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

The University of Texas System (UT)

Status and phase: Completed; Phase 1

Conditions: Traumatic Brain Injury

Treatments: Drug: Placebo; Drug: Sildenafil; Drug: Growth Hormone

Study type: Interventional

Funder types: Other

Identifiers

NCT02114775

13-0324

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

34 participants in 2 patient groups

Recombinant Growth Hormone

Active Comparator group

Description:

Double blind placebo/Genotropin cross over design for 6 months with cross over at 3 months. Then open label Genotropin from month 6 - 12.

Treatment:

Drug: Placebo

Drug: Growth Hormone

Sildenafil

Active Comparator group

Description:

Double blinded placebo/Sildenafil crossover design for 6 months with crossover at month 3. Then open label Sildenafil from months 6-12.

Treatment:

Drug: Placebo

Drug: Sildenafil