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

The University of Texas Medical Branch, Galveston34 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

QUADRUPLE

Enrollment

Conditions

Traumatic Brain Injury

Interventions

Growth HormoneDRUG

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

SildenafilDRUG

50 mg by mouth daily

PlaceboDRUG

Placebo either injected (GH group) or orally (sildenafil group) daily for three months during crossover phase of the study

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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) 1. Significant heart, liver, kidney, blood or respiratory disease. 2. Active coronary disease. 3. Pregnancy. 4. Alcohol or drug abuse. 5. Unable to walk unassisted. 6. Diabetes mellitus and anterior pituitary abnormalities diagnosed upon screening. 7. Premorbid history of psychiatric disorder. 8. Premorbid history of head trauma. Exclusion criteria (sildenafil/placebo group) 1. Use of nitrates. 2. Use of alpha blockers. 3. 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). 4. Peripheral vascular disease. 5. Use of a phosphodiesterase 5 inhibitor. Exclusion criteria (growth hormone/placebo group) 1. 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. 2. Subjects who are deficient in cortisol or thyroid at screening will be excluded until hormone abnormalities have been corrected. 3. 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.

Locations (1)

University of Texas Medical Branch

Galveston, Texas, United States

Outcomes

Primary Outcomes

Performance fatigue as measured by using hand grip dynamometry at baseline

Hand grip exercises will be used to measure performance fatigue at baseline

Time frame: baseline

Performance fatigue as measured by using hand grip dynamometry at 3 months

Hand grip exercises will be used to measure performance fatigue after 3 months of study intervention

Time frame: 3 months

Performance fatigue as measured by using hand grip dynamometry at 6 months

Hand grip exercises will be used to measure performance fatigue after 6 months of study intervention

Time frame: 6 months

Performance fatigue as measured by using hand grip dynamometry at 12 months

Hand grip exercises will be used to measure performance fatigue after 12 months of study intervention

Time frame: 12 months

Performance fatigue as measured by using leg dynamometry at baseline

Leg exercises will be used to measure performance fatigue at baseline

Time frame: baseline

Performance fatigue as measured by using leg dynamometry at 3 months

Leg exercises will be used to measure performance fatigue after 3 months of study intervention.

Time frame: 3 months

Performance fatigue as measured by using leg dynamometry at 6 months

Leg exercises will be used to measure performance fatigue after 6 months of study intervention.

Time frame: 6 months

Performance fatigue as measured by using leg dynamometry at 12 months

Data from ClinicalTrials.gov

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