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

Growth Hormone or Sildenafil as Therapies for Fatigue in MTBI

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Growth Hormone; Drug: Placebo; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Placebo; Placebo either injected (GH group) or orally (sildenafil group) daily for three months during crossover phase of the study; Drug: Sildenafil; 50 mg by mouth daily; Other Names: Viagra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance fatigue as measured by using hand grip dynamometry at baseline	Hand grip exercises will be used to measure performance fatigue at baseline	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	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	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	12 months
Performance fatigue as measured by using leg dynamometry at baseline	Leg exercises will be used to measure performance fatigue at baseline	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.	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.	6 months
Performance fatigue as measured by using leg dynamometry at 12 months	Leg exercises will be used to measure performance fatigue after 12 months of study	12 months

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Investigators: Principal Investigator: Melinda Sheffield-Moore, PhD, University of Texas; Principal Investigator: Brent Masel, MD, Transitional Learning Center

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2014
• Primary Completion (Actual): November 10, 2017
• Study Completion (Actual): November 10, 2017

Study Registration Dates

• First Submitted: January 31, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimate): April 15, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2018
• Last Update Submitted That Met QC Criteria: February 1, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: fatigue; sildenafil; neurology; growth hormone; mild traumatic brain injury
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Fatigue; Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Hormones; Sildenafil Citrate
• Other Study ID Numbers: 13-0324