Growth Hormone Replacement Therapy for Retried Professional Football Players

NCT04121780 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: UTN: U1111-1201-5972
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

TBI; GHD; Growth Hormone; Norditropin Flexpro; cognition disorders

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (9)

• Quality of Life Assessment of Growth Hormone Deficiency in Adults

  One year (from baseline to 1-year post-treatment)

• Change in QEEG Markers- power spectra

  One year (from baseline to 1-year post-treatment)

• Change in QEEG Markers- Connectivity Measures

  One year (from baseline to 1-year post-treatment)

• MRI

  One year (from baseline to 1-year post-treatment)

• Change in Physical function- Peak O2 consumption (Vo2 max)

  One year (from baseline to 1-year post-treatment)

Other Outcomes (1)

• MR imaging analysis of hypothalamus and pituitary

  One year (from baseline to 1-year post-treatment)

Study Arms (2)

Growth Hormone

EXPERIMENTAL

Norditropin® (somatropin \[rDNA origin\] injection) via FlexPro® 30 mg / 3ml strength auto-injector pens (Novo Nordisk Inc).

Biological: Growth Hormone

Saline

PLACEBO COMPARATOR

Saline-placebo via auto-injector pens (Haselmeier Inc).

Other: Placebo

Interventions

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

Also known as: Norditropin® (somatropin [rDNA origin] injection)

Growth Hormone

Placebo OTHER

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

Saline

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Center for Neurological Studies: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Center for Neurolgoical Studies (CNS)

Dearborn, Michigan, 48126, United States

RECRUITING

Related 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.

  PMID: 23093454 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.

  PMID: 17402851 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.

  PMID: 16621325 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.

  PMID: 8817729 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.

  PMID: 9618751 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.

  PMID: 15754728 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.

  PMID: 24552537 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.

  PMID: 20578825 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.

  PMID: 21117918 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.

  PMID: 23323993 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.

  PMID: 22405763 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Brain Concussion; Hypopituitarism; Dwarfism, Pituitary; Cognition Disorders

Interventions

Growth Hormone; Human Growth Hormone; Injections

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Head Injuries, Closed; Wounds, Nonpenetrating; Pituitary Diseases; Hypothalamic Diseases; Endocrine System Diseases; Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Randall R Benson, MD

  Vice President and Medical Director

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vijay M Baragi, Ph.D.

CONTACT

313-228-0930.; vijay@neurologicstudies.com

John Russell

CONTACT

3132280930; JDR@neurologicstudies.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 3-D printing used to design matching cases (covers) for both the drug and placebo autoinjector pens
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized, double-blind, placebo-controlled trial with an open-label extension

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 10, 2019
• Study Start: October 8, 2019
• Primary Completion: March 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)