Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)

25 question survey on quality of life; The primary objective of CSP #2018 is to determine the efficacy of rhGH, given daily for 6 months, versus placebo to improve QoL, as measured by difference in mean QoL-AGHDA score, among Veterans with a history of mTBI and AGHD (primary outcome). The primary hypothesis is that the investigators, compared to placebo, patients treated with rhGH will exhibit a 3.5-point lower mean score (higher quality of life) in QoL-AGHDA at 6 months. QoL-AGHDA: minimum score=0 (high QoL: best outcome); maximum score=25 (low QoL: worst outcome).

DEXA (Dual-Energy x-ray absorptiometry); The secondary objective of CSP #2018 is to investigate the efficacy of rhGH vs placebo on long-term surrogate outcomes: a) body composition, assessed through dual-energy x-ray absorptiometry (DEXA) and b) cardiometabolic risk factors including lipids, autonomic function, and highly sensitive C-reactive protein. The specific hypotheses for these outcomes are that compared to placebo there will be a 4.5% mean reduction in total truncal body fat percentage and a mean reduction of 10 mg/dL in LDL serum levels after 6 months of treatment and follow-up of rhGH.

Tertiary endpoint of interest: Depressive and anxiety symptoms measured by DASS-21 scores and post-traumatic stress symptoms measured by the PTSD Checklist for DSM-5 are expected to be lower (improved) within the rhGH arm after 6 months of therapy compared to the placebo arm.

Tertiary endpoint of interest: Cognitive functioning will be assessed the Color Word Interference Test for cognitive flexibility and inhibition; the Digit Span test for working memory capacity; the Trail Making Test for processing speed, cognitive flexibility, and attention; the Grooved Pegboard for fine motor control and coordination; the Letter Fluency Test for verbal fluency and executive function; and the Rey Auditory Verbal Learning Test for verbal learning, memory, and attention. All test scores will be converted to z-scores, which standardize the results based on the mean and standard deviation of the normative sample, then averaged to generate a composite score, with higher scores indicating better performance relative to the normative sample. Both, individual test scores and the composite score will be analyzed to evaluate whether six-month recombinant human Growth Hormone treatment has any significant effect on cognitive performance.

Tertiary endpoint of interest: Severity of fatigue symptoms measured by the Patient Health Questionnaire 15-item somatic symptom severity scale PHQ-15 are expected to improve after 6 months of rhGH therapy compared to the placebo arm.

Exploratory objective and hypothesis: Sleep quality as measured by the Pittsburgh Sleep Quality Index Score (PSQI). We hypothesize that subjective measures of sleep quality and daytime sleepiness will significantly improve in the active arm compared to placebo.

Exploratory objective and hypothesis: Chronic pain assessed using the Defense Veterans Pain Report System-II (DVPRS-II); hypothesize that pain severity and pain interference with activities of daily living will be significantly reduced among participants receiving GHRT compared to placebo.