Clinical trial NCT02566720: Amantadine and Functional Improvement Following ABI Measured by MRI Tractography; A Pilot Study
Official title: Mechanism of Amantadine and Functional Improvement Following Acquired Brain Injury as Measured by MRI Tractography; A Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acquired Brain Injury
Coma
Persistent Vegetative State
Minimally Conscious State
Traumatic Brain Injury
Keywords: amantadine
tractography
mri
coma
abi
tbi
traumatic brain injury
acquired brain injury
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
First posted: 2015-10-02
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Radiographic Changes
timeFrame: At baseline and ninety days or at time of discharge from hospital if occurs earlier.
Secondary outcomes:
measure: Functional Improvement
timeFrame: At ninety days or at time of discharge from hospital if occurs earlier.
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
Study officials:
affiliation: Hamilton Health Sciences Corporation
name: Pankaj E Bansal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamilton Health Sciences Corporation
name: Seyed Hosseini, MD
role: PRINCIPAL_INVESTIGATOR
References: