TBI (Traumatic Brain Injury)Phase 2NCT04121780
Growth Hormone Replacement Therapy for Retried Professional Football Players
A Phase 2 study testing Growth Hormone in people with TBI (Traumatic Brain Injury) and Concussion, Brain, run by Center for Neurological Studies at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 76 years, men only
- Conditions the study is for
- TBI (Traumatic Brain Injury), Concussion, Brain, Sport Injury
- What is being tested?
- Growth Hormone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2019to Sep 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 76 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Center for Neurolgoical Studies (CNS)
Dearborn, Michigan, 48126
Vijay Baragi, Ph.D., 313-228-0930, vijay@neurologicstudies.com
John Russell, 3132280930, JDR@neurologicstudies.com
About this study
Official title: Interventional Study of Growth Hormone Replacement Therapy in Retired Professional Football Players With Growth Hormone Deficiency
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).
Read the 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.
- Conditions
- TBI (Traumatic Brain Injury), Concussion, Brain, Sport Injury, Anterior Pituitary Hyposecretion Syndrome, Hypopituitarism, Growth Hormone Deficiency
- Being tested
- Growth Hormone, Placebo
- Keywords
- TBI, GHD, Growth Hormone, Norditropin Flexpro, cognition disorders
- Medical subject headings
- Brain Injuries, Traumatic, Brain Concussion, Hypopituitarism, Dwarfism, Pituitary, Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Growth HormoneBiological
Also called Norditropin® (somatropin [rDNA origin] injection)
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
PlaceboOther
Daily self-injections by subjects:
1-year double-blind phase
| Study group | Role | What they receive |
|---|---|---|
| Growth Hormone | Experimental | Norditropin® (somatropin [rDNA origin] injection) via FlexPro® 30 mg / 3ml strength auto-injector pens (Novo Nordisk Inc). Receives: Biological: Growth Hormone |
| Saline | Placebo comparator | Saline-placebo via auto-injector pens (Haselmeier Inc). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: From baseline to 1-year post-treatment
Secondary outcomes (9)
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
Measured: 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.
Measured: 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.
Measured: One year (from baseline to 1-year post-treatment)
MRI
To assess changes in volumetric MRI measurements and diffusion tensor imaging (DTI) measurements
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: One year (from baseline to 1-year post-treatment)
Adverse events
To assess the incidence and severity of adverse events
Measured: One year (from baseline to 1-year post-treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start8 Oct 2019
- Primary completionMar 2025 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for TBI (Traumatic Brain Injury)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, double-blind, placebo-controlled trial with an open-label extension
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Center for Neurological Studies
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Randall R Benson, MD, Principal investigator, Vice President and Medical Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04121780
- Sponsor's protocol ID
- UTN: U1111-1201-5972
- Status last verified
- Feb 2023
- First submitted
- 25 Sep 2019
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23093454Benson 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.
PubMed 17402851Falleti 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.
PubMed 16621325Deijen 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.
PubMed 8817729Deijen 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.
PubMed 9618751Kelestimur 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.
PubMed 15754728Kelly 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.
PubMed 24552537High 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.
PubMed 20578825Reimunde 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.
PubMed 21117918Moreau 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.
PubMed 23323993Devesa 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.
PubMed 22405763