Growth Hormone Deficiency, Hypogonadism, Hypopituitarism
Conditions
Brief summary
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.
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).
Interventions
DRUGTestosterone plus somatropin
AndoGel 5 grams transdermally a day for two years Somatropin 2 µg/kg body weight/day for two years
DRUGtestosterone
AndroGel transdermally 5 g a day for two years
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | baseline, one year, two years | 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
| Measure | Time frame |
|---|---|
| Increased Trabecular Thickness, as Determined by Magnetic Resonance of the Distal Tibia | 2 years |
| Improved Architectural Parameters of Trabecular Bone Reflecting Connectivity, as Determined by Magnetic Resonance Imaging | 2 years |
| Increased Cortical Thickness and Cortical Density, as Determined by Peripheral Quantitative Computed Tomography of the Tibial Metaphysis | 2 years |
Countries
United States
Participant flow
Recruitment details
This study was initiated in December, 2004 and enrollment ended in September 2008. Forty nine subjects were screened; 14 were screen failures and 35 subjects were randomized. Four subjects were withdrawn and 31 subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| 1Testosterone Only Testosterone transdermally 5 g a day | 17 |
| 2Testosterone Plus Growth Hormone AndroGel transdermally 5 g a day somatropin subcutaneously 2 µg/kg body weight a day | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | 1Testosterone Only | 2Testosterone Plus Growth Hormone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 17 Participants | 31 Participants |
| Region of Enrollment United States | 17 participants | 18 participants | 35 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 17 Participants | 18 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 17 | 11 / 18 |
| serious Total, serious adverse events | 4 / 17 | 4 / 18 |
Outcome results
Primary
MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment.
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
Time frame: baseline, one year, two years
Population: All subjects who had both baseline and one year evaluations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 The Effects of Testosterone Combined With G | MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | baseline | 0.112 unitless | Standard Error 0.004 |
| 1 The Effects of Testosterone Combined With G | MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | one year | 0.119 unitless | Standard Error 0.004 |
| 1 The Effects of Testosterone Combined With G | MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | two years | 0.123 unitless | Standard Error 0.005 |
| 2 The Effects of Testosterone Alone on Structural and Mechanic | MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | baseline | 0.104 unitless | Standard Error 0.004 |
| 2 The Effects of Testosterone Alone on Structural and Mechanic | MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | one year | 0.111 unitless | Standard Error 0.006 |
| 2 The Effects of Testosterone Alone on Structural and Mechanic | MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment. | two years | 0.114 unitless | Standard Error 0.005 |
Other Pre-specified
Improved Architectural Parameters of Trabecular Bone Reflecting Connectivity, as Determined by Magnetic Resonance Imaging
Time frame: 2 years
Other Pre-specified
Increased Cortical Thickness and Cortical Density, as Determined by Peripheral Quantitative Computed Tomography of the Tibial Metaphysis
Time frame: 2 years
Other Pre-specified
Increased Trabecular Thickness, as Determined by Magnetic Resonance of the Distal Tibia
Time frame: 2 years