Growth Hormone or Sildenafil as Therapies for Fatigue in Mild- Traumatic-brain-injury (MTBI)

Three primary outcome measures are proposed:

• Perceptual fatigue as measured weekly using the Brief Fatigue Inventory (BFI) (59).
• Performance fatigue as measured at baseline and month 3, 6 and 12 using hand and leg dynamometry.
• Neuropsychological function as measured at baseline and month 12.

Secondary outcomes will include:

• Modified 6 minute walk performance as measured at baseline, and month 3, 6 and 12.
• 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.
• Sleep quality using the Pittsburgh Sleep Quality Index (PSQI), baseline, and month 3, 6, and 12.
• Multidimensional fatigue using Multidimensional Fatigue Symptom Inventory (MFSI) at baseline, and month 3, 6 and 12.
• 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.
• Physical Activity, measured daily using accelerometry.
• Cerebral blood oxygen saturation measured at baseline and month 12.
• Leg blood flow measured at baseline, and month 3, 6 and 12.
• Blood Hormones at baseline and month 3, 6 and 12.
• Characterization of brain tissue using structural, "resting state" and diffusion functional MR at baseline and month 3, 6, and 12.
• Indirect calorimetry measured at baseline and month 3, 6 and 12.

Inclusion criteria

Male or female with a diagnosis of mild TBI and 6 month post-injury. Age 18 to 60 years. Complaint of fatigue, with score of 3 or greater on questions 1, 2, or 3 of the Brief Fatigue Inventory.

Exclusion criteria

Exclusion criteria

(general)

• Significant heart, liver, kidney, blood or respiratory disease.
• Active coronary disease.
• Pregnancy.
• Alcohol or drug abuse.
• Unable to walk unassisted.
• Diabetes mellitus and anterior pituitary abnormalities diagnosed upon screening.
• Premorbid history of psychiatric disorder.
• Premorbid history of head trauma.

Exclusion criteria

(sildenafil/placebo group)

• Use of nitrates.
• Use of alpha blockers.
• Systolic blood pressure <100 or >150, diastolic blood pressure <60 or >90. This range is smaller than the acceptable range stated in the prescribing information for sildenafil (>90/50 and <170/110).
• Peripheral vascular disease.
• Use of a phosphodiesterase 5 inhibitor.

Exclusion criteria

(growth hormone/placebo group)

• Coumadin because of the risk of bleeding with daily injections of Recombinant Human Growth Hormone (rhGH) in the growth hormone (GH) arm of the study.
• Subjects who are deficient in cortisol or thyroid at screening will be excluded until hormone abnormalities have been corrected.
• 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.