Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
mTBI patients will be in the growth hormone arm Household control subjects will be in the control arm
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
mTBI subjects
mTBI subjects will receive recombinant human growth hormone replacement therapy daily for 6 months. Drug: recombinant human growth hormone (rhgH); somatropin, Genotropin Dose: month 0 - month 1 will be dosed at 0.4 mg / day month 1 - month 6 will be dosed at 0.6 mg / day
  • Drug: Somatropin
    Genotropin given by injection
    Other names:
    • Genotropin
No Intervention
Household Control Subjects
household control subjects will not receive any intervention.

Recruiting Locations

University of Texas Medical Branch
Galveston, Texas 77555
Contact:
Kate M Randolph, BS
409-772-8126
kmrandol@utmb.edu

More Details

NCT ID
NCT03554265
Status
Recruiting
Sponsor
The University of Texas Medical Branch, Galveston

Study Contact

Kate M Randolph, BS
409-772-8126
kmrandol@utmb.edu

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.