Brain and Gut Plasticity in Mild TBI or Post-acute COVID Syndrome Following Growth Hormone Therapy
Condition: Traumatic Brain Injury; Fatigue; Cognitive Impairment; COVID-19
MeSH terms: COVID-19; Post-Acute COVID-19 Syndrome; Brain Injuries; Brain Injuries, Traumatic; Fatigue; Cognitive Dysfunction
Study type: Interventional
Phase: Phase 3

Summary: 
      Patients with a history of mild traumatic brain injury (mTBI) or post acute sequelae of
      SARS-CoV-2 (PASC) 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 (mTBI)
      or 9 months (PASC). 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. Control subjects will be enrolled and will provide fecal samples
      monthly for 6 months. GI microbiomes will be compared between mTBI patients, PASC patients
      and controls at baseline as well as over the treatment period.
    

Detailed description: 
      The investigators will study subjects (aged 18-70 years) with a history of mild TBI (n=25),
      post-acute sequelae of SARS-CoV-2 (PASC) (n=25)and healthy controls (n=25). mTBI subjects
      will undergo a 6-month intervention of rhGH therapy. PASC subjects will undergo a 9-month
      intervention of rhGH therapy. Controls will be asked to participate in questionnaires, blood
      draws (amino acid analysis), and fecal sampling (GI microbiome analysis). 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.

      PASC group

      All patients presenting with PASC 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.

      Control group

      All 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.

      PASC Group

      Before and at month 6 of the rhGH intervention, PASC 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 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. PASC subjects will continue on rhGH treatment for an additional 3 months. GI
      microbiome sampling and questionnaires will occur at month 9 and month 12. PASC subjects will
      have an repeat glucagon stimulation test (GST) to determine growth hormone status at month
      12. 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.

      Control group

      Before and at month 6, 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.
    

Intervention name(s): Somatropin
Intervention type(s): Drug
Intervention description(s): Genotropin given by injection
Other intervention name(s): Genotropin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: mTBI patients will be in the growth hormone arm PASC patients will be in the growth hormone arm Control subjects will be in the control arm
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: growth hormone; Traumatic Brain injury; concussion; mTBI; fatigue; cognitive impairment; BIAFAC; COVID-19; post-COVID syndrome; long hauler COVID-19; post-acute sequelae of SARS-CoV-2