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| Name | Class |
|---|---|
| Novo Nordisk A/S | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Growth Hormone | Experimental | Norditropin® (somatropin [rDNA origin] injection) via FlexPro® 30 mg / 3ml strength auto-injector pens (Novo Nordisk Inc). |
|
| Saline | Placebo Comparator | Saline-placebo via auto-injector pens (Haselmeier Inc). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Growth Hormone | Biological | 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 |
| 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. |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| MR imaging analysis of hypothalamus and pituitary | for diagnosis of GHD or multiple anterior pituitary hormone deficiencies in GHD - professional football players with TBI | One year (from baseline to 1-year post-treatment) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Vijay M Baragi, Ph.D. | Contact | 313-228-0930. | 103 | vijay@neurologicstudies.com |
| John Russell | Contact | 3132280930 | JDR@neurologicstudies.com |
| Name | Affiliation | Role |
|---|---|---|
| Randall R Benson, MD | Vice President and Medical Director | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Neurolgoical Studies (CNS) | Recruiting | Dearborn | Michigan | 48126 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23093454 | Background | Benson RR, Gattu R, Sewick B, Kou Z, Zakariah N, Cavanaugh JM, Haacke EM. Detection of hemorrhagic and axonal pathology in mild traumatic brain injury using advanced MRI: implications for neurorehabilitation. NeuroRehabilitation. 2012;31(3):261-79. doi: 10.3233/NRE-2012-0795. | |
| 17402851 | Background | Benson RR, Meda SA, Vasudevan S, Kou Z, Govindarajan KA, Hanks RA, Millis SR, Makki M, Latif Z, Coplin W, Meythaler J, Haacke EM. Global white matter analysis of diffusion tensor images is predictive of injury severity in traumatic brain injury. J Neurotrauma. 2007 Mar;24(3):446-59. doi: 10.1089/neu.2006.0153. |
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A randomized, double-blind, placebo-controlled trial with an open-label extension
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3-D printing used to design matching cases (covers) for both the drug and placebo autoinjector pens
|
| Placebo | Other | Daily self-injections by subjects: 1-year double-blind phase |
|
| 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 |
| 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) |
| 16621325 | Background | Falleti MG, Maruff P, Burman P, Harris A. The effects of growth hormone (GH) deficiency and GH replacement on cognitive performance in adults: a meta-analysis of the current literature. Psychoneuroendocrinology. 2006 Jul;31(6):681-91. doi: 10.1016/j.psyneuen.2006.01.005. Epub 2006 Apr 18. |
| 8817729 | Background | Deijen JB, de Boer H, Blok GJ, van der Veen EA. Cognitive impairments and mood disturbances in growth hormone deficient men. Psychoneuroendocrinology. 1996 Apr;21(3):313-22. doi: 10.1016/0306-4530(95)00050-x. |
| 9618751 | Background | Deijen JB, de Boer H, van der Veen EA. Cognitive changes during growth hormone replacement in adult men. Psychoneuroendocrinology. 1998 Jan;23(1):45-55. doi: 10.1016/s0306-4530(97)00092-9. |
| 15754728 | Background | Kelestimur F, Tanriverdi F, Atmaca H, Unluhizarci K, Selcuklu A, Casanueva FF. Boxing as a sport activity associated with isolated GH deficiency. J Endocrinol Invest. 2004 Dec;27(11):RC28-32. doi: 10.1007/BF03345299. |
| 24552537 | Background | Kelly DF, Chaloner C, Evans D, Mathews A, Cohan P, Wang C, Swerdloff R, Sim MS, Lee J, Wright MJ, Kernan C, Barkhoudarian G, Yuen KC, Guskiewicz K. Prevalence of pituitary hormone dysfunction, metabolic syndrome, and impaired quality of life in retired professional football players: a prospective study. J Neurotrauma. 2014 Jul 1;31(13):1161-71. doi: 10.1089/neu.2013.3212. Epub 2014 May 8. |
| 20578825 | Background | High WM Jr, Briones-Galang M, Clark JA, Gilkison C, Mossberg KA, Zgaljardic DJ, Masel BE, Urban RJ. Effect of growth hormone replacement therapy on cognition after traumatic brain injury. J Neurotrauma. 2010 Sep;27(9):1565-75. doi: 10.1089/neu.2009.1253. |
| 21117918 | Background | Reimunde P, Quintana A, Castanon B, Casteleiro N, Vilarnovo Z, Otero A, Devesa A, Otero-Cepeda XL, Devesa J. Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj. 2011;25(1):65-73. doi: 10.3109/02699052.2010.536196. Epub 2010 Nov 30. |
| 23323993 | Background | Moreau OK, Cortet-Rudelli C, Yollin E, Merlen E, Daveluy W, Rousseaux M. Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma. 2013 Jun 1;30(11):998-1006. doi: 10.1089/neu.2012.2705. Epub 2013 Jun 5. |
| 22405763 | Background | Devesa J, Reimunde P, Devesa P, Barbera M, Arce V. Growth hormone (GH) and brain trauma. Horm Behav. 2013 Feb;63(2):331-44. doi: 10.1016/j.yhbeh.2012.02.022. Epub 2012 Mar 1. |
| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D001924 | Brain Concussion |
| D007018 | Hypopituitarism |
| D004393 | Dwarfism, Pituitary |
| D003072 | Cognition Disorders |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D016489 | Head Injuries, Closed |
| D014949 | Wounds, Nonpenetrating |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D004700 | Endocrine System Diseases |
| D004392 | Dwarfism |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D001849 | Bone Diseases, Endocrine |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D013006 | Growth Hormone |
| D019382 | Human Growth Hormone |
| D007267 | Injections |
| ID | Term |
|---|---|
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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