Brain and Gut Plasticity in Mild TBI Following Growth Hormone Therapy
Brain and Gut Plasticity in Mild TBI Following Growth Hormone Therapy
Patients with a history of mild traumatic brain injury (mTBI) and abnormal growth hormone
 secretion, as measured by glucagon stimulation test, will be treated with replacement growth
 hormone therapy for a period of 6 months. Testing of cognition, exercise, fatigue, brain
 activation and morphology, body composition and measurements of quality of life will be
 performed before and after the treatment period. Fecal sampling for characterization of the
 GI microbiome will occur monthly over the treatment period. Each mTBI subject will be
 required to enroll with an eligible control from their household that will also provide fecal
 samples monthly during the treatment period of their mTBI partner. GI microbiomes will be
 compared between mTBI patients and their household controls at baseline as well as over the
 treatment period.
The investigators will study subjects (aged 18-70 years) with a history of mild TBI (n=25)
 and their household controls (aged 18-70 years) (n=25). mTBI subjects will undergo a 6-month
 intervention of rhGH therapy. Household controls will be asked to participate in
 questionnaires, blood draws (amino acid analysis), and fecal sampling (GI microbiome
 analysis). Household controls will not receive any growth hormone treatment.

 mTBI group

 All patients presenting with a prior mTBI will undergo a phone pre-screen including the Brief
 Fatigue Inventory (BFI) questions 1-3. If they score ≥ 3 on any BFI questions 1-3, and are
 interested in participating in the study, they will be scheduled for a formal consenting and
 medical screening at the UTMB Clinical Research Center (CRC). During the medical screening,
 eligibility will be confirmed and a glucagon stimulation test (GST) will be performed. A
 glucagon stimulation with a growth hormone peak of <10 ng/mL is required to qualify for
 enrollment.

 Household control group

 All household controls will undergo a phone pre-screen and if interested in participating in
 the study, will be scheduled for a formal consenting and medical screening at the UTMB
 Clinical Research Center (CRC).

 Experimental Protocol.

 mTBI Group

 Before and at completion (month 6) of the rhGH intervention, mTBI subjects will report to the
 UTMB Institute for Translational Sciences (ITS) Clinical Research Center (CRC) for testing,
 which will consist of cognitive function assessment (MoCA), determination of brain morphology
 and connectivity using fMRI, determination of lean mass and fat mass using DEXA, resting
 energy expenditure, functional testing including leg strength and 6 minute walk test, fatigue
 measurements, and questionnaires of mood and quality of life, gastrointestinal health, sleep,
 and food preferences. Blood sampling for measurement of amino acid levels, hormones, and
 metabolites will be drawn before and 90 minutes (+/- 10 minutes) after a standardized meal.
 In addition, fecal samples for analysis of the GI microbiome will be collected monthly for
 the duration of the study. Insulin Growth Factor 1 (IGF-1) levels will monitored at a month 1
 safety visit for all mTBI subjects. The month 1 safety visit will occur +/- 5 days from the
 expected date based on the baseline study visit. The monthly fecal sampling will occur +/- 7
 days from the expected date based on the baseline study visit. The month 6 post study will
 occur +/- 7 days from the expected date based on the baseline study visit. A member of the
 study team will contact the subject each month to coordinate fecal sample transport to UTMB,
 check for adverse events and overall well-being, and ensure compliance and ongoing consent.

 Household control group

 Before and at completion (month 6) of the rhGH intervention of their mTBI subject partners,
 household controls will report to the UTMB Institute for Translational Sciences (ITS)
 Clinical Research Center (CRC) for testing, which will consist of questionnaires of food
 preferences and gastrointestinal health and blood sampling for measurement of amino acid
 levels, hormones, and metabolites which will be drawn before and 90 minutes (+/ 10 minutes)
 after a standardized meal. In addition, fecal samples for the analysis of the GI microbiome
 will be collected monthly for the duration of the study, as well as questionnaire assessing
 gastrointestinal health. The monthly fecal sampling will occur +/- 7 days from the expected
 date based on the baseline study visit. The post study (month 6) will occur +/- 7 days from
 the expected date based on the baseline study visit. A member of the study team will contact
 the subject each month to coordinate fecal sample transport to UTMB, check for adverse events
 and overall well-being, and ensure compliance and ongoing consent.
mTBI Inclusion criteria

 1. Male or female with a diagnosis of mild TBI.

 2. At least 6-month post-injury.

 3. Ages 18 to 70 years.

 4. Lives in same household as paired control that meets inclusion/exclusion criteria.

 5. Participant is willing and able to give informed consent for participation in the
 study.

 mTBI Exclusion criteria

 1. Unable to walk unassisted.

 2. Significant heart, liver, kidney, blood or respiratory disease.

 3. History of chest pain or coronary heart disease.

 4. Uncontrolled Diabetes mellitus.

 5. Any history of a recently (12 months) diagnosed cancer other than a skin cancer
 (excluding melanoma).

 6. Recent (within 6 months) treatment with anabolic steroids or corticosteroids.

 7. Current alcohol or drug abuse.

 8. Premorbid history of psychiatric disorder.

 9. Premorbid history of head trauma.

 10. Pregnancy or become pregnant during the trial.

 11. Coumadin because of the risk of bleeding with daily injections of rhGH.

 12. Subjects who are deficient in cortisol or thyroid at screening will be excluded until
 hormone abnormalities have been corrected.

 13. Subjects with chronic pain who are being managed with narcotics will be excluded as
 the effects of central nervous system depressants may interfere with study test
 results.

 14. Subjects with a history of inflammatory bowel disease, Celiac disease or active
 diverticular disease.

 15. Subjects with a history of oral or IV antibiotics within the past 3 months.

 Household Control Inclusion criteria

 1. Ages 18 to 70 years.

 2. Lives in same household as paired mTBI subject that meets inclusion/exclusion
 criteria.

 3. Participant is willing and able to give informed consent for participation in the
 study.

 Household Control Exclusion criteria

 1. Significant heart, liver, kidney, blood or respiratory disease.

 2. Uncontrolled Diabetes mellitus.

 3. Any history of a recently (12 months) diagnosed cancer other than a skin cancer
 (excluding melanoma).

 4. Recent (within 6 months) treatment with anabolic steroids or corticosteroids.

 5. Current alcohol or drug abuse.

 6. Premorbid history of psychiatric disorder.

 7. Premorbid history of head trauma.

 8. Pregnancy or become pregnant during the trial.

 9. Subjects who are deficient in thyroid at screening will be excluded until thyroid
 hormone is replaced.

 10. Subjects with a history of inflammatory bowel disease, Celiac disease or active
 diverticular disease.

 11. Subjects with a history of oral or IV antibiotics within the past 3 months.