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

Traumatic Brain Injury Clinical Trial

Official title:

Growth Hormone or Sildenafil as Therapies for Fatigue in MTBI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02114775
• Other study ID #: 13-0324
• Status: Completed
• Phase: Phase 1
• First received: January 31, 2014
• Last updated: February 1, 2018
• Start date: December 12, 2014
• Est. completion date: November 10, 2017

Study information

• Verified date: February 2018
• Source: The University of Texas Medical Branch, Galveston
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: November 10, 2017
• Est. primary completion date: November 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Concussion
• Brain Injuries
• Brain Injuries, Traumatic
• Fatigue
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

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
• Sildenafil
50 mg by mouth daily
• Placebo
Placebo either injected (GH group) or orally (sildenafil group) daily for three months during crossover phase of the study

Locations

Country	Name	City	State
United States	University of Texas Medical Branch	Galveston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Medical Branch, Galveston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Performance fatigue as measured by using hand grip dynamometry at baseline	Hand grip exercises will be used to measure performance fatigue at baseline	baseline
Primary	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
Primary	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
Primary	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
Primary	Performance fatigue as measured by using leg dynamometry at baseline	Leg exercises will be used to measure performance fatigue at baseline	baseline
Primary	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
Primary	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
Primary	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