Clinical trial NCT02114775: Growth Hormone or Sildenafil as Therapies for Fatigue in Mild- Traumatic-brain-injury (MTBI)
Official title: Growth Hormone or Sildenafil as Therapies for Fatigue in MTBI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Traumatic Brain Injury
Keywords: mild traumatic brain injury
growth hormone
fatigue
sildenafil
neurology
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2014-04-15
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Performance fatigue as measured by using hand grip dynamometry at baseline
timeFrame: baseline
measure: Performance fatigue as measured by using hand grip dynamometry at 3 months
timeFrame: 3 months
measure: Performance fatigue as measured by using hand grip dynamometry at 6 months
timeFrame: 6 months
measure: Performance fatigue as measured by using hand grip dynamometry at 12 months
timeFrame: 12 months
measure: Performance fatigue as measured by using leg dynamometry at baseline
timeFrame: baseline
measure: Performance fatigue as measured by using leg dynamometry at 3 months
timeFrame: 3 months
measure: Performance fatigue as measured by using leg dynamometry at 6 months
timeFrame: 6 months
measure: Performance fatigue as measured by using leg dynamometry at 12 months
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: University of Texas
name: Randall J Urban, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: Melinda Sheffield-Moore, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Transitional Learning Center
name: Brent Masel, MD
role: PRINCIPAL_INVESTIGATOR
References: