Growth Hormone Replacement Therapy for Retried Professional Football Players

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-group trial with an open-label extension to evaluate the efficacy of growth hormone (GH) on cognitive functions of retired professional football players with growth hormone deficiency (GHD).

Detailed Description
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GHD is the most common anterior pituitary abnormality after traumatic brain injury (TBI). It can occur as a result of either direct pituitary or indirect hypothalamic injury. Sports-related repetitive head trauma might induce pituitary dysfunction, and in particular, isolated GHD. Growth hormone replacement therapy (GHRT) has long been known to have a beneficial effect on body composition and exercise capacity. However, it has recently been shown that GHRT also benefits the brain. The primary objective of the current study is to assess the effect of GH on memory, executive function and attention domains of cognitive function in GHD- professional football players with TBI. The study will also utilize the adult growth hormone deficiency assessment (AGHDA) questionnaire, quantitative electroencephalogram (QEEG) and magnetic resonance imaging (MRI) techniques, respectively, to measure the quality of life (QoL), electrical activity and structural changes in the brain that may correspond to cognitive deficits.

Official Title
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Interventional Study of Growth Hormone Replacement Therapy in Retired Professional Football Players With Growth Hormone Deficiency

Conditions
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TBI (Traumatic Brain Injury), Concussion, Brain, Sport Injury, Anterior Pituitary Hyposecretion Syndrome, Hypopituitarism, Growth Hormone Deficiency

Intervention / Treatment
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* Biological: Growth Hormone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject is willing to provide a signed and dated informed consent indicating that he understands the purpose and procedures required for the study and is willing to participate in the study. Former NFL player At least one year since retirement from football Less than 76 years of age Diagnosis of GHD on clinical grounds by a neurologist and an endocrinologist GHD Exclusion Criteria: History of pre-existing brain disease other than concussion or TBI History of a premorbid disabling condition that interferes with outcome assessments Contraindication to GH therapy Type I and II Diabetes mellitus Active malignant disease Acute critical illness, heart failure, or acute respiratory failure Subjects who are deficient in cortisol, testosterone or thyroid at screening will be excluded until hormone abnormalities have been corrected.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double-blind, placebo-controlled trial with an open-label extension
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Growth Hormone<br>Norditropin® (somatropin [rDNA origin] injection) via FlexPro® 30 mg / 3ml strength auto-injector pens (Novo Nordisk Inc). | Biological: Growth Hormone<br>* Daily self-injections by subjects: 1-year double-blind phase; 6-month open-label extension for those who received placebo during the double-blind phase<br>* Other names: Norditropin® (somatropin [rDNA origin] injection);|
| Placebo Comparator: Saline<br>Saline-placebo via auto-injector pens (Haselmeier Inc). | Other: Placebo<br>* Daily self-injections by subjects: 1-year double-blind phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive functions- Working Memory | To assess change in working memory from base line to 1 yr post-treatment. Working memory will be reported as an index score based on scaled scores for the digit span subtest and symbol span subtest. Index scores have a mean of 100 and a standard deviation of 15. The typical range of index score is 45 to 155. Higher scores reflect better functioning. The scaled scores have a mean of 10 and a standard deviation of 3. Scores range from 1 to 19. Higher scores reflect better functioning. | From baseline to 1-year post-treatment | 
| Cognitive functions- Processing Speed | To assess change in Processing Speed from baseline to 1 yr post-treatment. Processing speed will be reported as an index score based on scaled scores of digit symbol subtest and symbol search subtest. Index scores have a mean of 100 and a standard deviation of 15. The typical range of index score is 45 to 155. Higher scores reflect better functioning. The scaled scores have a mean of 10 and a standard deviation of 3. Scores range from 1 to 19. Higher scores reflect better functioning. Trail Making Test A will also be used to assess processing speed. Reported as T-score. Higher scores reflect better performance. | From baseline to 1-year post-treatment | 
| Cognitive functions- Executive Function. | To assess change in Executive Function from baseline to 1 yr post-treatment. Trail Making Test B and verbal fluency (letter and category) will be used to assess executive function. Reported as T-score. T scores have a mean of 50 and a standard deviation of 10. Scores range from 13 to 87. Higher scores reflect better performance. | From baseline to 1-year post-treatment | 
| Cognitive functions- Verbal learning and memory | To assess change in Verbal learning and memory from baseline to 1 yr post-treatment. California verbal learning test will be used to assess this outcome measure. Reported as a standard score with a mean of 0 and a standard deviation of 1. Scores range from -0.5 to +5.0. Higher scores reflect better performance. | From baseline to 1-year post-treatment | 
| Cognitive functions- ANAM ( Automated Psychological Assessment Metrics) | To assess change in ANAM from baseline to 1 yr post-treatment. ANAM Test System- Core Battery will be used to assess this outcome measure. Reported as a standard score | From baseline to 1-year post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Assessment of Growth Hormone Deficiency in Adults | This measure includes a scale: It is based on the Adult Growth Hormone Deficiency Assessment (AGHDA) QoL questionnaire. It consists of 25 yes/no questions. Score ranges from 0-25 with number of yes responses indicating score. A score of 8 or higher is typical of untreated adult GH deficiency. Treatment, on an average, results in a decrease of 2.5 to 3 points on the scale at one year | One year (from baseline to 1-year post-treatment) | 
| Change in QEEG Markers- power spectra | Spectral markers include delta (1-5-2.5 Hz), theta (3.5-7.5 Hz), alpha (7.5-12.5 Hz), alpha 1 (7.5-10.0 Hz), alpha 2 (10.0-12.5 Hz), beta 1 (12.5- 25.0 Hz) , beta 2 (25.0-35.0 Hz), gamma (35.0- 50.0 Hz). The power will be averaged over all electrode sites as absolute and relative power. | One year (from baseline to 1-year post-treatment) | 
| Change in QEEG Markers- Connectivity Measures | Connectivity measures will include Pearson product moment correlation for the time series and coherence, phase synchronization and phase lag. | One year (from baseline to 1-year post-treatment) | 
| MRI | To assess changes in volumetric MRI measurements and diffusion tensor imaging (DTI) measurements | One year (from baseline to 1-year post-treatment) | 
| Change in Physical function- Peak O2 consumption (Vo2 max) | Measured in units of liters per minute. | One year (from baseline to 1-year post-treatment) | 
| Change in Physical function- Maximum grip strength | Measured in pounds using the CAMRY Digital Hand Dynamometer | One year (from baseline to 1-year post-treatment) | 
| Change in Physical function- Isokinetic knee extension peak torque | Measured using the Cybex II isokinetic dynamometer. The maximum torque is recorded in ft-lbs of force | One year (from baseline to 1-year post-treatment) | 
| Change in Physical function-DEXA measure | Percent body fat and lean mass by limb and trunk | One year (from baseline to 1-year post-treatment) | 
| Adverse events | To assess the incidence and severity of adverse events | One year (from baseline to 1-year post-treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TBI, GHD, Growth Hormone, Norditropin Flexpro, cognition disorders