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Testosterone and Growth Hormone for Bone Loss in Men

Primary Purpose

Hypopituitarism, Hypogonadism, Growth Hormone Deficiency

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Testosterone plus somatropin
testosterone
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypopituitarism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Testosterone transdermally 5 g a day and somatropin subcutaneously 2 µg/kg body weight a day

AndroGel transdermally 5 g a day for two years

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
April 5, 2004
Last Updated
June 12, 2014
Sponsor
University of Pennsylvania
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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1. Study Identification

Unique Protocol Identification Number
NCT00080483
Brief Title
Testosterone and Growth Hormone for Bone Loss in Men
Official Title
Will Testosterone and Growth Hormone Improve Bone Structure?
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
March 2004 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypopituitarism, Hypogonadism, Growth Hormone Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Testosterone transdermally 5 g a day and somatropin subcutaneously 2 µg/kg body weight a day
Arm Title
2
Arm Type
Active Comparator
Arm Description
AndroGel transdermally 5 g a day for two years
Intervention Type
Drug
Intervention Name(s)
Testosterone plus somatropin
Intervention Description
AndoGel 5 grams transdermally a day for two years Somatropin 2 µg/kg body weight/day for two years
Intervention Type
Drug
Intervention Name(s)
testosterone
Intervention Description
AndroGel transdermally 5 g a day for two years
Primary Outcome Measure Information:
Title
MicroMRI-derived Structural (Bone Volume Fraction-BVF) of the Distal Tibia at Baseline and After One and Two Years of Treatment.
Description
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
Other Pre-specified Outcome Measures:
Title
Increased Trabecular Thickness, as Determined by Magnetic Resonance of the Distal Tibia
Time Frame
2 years
Title
Improved Architectural Parameters of Trabecular Bone Reflecting Connectivity, as Determined by Magnetic Resonance Imaging
Time Frame
2 years
Title
Increased Cortical Thickness and Cortical Density, as Determined by Peripheral Quantitative Computed Tomography of the Tibial Metaphysis
Time Frame
2 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter J. Snyder, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cecilia Lansang, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24423356
Citation
Al Mukaddam M, Rajapakse CS, Bhagat YA, Wehrli FW, Guo W, Peachey H, LeBeau SO, Zemel BS, Wang C, Swerdloff RS, Kapoor SC, Snyder PJ. Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism. J Clin Endocrinol Metab. 2014 Apr;99(4):1236-44. doi: 10.1210/jc.2013-3665. Epub 2014 Jan 13.
Results Reference
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Testosterone and Growth Hormone for Bone Loss in Men

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