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

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

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.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: D-cycloserine; Drug: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Ramat Gan, Israel
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. TBI diagnosed by history and/or clinical examination with presenting GCS between 9 -13
2. Age between 18 and 55 years
3. Frontal cerebral contusion(s) located in the frontal cortex and/or traumatic subarachnoid hemorrhage on initial CT scan
4. Prior to randomization, patient is able to swallow an orally administered tablet or has a nasogastric tube in place per medical indication
5. 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:

1. Penetrating brain injury
2. Any traumatic intracranial lesion requiring neurosurgical intervention prior to time of randomization
3. Other severe systemic injuries leading to severe hypotension, hemodynamic instability following initial resuscitation (SBP < 90 mmHg), severe hypoxia.
4. Intubation lasting > 12 hours prior to randomization
5. Suspected or confirmed pregnancy or lactating women
6. Any spinal cord injury
7. Known or CT scan evidence of previous major cerebral damage
8. Any severe concomitant condition (malignancy, renal, hepatic, or major psychiatric disorder)
9. Known treatment with another investigational drug within 30 days of injury
10. Known contraindication to enteral administration of drug prior to randomization (GI bleed, ileus, severe abdominal injury, etc.)
11. Known contraindication to placement of a nasogastric tube in patients unable to swallow an orally administered tablet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Investigators: Principal Investigator: Guy Rosenthal, MD, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): May 1, 2014
• Study Completion (Anticipated): May 1, 2014

Study Registration Dates

• First Submitted: April 27, 2011
• First Submitted That Met QC Criteria: April 27, 2011
• First Posted (Estimate): April 28, 2011

Study Record Updates

• Last Update Posted (Estimate): April 28, 2011
• Last Update Submitted That Met QC Criteria: April 27, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: moderate traumatic brain injury; brain contusion
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: 0046-10-HMO