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

Sponsor

The University of Texas Medical Branch, Galveston (Other)

Overall Status

Completed

CT.gov ID

NCT02114775

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury	Drug: Growth Hormone Drug: Sildenafil Drug: Placebo	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Diagnostic

Official Title:

Growth Hormone or Sildenafil as Therapies for Fatigue in MTBI

Actual Study Start Date :

Dec 12, 2014

Actual Primary Completion Date :

Nov 10, 2017

Actual Study Completion Date :

Nov 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Recombinant Growth Hormone Double blind placebo/Genotropin cross over design for 6 months with cross over at 3 months. Then open label Genotropin from month 6 - 12.	Drug: Growth Hormone 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 Other Names: Genotropin Drug: Placebo Placebo either injected (GH group) or orally (sildenafil group) daily for three months during crossover phase of the study
Active Comparator: Sildenafil Double blinded placebo/Sildenafil crossover design for 6 months with crossover at month 3. Then open label Sildenafil from months 6-12.	Drug: Sildenafil 50 mg by mouth daily Other Names: Viagra Drug: Placebo Placebo either injected (GH group) or orally (sildenafil group) daily for three months during crossover phase of the study

Arm

Intervention/Treatment

Active Comparator: Recombinant Growth Hormone

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

Drug: Growth Hormone

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

Other Names:

Genotropin

Drug: Placebo

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

Active Comparator: Sildenafil

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

Drug: Sildenafil

50 mg by mouth daily

Other Names:

Viagra

Drug: Placebo

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

Outcome Measures

Primary Outcome Measures

Performance fatigue as measured by using hand grip dynamometry at baseline [baseline]
Hand grip exercises will be used to measure performance fatigue at baseline
Performance fatigue as measured by using hand grip dynamometry at 3 months [3 months]
Hand grip exercises will be used to measure performance fatigue after 3 months of study intervention
Performance fatigue as measured by using hand grip dynamometry at 6 months [6 months]
Hand grip exercises will be used to measure performance fatigue after 6 months of study intervention
Performance fatigue as measured by using hand grip dynamometry at 12 months [12 months]
Hand grip exercises will be used to measure performance fatigue after 12 months of study intervention
Performance fatigue as measured by using leg dynamometry at baseline [baseline]
Leg exercises will be used to measure performance fatigue at baseline
Performance fatigue as measured by using leg dynamometry at 3 months [3 months]
Leg exercises will be used to measure performance fatigue after 3 months of study intervention.
Performance fatigue as measured by using leg dynamometry at 6 months [6 months]
Leg exercises will be used to measure performance fatigue after 6 months of study intervention.
Performance fatigue as measured by using leg dynamometry at 12 months [12 months]
Leg exercises will be used to measure performance fatigue after 12 months of study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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)

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.