Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury. - Full Text View

Sponsors and Collaborators:	University of Texas Southwestern Medical Center Baylor University
Information provided by:	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00766038

Purpose

Growth Hormone (GH) deficiency, defined by insufficient GH response to a variety of stimulating compounds, is found in 20-35% of adults who suffer traumatic brain injuries (TBI) requiring inpatient rehabilitation1. However, there is no accepted gold standard for diagnosing GH deficiency in this population. Further, the major effector molecule of the somatotropic axis, Insulin-Like Growth Factor-1 (IGF-1) has recently been recognized as an important neurotrophic agent. Since most repair and regeneration after TBI occurs within the first few months after injury, absolute or relative deficiencies of GH and IGF-1 in the subacute period after TBI are potentially important factors why some patients fail to make a good functional recovery. The proposed study is a randomized, double-blind, placebo-controlled trial of rhGH, starting at 1 month post TBI, continuing for 6 months.

This study has one primary hypothesis, that treatment with recombinant human Growth Hormone (rhGH) in the subacute period after TBI results in improved functional outcome 6 months after injury. As secondary hypotheses, we will investigate what is the optimal method to diagnose GH deficiency in TBI survivors and study the relationship between GH deficiency and insufficiency and functional recovery.

Condition	Intervention	Phase
Traumatic Brain Injury	Drug: Recombinant human Growth Hormone Drug: Placebo	Phase II

MedlinePlus related topics: Rehabilitation Traumatic Brain Injury

Drug Information available for: Insulin-like growth factor I Mecasermin rinfabate Somatotropin Somatropin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase II, Randomized Controlled Trial of Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury.

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

Treatment with recombinant human Growth Hormone (rhGH) in the subacute period after TBI results in improved functional outcome 6 months after injury, as measured by the Composite Outcome Score of the TBI Clinical Trials Network . [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Treatment with rhGH results in increased IGF-1 levels. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Benefits of rhGH treatment persist up to 1 year after injury [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Low GH response to L-arginine stimulation at baseline is associated with poor functional outcome. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Low IGF-1 levels at baseline are associated with poor functional outcomes. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
rhGH treatment is more effective in patients who have low IGF-1 levels at baseline. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
rhGH treatment is more effective in patients who have low GH response to L-Arginine stimulation at baseline. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
rhGH treatment in during rehabiliation fromTBI is not associated with increased rate of diabetes mellitus, arthralgias, or peripheral edema. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	164
Study Start Date:	September 2008
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment.	Drug: Recombinant human Growth Hormone 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements
2: Placebo Comparator Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding.	Drug: Placebo SC injection daily

Arms

Assigned Interventions

1: Experimental

The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment.

Drug: Recombinant human Growth Hormone

400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements

2: Placebo Comparator

Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding.

Drug: Placebo

SC injection daily

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Non-penetrating TBI
Age 18 - 50 years.
Admission to a North Texas Traumatic Brain Injury Model System-affiliated rehabilitation unit within 8 weeks of injury. Enrollment in TBI-MS database not required.
Randomization within 2 - 10 weeks of injury.
Rancho Los Amigos Rating IV or better at the time of randomization. Should not be at Rancho IV level for more than 4 weeks before randomization.
GH deficiency diagnosed by either of the following two criteria:
1. . Peak GH response to L-arginine stimulation test < 1.4 microg/L; or
2. . Plasma IGF-1 level 1 SD below the expected median for age and body weight.
Availability of caregiver to oversee administration of medications.
Reasonable expectation for completion of outcome measures
Residence inside the United States

Exclusion Criteria:

History of pre-existing neurologic disease (such as epilepsy, brain tumors, meningitis, cerebral palsy, encephalitis, brain abscesses, vascular malformations, cerebrovascular disease, Alzheimer's disease, multiple sclerosis, or HIV-encephalitis)
History of premorbid disabling condition that interfere with outcome assessments
Contraindication to rhGH therapy. (hypersensitivity to rhGH or any of the components of the supplied product, including metacresol, glycerin, or benzyl alcohol)
Penetrating traumatic brain injury
Diabetes mellitus.
Obesity (BMI > 30).
Active infection.
Active malignant disease.
Acute critical illness, heart failure, or acute respiratory failure
Previous hospitalization for TBI > 1 day
Membership in a vulnerable population (prisoner)
Pregnancy. Women of childbearing age will be given a pregnancy test during screening to exclude pregnancy.
Lactating females

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00766038

Locations

United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-9036
Baylor University Medical Center
Dallas, Texas, United States, 75226

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Baylor University

Investigators

Principal Investigator:	Ramon R. Diaz-Arrastia, MD, PhD	University of Texas Southwestern Medical Center
Study Director:	Mary C. Carlile, MD	Baylor University

More Information

Responsible Party:	University of Texas Southwestern Medical Center ( Ramon Diaz-Arrastia, MD, PhD )
Study ID Numbers:	NTTBIMS-GH RCT, NIDRR H133A07002708, Pfizer GA62816O
Study First Received:	September 30, 2008
Last Updated:	September 30, 2008
ClinicalTrials.gov Identifier:	NCT00766038
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:

Mood disorders
Cognitive disorders
Fatigue
Metabolic disorders

Study placed in the following topic categories:

Craniocerebral Trauma
Fatigue
Metabolic Diseases
Wounds and Injuries
Mood Disorders
Disorders of Environmental Origin

Central Nervous System Diseases
Trauma, Nervous System
Metabolic disorder
Brain Diseases
Brain Injuries
Cognition Disorders

Additional relevant MeSH terms:

Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009