Amantadine and Functional Improvement Following ABI Measured by MRI Tractography; A Pilot Study

Not Applicable

• Conditions: Coma; Persistent Vegetative State; Acquired Brain Injury; Traumatic Brain Injury; Minimally Conscious State
• Interventions: Drug: Amantadine; Procedure: MRI Tractography Study

• Registration Number: NCT02566720
• Lead Sponsor: Hamilton Health Sciences Corporation

Brief Summary

This is a pilot study. The objective is to further understand the mechanism by which amantadine improves function in patients with persistent vegetative state and minimally conscious state. Specifically, the investigators will measure the size of the nerve fibers that mediate arousal (reticular activating system, or RAS) pre and post treatment on MRI tractography. MRI findings will be correlated with the Disability Rating Scale (DRS) score. The information gathered from this study will be used to formulate a larger clinical trial.

Detailed Description

Primary Aim:

To determine the size of the RAS tracts as measured by MRI tractography. Specifically, the investigators will be measuring the fiber tracts that project through the posterior thalamus. The RAS is involved in mediating arousal and consciousness. The size of fiber tracts will be measured prior to initiating treatment and near the time of discharge from the rehabilitation hospital or at approximately ninety-days. It is hypothesized that treatment will result in an increase in the size of these fiber tracts.

As a pilot study, the investigators will be determining the feasibility of recruiting and retaining patients in this type of study. This will allow the clarification and understanding of the technical standards for MRI tractography related to the assessment of the reticular activating system.

Secondary Aim:

To determine and monitor changes in function following acquired brain injury as measured by the Disability Rating Scale (DRS) score. The DRS score will be obtained prior to initiating treatment and at termination of the study. It is hypothesized that treatment with amantadine in addition to standard medical treatment, will be associated with an improvement in function.

Study Timeline

• Study First Submitted: 2015-09-23
• Study First Submitted QC: 2015-09-30
• Study First Posted: 2015-10-02
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-10
• Last Update Posted: 2015-12-11
• Study Start: 2016-01
• Primary Completion: 2016-12
• Study Completion: 2017-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Age 18 years - 65 years
• Nonpenetrating acquired brain injury (ABI)
• Persistent vegetative or minimally conscious state (as indicated by DRS score greater than 11)
• Consent from substitute decision maker

Exclusion Criteria

• Contraindication to MRI (such as metal in the body, pacemaker, implanted nerve stimulator)
• Anticipated neurosurgical intervention
• Medical instability including uncontrolled hypertension, fever, or infection
• Seizure disorder prior to acquired brain injury or uncontrolled seizures subsequent to acquired brain injury
• Parkinson's disease
• History of heart failure or pre-existing peripheral oedema
• History of eczematoid dermatitis
• History of angle-closure glaucoma
• History of neuroleptic malignant syndrome
• Current treatment with Amantadine
• Impairment related to other neurologic disease other than ABI
• Allergy to Amantadine
• Pregnancy or lactation
• Impairment of renal function (creatinine clearance less than 60ml/min)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment and MRI scanning	MRI Tractography Study	After informed consent has been obtained, the subjects will be examined by a physician and assigned a Disability Ratings Scale (DRS) score. Subjects will undergo MRI tractography study, which does not require the administration of contrast. All participants will receive oral amantadine at escalating doses to ensure tolerance (50mg twice daily for 7 days, then 100mg twice daily for 1 week, then 150mg twice daily, then 200mg twice daily). The usual length of stay on the inpatient brain injury program is ninety days. The MRI tractography study and DRS score will be repeated near the time of discharge or ninety days from enrollment.
Treatment and MRI scanning	Amantadine	After informed consent has been obtained, the subjects will be examined by a physician and assigned a Disability Ratings Scale (DRS) score. Subjects will undergo MRI tractography study, which does not require the administration of contrast. All participants will receive oral amantadine at escalating doses to ensure tolerance (50mg twice daily for 7 days, then 100mg twice daily for 1 week, then 150mg twice daily, then 200mg twice daily). The usual length of stay on the inpatient brain injury program is ninety days. The MRI tractography study and DRS score will be repeated near the time of discharge or ninety days from enrollment.

Primary Outcome Measures

Name	Time	Method
Radiographic Changes	At baseline and ninety days or at time of discharge from hospital if occurs earlier.	MRI Tractography will be performed to measure the size the of reticular activating system fiber tracts. Specifically, the tracts that project through the posterior thalamus.

Secondary Outcome Measures

Name	Time	Method
Functional Improvement	At ninety days or at time of discharge from hospital if occurs earlier.	Disability Rating Scale Score (at enrolment and at completion of the study).

Trial Locations

Locations (1)

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada