The Effect of Single Dose D-Cycloserine on Cognitive Outcome in Moderate Traumatic Brain Injury (TBI) Patients

Study Overview
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Brief Summary
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In this study of patients with moderate traumatic brain injury with frontal brain contusions patients will be randomized to treatment with a single dose of either D-cycloserine or placebo given 48-72 hours after injury. Patients will undergo intensive neurocognitive testing at 3 and 6 months after injury to assess whether treatment with a single dose of D-cycloserine improves cognitive outcome after moderate brain injury.

Official Title
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The Effect of Single Dose D-Cycloserine on Cognitive Outcome in Moderate TBI Patients

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Drug: D-cycloserine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: TBI diagnosed by history and/or clinical examination with presenting GCS between 9 -13 Age between 18 and 55 years Frontal cerebral contusion(s) located in the frontal cortex and/or traumatic subarachnoid hemorrhage on initial CT scan Prior to randomization, patient is able to swallow an orally administered tablet or has a nasogastric tube in place per medical indication Informed consent will be obtained in those patients who have regained full cognition and judgment following their injury and are fully capable of understanding the study protocol, its risks and potential benefits, and of giving informed consent for participation in the study. In any patient that has not regained full cognition and judgment, only a temporary legal guardian (apotropos) appointed by an authorized judge that has been given a full explanation of the study protocol, its risks and potential benefits will be authorized to give informed consent for participation in the study. Exclusion Criteria: Penetrating brain injury Any traumatic intracranial lesion requiring neurosurgical intervention prior to time of randomization Other severe systemic injuries leading to severe hypotension, hemodynamic instability following initial resuscitation (SBP < 90 mmHg), severe hypoxia. Intubation lasting > 12 hours prior to randomization Suspected or confirmed pregnancy or lactating women Any spinal cord injury Known or CT scan evidence of previous major cerebral damage Any severe concomitant condition (malignancy, renal, hepatic, or major psychiatric disorder) Known treatment with another investigational drug within 30 days of injury Known contraindication to enteral administration of drug prior to randomization (GI bleed, ileus, severe abdominal injury, etc.) Known contraindication to placement of a nasogastric tube in patients unable to swallow an orally administered tablet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D- Cycloserine<br> | Drug: D-cycloserine<br>* single dose of D-cycloserine given 48-72 hours after moderate traumatic brain injury<br>* Other names: seromycin;|
| Placebo Comparator: sugar pill<br> | Drug: placebo<br>* A sugar pill will be given to those patients randomized to the control group at 48-72 hours after moderate brain injury<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A battery of neuropsychological tests at 3 and 6 months post-injury | Symbol Digit Modalities Test (Smith 1973) Trail Making Test (TMT) (Reitan, Hom et al. 1988) Digit Span (DS) from the WAIS-III Rey Auditory Verbal Learning Test (RAVLT) (Rey 1955; Lezak 2004) Wisconsin Card Sorting Test (WCST) (Psychological Assessment Resources. Computerised Wisconsin Card Sort Task Version 4 (WCST). Psychological Assessment Resources; 2003). Test of Variables of Attention (TOVA) (Test of Variables of Attention: Clinical Manual. Los Alamitos: The TOVA Company). Behavioral Assessment of the Dysexecutive Syndrome (BADS) (Erez, Rothschild et al. 2009) | 3 and 6 months post-injury | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glasgow Outcome Score - Extended (GOS-E) |  | 3 and 6 months post injury | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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moderate traumatic brain injury, brain contusion