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

NCT ID: NCT02114775

Last Updated: 2018-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-12
• Study Completion Date: 2017-11-10

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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Growth Hormone

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

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

Sildenafil

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

Group Type: ACTIVE_COMPARATOR

Sildenafil

Intervention Type: DRUG

50 mg by mouth daily

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Sildenafil

50 mg by mouth daily

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Genotropin; Viagra

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

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Randall J Urban, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Melinda Sheffield-Moore, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Brent Masel, MD

Role: PRINCIPAL_INVESTIGATOR

Transitional Learning Center

Locations

University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

Other Identifiers

13-0324

Identifier Type: -

Identifier Source: org_study_id