Growth Hormone Replacement Therapy for Retried Professional Football Players

Growth Hormone Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04121780
• Other study ID #: UTN: U1111-1201-5972
• Status: Recruiting
• Phase: Phase 2
• Start date: October 8, 2019
• Est. completion date: September 2026

Study information

• Verified date: February 2023
• Source: Center for Neurological Studies
• Contact: Vijay M Baragi, Ph.D.
• Phone: 313-228-0930.
• Email: vijay[@]neurologicstudies.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: September 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 76 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anterior Pituitary Hyposecretion Syndrome
• Athletic Injuries
• Brain Concussion
• Brain Injuries
• Brain Injuries, Traumatic
• Concussion, Brain
• Dwarfism, Pituitary
• Growth Hormone Deficiency
• Hypopituitarism
• Sport Injury
• TBI (Traumatic Brain Injury)
• Wounds and Injuries

Intervention

Biological:
• Growth 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

Other:
• Placebo
Daily self-injections by subjects: 1-year double-blind phase

Locations

Country	Name	City	State
United States	Center for Neurolgoical Studies (CNS)	Dearborn	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Center for Neurological Studies	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	MRI	To assess changes in volumetric MRI measurements and diffusion tensor imaging (DTI) measurements	One year (from baseline to 1-year post-treatment)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Adverse events	To assess the incidence and severity of adverse events	One year (from baseline to 1-year post-treatment)

External Links

•   CNS webpage for NFL study