The purpose of this study is to determine whether growth hormone replacement therapy (GHRT) is effective versus placebo in the improvement of Quality of Life in patients with adult growth hormone deficiency (AGHD) and mild traumatic brain injury (mTBI).
OEF/OIF/OND Veteran
Score of 18 or more on Combat Experiences sub-scale of Deployment Risk and Resilience Inventory-2 (DRRI-2)
Age 21 - 55 years old
One or more mTBI sustained during military service at least 12 months prior to the screening date, as noted via the CRAFT survey.
History of moderate or severe TBI
History of neurologic disorder other than TBI with substantial impact on quality of life
History of bipolar disorder, schizophrenia, or other concurrent psychotic disorder
Active suicidal ideation (no plan required) as determined by a score of 2 points or more on the Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation rating, or overt suicidal behavior in the past 6 months.
Parallel
Somatropin
DrugParticipants (n=172) will be randomized in a 1:1 ratio to rhGH (n=86) versus placebo (n=86) for six months, stratified by participating site. Both study participants and the study team will be blinded to treatment assignment. All participants will complete in-clinic follow-ups at Days 14, 40, 65, and 90 (3 months) and at day 180 (6 months). The primary outcome will be the mean difference in QoL-AGHDA scores between treatment arms at 6 months follow-up. Patients will discontinue the study intervention at 6 months, and will be followed-up two weeks subsequent, in order to assure patient safety and wellness, and to ensure maximal facilitation of patient transition back into routine care.
Placebo
Other interventionParticipants (n=172) will be randomized in a 1:1 ratio to rhGH (n=86) versus placebo (n=86) for six months, stratified by participating site. Both study participants and the study team will be blinded to treatment assignment. All participants will complete in-clinic follow-ups at Days 14, 40, 65, and 90 (3 months) and at day 180 (6 months). The primary outcome will be the mean difference in QoL-AGHDA scores between treatment arms at 6 months follow-up. Patients will discontinue the study intervention at 6 months, and will be followed-up two weeks subsequent, in order to assure patient safety and wellness, and to ensure maximal facilitation of patient transition back into routine care.
QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults)
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).
Body Composition
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.
Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21)
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.
Cognition
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.
Severity of Fatigue Symptoms
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.
Sleep Quality
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.
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