Testosterone and Growth Hormone for Bone Loss in Men

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Peter Snyder, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00080483
First received: April 5, 2004
Last updated: June 12, 2014
Last verified: December 2013
  Purpose

Deficiency of testosterone, growth hormone, or both hormones can result in osteoporosis. If either hormone is replaced, the condition of the bones improves. The purpose of this study is to determine if dual hormone treatment for men deficient in testosterone and growth hormone improves bone structure more than testosterone treatment alone.


Condition Intervention Phase
Hypopituitarism
Hypogonadism
Growth Hormone Deficiency
Drug: Testosterone plus somatropin
Drug: testosterone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Will Testosterone and Growth Hormone Improve Bone Structure?

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. [ Time Frame: baseline, one year, two years ] [ Designated as safety issue: No ]
    Increased bone volume fraction (the fraction of bone that is bone, as opposed to the fraction that is marrow), as determined by magnetic resonance of the distal tibia


Other Outcome Measures:
  • Increased Trabecular Thickness, as Determined by Magnetic Resonance of the Distal Tibia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Improved Architectural Parameters of Trabecular Bone Reflecting Connectivity, as Determined by Magnetic Resonance Imaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Increased Cortical Thickness and Cortical Density, as Determined by Peripheral Quantitative Computed Tomography of the Tibial Metaphysis [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: March 2004
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Testosterone transdermally 5 g a day and somatropin subcutaneously 2 µg/kg body weight a day
Drug: Testosterone plus somatropin
AndoGel 5 grams transdermally a day for two years Somatropin 2 µg/kg body weight/day for two years
Active Comparator: 2
AndroGel transdermally 5 g a day for two years
Drug: testosterone
AndroGel transdermally 5 g a day for two years

Detailed Description:

Replacement of testosterone or growth hormone in patients who are deficient improves osteoporosis associated with these deficiencies. In some tissues, such as muscle, the effects of testosterone and growth hormone are additive, but it is not known if the effects are additive in bone as well. This study will compare the effects of testosterone alone with testosterone plus growth hormone in improving bone structure in men with total pituitary hormone deficiency.

Participants in this study will be men who have pituitary or hypothalamic disease and have deficiencies of all pituitary hormones, but who have not been treated with either testosterone or growth hormone. The men will be randomly assigned to receive either testosterone alone or testosterone plus growth hormone for two years. Testosterone in a gel form will be applied daily to the skin. Growth hormone will be self-administered by daily subcutaneous injection. Blood concentrations of both hormones will be monitored with blood tests every 3 months during the 2-year study. Doses of the hormones will be adjusted to keep blood concentrations of the hormones within the normal range. Changes in bone structure will be assessed noninvasively before treatment and after one year and two years of treatment by magnetic resonance microimaging (µMRI) and dual energy X-ray absorptiometry (DEXA).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented hypothalamic or pituitary hormone deficiency
  • Testosterone deficiency, defined as total serum testosterone less than 250 ng/dL at two 8 AM readings
  • Growth hormone deficiency, defined by either of the following:
  • For subjects who have thyroxine and cortisol deficiencies, either a subnormal age-specific IGF-1 or a peak GH response to arginine-GHRH of less than 4.1 ng/mL
  • For subjects who do not have thyroxine and cortisol deficiencies, either a subnormal age-specific IGF-1 or a peak GH response to arginine-GHRH of less than 4.1 ng/mL
  • Duration of testosterone and growth hormone deficiencies of two years or more
  • Replacement of cortisol and/or thyroxine deficiencies
  • Able to give informed consent

Exclusion Criteria:

  • Current testosterone treatment or treatment during the two years prior to study entry
  • Current growth hormone treatment or treatment during the three years prior to study entry
  • Use of other prescription or over-the-counter androgens (androstenedione, DHEA), estrogens, or antiandrogens (spironolactone, ketoconazole)
  • Diseases that could influence bone, such as hyperparathyroidism
  • Medications that could influence bone, such as anticonvulsants or glucocorticoids (prednisone greater than 20 mg/day for longer than 2 weeks/year). Calcium and over-the-counter vitamin D supplements are allowed.
  • Cancer that could limit life expectancy to fewer than 5 years
  • Neuromuscular disease or history of stroke with residual neurological defect
  • Severe or uncontrolled psychiatric illness or dementia
  • Noncancerous enlargement of the prostate gland (American Urological Association symptom score greater than 21)
  • Prostate cancer by history, prostate nodule on digital rectal exam (DRE), or prostate specific antigen (PSA) greater than 4
  • Current alcohol or drug dependence
  • Heart failure (New York class III or IV)
  • Unstable angina
  • Myocardial infarction within 3 months of study entry
  • Liver disease (ALT greater than 3 x normal)
  • Renal disease (serum creatinine greater than 2.5 mg/dl)
  • Diabetes mellitus (glycosolated hemoglobin greater than 8.0%)
  • Hypertension (systolic BP greater than 160 or diastolic BP greater than 100 mm Hg)
  • Hematocrit greater than 48%
  • Weight greater than 300 pounds
  • Poor quality scan at baseline even when repeated
  • Untreated, severe, obstructive sleep apnea (Epworth sleepiness score greater than 10)
  • Unable to undergo an MRI because of a cardiac pacemaker or ferrometallic objects in the body
  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: NCT00080483

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Peter J. Snyder, MD University of Pennsylvania
Principal Investigator: Cecilia Lansang, MD University of Florida
  More Information

Publications:
Responsible Party: Peter Snyder, Professor of Medicine, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00080483     History of Changes
Other Study ID Numbers: R01 AR050618, R01AR050618, NIAMS-118
Study First Received: April 5, 2004
Results First Received: December 12, 2013
Last Updated: June 12, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Hypopituitarism
Dwarfism, Pituitary
Hypogonadism
Endocrine System Diseases
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Gonadal Disorders
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Hormones
Androgens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on August 01, 2014