > 10.6 mg/dL
  • Serum creatinine > 2 mg/dL
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 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 prostate specific antigen (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00114114


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Institute on Aging (NIA)
Solvay Pharmaceuticals
AstraZeneca
AbbVie
Investigators
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Principal Investigator: Ben Z Leder, MD Massachusetts General Hospital
  Study Documents (Full-Text)

Documents provided by Benjamin Leder, MD, Massachusetts General Hospital:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Benjamin Leder, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00114114    
Other Study ID Numbers: 2003-P-001868
R01AG030545 ( U.S. NIH Grant/Contract )
First Posted: June 14, 2005    Key Record Dates
Results First Posted: September 17, 2019
Last Update Posted: October 8, 2019
Last Verified: September 2019
Keywords provided by Benjamin Leder, MD, Massachusetts General Hospital:
Testosterone
Bone turnover
Aging
Body composition
Hypogonadism
Sexual function
Additional relevant MeSH terms:
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Goserelin
Testosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents