Growth Hormone or Sildenafil as Therapies for Fatigue in Mild- Traumatic-brain-injury (MTBI)
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Fatigue
Study type: Interventional
Phase: Phase 1

Summary: 
      The overall goal is to determine whether perceptual or performance fatigue can be reduced in
      MTBI patients with and without growth hormone (GH) deficiency by treating them in a crossover
      fashion based upon GH status.

      A battery of functional, fatigue, cognitive, imaging and blood flow tests will be performed
      to assess the efficacy of the two drug interventions, Growth hormone and Sildenafil.
    

Detailed description: 
      Three primary outcome measures are proposed:

        1. Perceptual fatigue as measured weekly using the Brief Fatigue Inventory (BFI) (59).

        2. Performance fatigue as measured at baseline and month 3, 6 and 12 using hand and leg
           dynamometry.

        3. Neuropsychological function as measured at baseline and month 12.

      Secondary outcomes will include:

        1. Modified 6 minute walk performance as measured at baseline, and month 3, 6 and 12.

        2. Mood and quality of life using the Profile of Mood States, Quality of Life Assessment of
           GH Deficiency in Adults questionnaire, and a grief assessment (60) (POMS), measured at
           baseline, and month 3, 6, and 12.

        3. Sleep quality using the Pittsburgh Sleep Quality Index (PSQI), baseline, and month 3, 6,
           and 12.

        4. Multidimensional fatigue using Multidimensional Fatigue Symptom Inventory (MFSI) at
           baseline, and month 3, 6 and 12.

        5. Skeletal muscle mass, as derived from lean body mass determinations, using dual energy
           X-ray absorptiometry (iDEXA) at baseline, and month 3, 6, and 12.

        6. Physical Activity, measured daily using accelerometry.

        7. Cerebral blood oxygen saturation measured at baseline and month 12.

        8. Leg blood flow measured at baseline, and month 3, 6 and 12.

        9. Blood Hormones at baseline and month 3, 6 and 12.

       10. Characterization of brain tissue using structural, "resting state" and diffusion
           functional MR at baseline and month 3, 6, and 12.

       11. Indirect calorimetry measured at baseline and month 3, 6 and 12.
    

Intervention name(s): Growth Hormone; Sildenafil; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 0.4 mg/day injected subcutaneously for one month then increased to 0.6 mg/day for two months during crossover phase. After crossover phase, 0.6 mg/day for six months; 50 mg by mouth daily; Placebo either injected (GH group) or orally (sildenafil group) daily for three months during crossover phase of the study
Other intervention name(s): Genotropin; Viagra
Intervention MeSH terms: Sildenafil Citrate; Hormones
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: mild traumatic brain injury; growth hormone; fatigue; sildenafil; neurology