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

Study Overview
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Brief Summary
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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).

Official Title
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CSP #2018 - Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)

Conditions
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Adult Growth Hormone Deficiency, Mild Traumatic Brain Injury

Intervention / Treatment
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* Drug: Somatropin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: OEF/OIF/OND Veteran Score of 1 or more on Combat Experiences sub-scale of Deployment Risk and Resilience Inventory-2 (DRRI-2) One or more TBI on Military-specific sub-domains of Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L) Score of 11 or more on QoL-AGHDA 4-week stability on any psychotropic medications 3-month stability on all other hormone treatments Able and willing to provide informed consent to participate in this study, and complete study protocol Exclusion Criteria: History of moderate or severe TBI History of neurologic disorder other than TBI with substantial impact on quality of life History of bi-polar 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 Scale (C-SSRS) suicidal ideation rating, or overt suicidal behavior in the past 6 months Contraindication to rhGH therapy Contraindication to macimorelin use Acute medical illness, active infection, cancer or decompensated chronic medical illness Evidence of substance abuse disorder in the past 6 months other than mild alcohol or cannabis use disorder; nicotine use is allowed Urine toxicology evidence of the use of an illicit drug, excluding cannabis, within the past 90 days prior to screening Scoring less than 41 on Trial I of the Test of Memory and Malingering (TOMM) BMI >35 or body weight >350 lbs Pituitary anatomy documented by an MRI using a sella protocol within the past 2 years indicating abnormalities consistent with an etiology other than mild-TBI i.e., pituitary mass Women who are pregnant or of child-bearing potential not on contraception Current use of the following: growth hormone, estrogen or estrogen-like dietary supplements, progestin, IGH-I, or chronic glucocorticoid use in supraphysiologic doses Currently enrolled in any other interventional study unless prior approval is provided by the study chairs and the study sponsor (Cooperative Studies Program)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two arm study: active drug vs placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Growth Hormone Replacement Therapy<br>Recombinant Human Growth Hormone | Drug: Somatropin<br>* Participants (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.<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Participants (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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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, 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). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months |