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

Inclusion Criteria:

• OEF/OIF/OND Veteran

• Score of 18 or more on Combat Experiences sub-scale of Deployment Risk andResilience Inventory-2 (DRRI-2)

• Age 21 - 55 years old

• One or more mTBI sustained during military service at least 12 months prior to thescreening date, as noted via the CRAFT survey

• GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L) andIGF-I lab values have to be less than or equal to +1 SDS at baseline

• 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, andcomplete study protocol.

Exclusion Criteria:

• History of moderate or severe TBI

• History of neurologic disorder other than TBI with substantial impact on quality oflife

• History of bipolar disorder, schizophrenia, or other concurrent psychotic disorder

• Active suicidal ideation (no plan required) as determined by a score of 2 points ormore on the Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideationrating, or overt suicidal behavior in the past 6 months

• Contraindication to rhGH therapy

• Contraindication to macimorelin use, including QTc interval >470ms

• Acute medical illness, active infection, cancer or decompensated chronic medicalillness

• Evidence of substance use disorder, -other than mild alcohol or cannabis usedisorder-, or urine toxicology evidence of the use of an illicit drug (excludingcannabis), in the past 6 months. Nicotine use is allowed.

• Score less than or equal to 41 on Trial 2 or Retention Trial of the Test of MemoryMalingering (TOMM).

• BMI > 35 or body weight > 350 lbs

• Pituitary anatomy documented by an MRI using a sella protocol within the last 2years 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 dietarysupplements, progestin, IGF-I, or chronic glucocorticoid use in supraphysiologicdoses

• Currently enrolled in any other interventional study unless prior approval isprovided by the study chairs and the study sponsor (Cooperative Studies Program)