Anterior Pituitary Hyposecretion Syndrome, Concussion, Brain, Growth Hormone Deficiency, Hypopituitarism, Sport Injury, TBI (Traumatic Brain Injury)
Conditions
Keywords
TBI, GHD, Growth Hormone, Norditropin Flexpro, cognition disorders
Brief summary
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
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.
Interventions
BIOLOGICALGrowth Hormone
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
OTHERPlacebo
Daily self-injections by subjects: 1-year double-blind phase
Sponsors
Novo Nordisk A/S
Center for Neurological Studies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
3-D printing used to design matching cases (covers) for both the drug and placebo autoinjector pens
Intervention model description
A randomized, double-blind, placebo-controlled trial with an open-label extension
Eligibility
Sex/Gender
MALE
Age
18 Years to 76 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive functions- ANAM ( Automated Psychological Assessment Metrics) | From baseline to 1-year post-treatment | 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 |
| Cognitive functions- Working Memory | From baseline to 1-year post-treatment | 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. |
| Cognitive functions- Processing Speed | From baseline to 1-year post-treatment | 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. |
| Cognitive functions- Executive Function. | From baseline to 1-year post-treatment | 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. |
| Cognitive functions- Verbal learning and memory | From baseline to 1-year post-treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Physical function- Peak O2 consumption (Vo2 max) | One year (from baseline to 1-year post-treatment) | Measured in units of liters per minute. |
| Change in Physical function- Maximum grip strength | One year (from baseline to 1-year post-treatment) | Measured in pounds using the CAMRY Digital Hand Dynamometer |
| Change in Physical function- Isokinetic knee extension peak torque | One year (from baseline to 1-year post-treatment) | Measured using the Cybex II isokinetic dynamometer. The maximum torque is recorded in ft-lbs of force |
| Change in Physical function-DEXA measure | One year (from baseline to 1-year post-treatment) | Percent body fat and lean mass by limb and trunk |
| Adverse events | One year (from baseline to 1-year post-treatment) | To assess the incidence and severity of adverse events |
| MRI | One year (from baseline to 1-year post-treatment) | To assess changes in volumetric MRI measurements and diffusion tensor imaging (DTI) measurements |
| Change in QEEG Markers- Connectivity Measures | One year (from baseline to 1-year post-treatment) | Connectivity measures will include Pearson product moment correlation for the time series and coherence, phase synchronization and phase lag. |
| Quality of Life Assessment of Growth Hormone Deficiency in Adults | One year (from baseline to 1-year post-treatment) | 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 |
| Change in QEEG Markers- power spectra | One year (from baseline to 1-year post-treatment) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| MR imaging analysis of hypothalamus and pituitary | One year (from baseline to 1-year post-treatment) | for diagnosis of GHD or multiple anterior pituitary hormone deficiencies in GHD - professional football players with TBI |
Countries
United States
Contacts
Primary ContactVijay M Baragi, Ph.D.
Backup ContactJohn Russell
Outcome results
None listed