Clinical trial NCT04121780: Growth Hormone Replacement Therapy for Retried Professional Football Players
Official title: Interventional Study of Growth Hormone Replacement Therapy in Retired Professional Football Players With Growth Hormone Deficiency
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
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
Lead sponsor: Center for Neurological Studies
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2019-10-10
Enrollment: 42
Sex: MALE
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, double-blind, placebo-controlled trial with an open-label extension
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cognitive functions- Working Memory
timeFrame: From baseline to 1-year post-treatment
measure: Cognitive functions- Processing Speed
timeFrame: From baseline to 1-year post-treatment
measure: Cognitive functions- Executive Function.
timeFrame: From baseline to 1-year post-treatment
measure: Cognitive functions- Verbal learning and memory
timeFrame: From baseline to 1-year post-treatment
measure: Cognitive functions- ANAM ( Automated Psychological Assessment Metrics)
timeFrame: From baseline to 1-year post-treatment
Secondary outcomes:
measure: Quality of Life Assessment of Growth Hormone Deficiency in Adults
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Change in QEEG Markers- power spectra
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Change in QEEG Markers- Connectivity Measures
timeFrame: One year (from baseline to 1-year post-treatment)
measure: MRI
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Change in Physical function- Peak O2 consumption (Vo2 max)
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Change in Physical function- Maximum grip strength
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Change in Physical function- Isokinetic knee extension peak torque
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Change in Physical function-DEXA measure
timeFrame: One year (from baseline to 1-year post-treatment)
measure: Adverse events
timeFrame: One year (from baseline to 1-year post-treatment)
Other outcomes:
measure: MR imaging analysis of hypothalamus and pituitary
timeFrame: One year (from baseline to 1-year post-treatment)
Locations:
city: Dearborn
country: United States
facility: Center for Neurolgoical Studies (CNS)
state: Michigan
Study officials:
affiliation: Vice President and Medical Director
name: Randall R Benson, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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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.
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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.
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