Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury.
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Intervention: Recombinant human Growth Hormone; Placebo
Intervention description: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements; SC injection daily
Intervention MeSH terms: Hormones
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Mood disorders; Cognitive disorders; Fatigue; Metabolic disorders

Summary:

      Growth Hormone (GH) deficiency, defined by insufficient GH response to a variety of
      stimulating compounds, is found in 20-35% of adults who suffer traumatic brain injuries (TBI)
      requiring inpatient rehabilitation1. However, there is no accepted gold standard for
      diagnosing GH deficiency in this population. Further, the major effector molecule of the
      somatotropic axis, Insulin-Like Growth Factor-1 (IGF-1) has recently been recognized as an
      important neurotrophic agent. Since most repair and regeneration after TBI occurs within the
      first few months after injury, absolute or relative deficiencies of GH and IGF-1 in the
      subacute period after TBI are potentially important factors why some patients fail to make a
      good functional recovery. The proposed study is a randomized, double-blind,
      placebo-controlled trial of rhGH, starting at 1 month post TBI, continuing for 6 months.

      This study has one primary hypothesis, that treatment with recombinant human Growth Hormone
      (rhGH) in the subacute period after TBI results in improved functional outcome 6 months after
      injury. As secondary hypotheses, we will investigate what is the optimal method to diagnose
      GH deficiency in TBI survivors and study the relationship between GH deficiency and
      insufficiency and functional recovery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Non-penetrating TBI

          2. Age 18 - 50 years.

          3. Admission to a North Texas Traumatic Brain Injury Model System-affiliated
             rehabilitation unit within 8 weeks of injury. Enrollment in TBI-MS database not
             required.

          4. Randomization within 2 - 10 weeks of injury.

          5. Rancho Los Amigos Rating IV or better at the time of randomization. Should not be at
             Rancho IV level for more than 4 weeks before randomization.

          6. GH deficiency diagnosed by either of the following two criteria:

               1. . Peak GH response to L-arginine stimulation test < 1.4 microg/L; or

               2. . Plasma IGF-1 level 1 SD below the expected median for age and body weight.

          7. Availability of caregiver to oversee administration of medications.

          8. Reasonable expectation for completion of outcome measures

          9. Residence inside the United States

        Exclusion Criteria:

          1. History of pre-existing neurologic disease (such as epilepsy, brain tumors,
             meningitis, cerebral palsy, encephalitis, brain abscesses, vascular malformations,
             cerebrovascular disease, Alzheimer's disease, multiple sclerosis, or HIV-encephalitis)

          2. History of premorbid disabling condition that interfere with outcome assessments

          3. Contraindication to rhGH therapy. (hypersensitivity to rhGH or any of the components
             of the supplied product, including metacresol, glycerin, or benzyl alcohol)

          4. Penetrating traumatic brain injury

          5. Diabetes mellitus.

          6. Obesity (BMI > 30).

          7. Active infection.

          8. Active malignant disease.

          9. Acute critical illness, heart failure, or acute respiratory failure

         10. Previous hospitalization for TBI > 1 day

         11. Membership in a vulnerable population (prisoner)

         12. Pregnancy. Women of childbearing age will be given a pregnancy test during screening
             to exclude pregnancy.

         13. Lactating females