Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury.

NCT00766038 | Completed Phase 2 Results DMC

• 3 other identifiers: NTTBIMS-GH RCTNIDRR H133A07002708Pfizer GA62816O
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Traumatic Brain Injury

Keywords

Mood disorders; Cognitive disorders; Fatigue; Metabolic disorders

Outcome Measures

Primary Outcomes (1)

• Functional Outcome 6 Months After Injury, as Measured by the Processing Speed Index

  Processing Speed Index ages standardized score. In this scale, higher scores represent better functioning, lower scores represent poorer function. 100 = mean of a normative population. 110 = 1 standard deviation above normal; 90 = 1 standard deviation below normal 120 = 2 standard deviations above normal; 80 = 2 standard deviations below normal

  6 months

Secondary Outcomes (5)

• IGF-1 Levels.

  4 years

• Processing Speed Index 1 Year After Injury

  1 year

• GH Response to L-arginine Stimulation at Baseline

  1 day

• IGF-1 Levels

  Baseline

• Rates of Diabetes Mellitus, Arthralgias, or Peripheral Edema.

  4 years

Study Arms (2)

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

2

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Recombinant human Growth Hormone DRUG

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

Also known as: Somatotropin, Genotropin(R), HGH

1

Placebo DRUG

SC injection daily

2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Peak GH response to L-arginine stimulation test \< 1.4 microg/L; or
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Baylor Health Care System: collaborator

Study Sites (3)

Center for NeuroSkills

Bakersfield, California, United States

Location

Baylor University Medical Center

Dallas, Texas, 75226, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9036, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Mood Disorders; Cognitive Dysfunction; Fatigue; Metabolic Diseases

Interventions

Growth Hormone

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Mental Disorders; Cognition Disorders; Neurocognitive Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Ramon Diaz-Arrastia
• Organization: University of Pennsylvania

Ramon.Diaz-Arrastia@uphs.upenn.edu

215-662-9732

Study Officials

• Ramon R. Diaz-Arrastia, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Randi Dubiel, MD

  Baylor Health Care System

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: September 30, 2008
• First Posted: October 3, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: December 1, 2013
• Last Updated: November 18, 2019
• Results First Posted: November 18, 2019

Record last verified: 2019-11

Locations

US (3)