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

Sponsor

Hamilton Health Sciences Corporation (Other)

Overall Status

Unknown status

CT.gov ID

NCT02566720

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acquired Brain Injury Coma Persistent Vegetative State Minimally Conscious State Traumatic Brain Injury	Drug: Amantadine Procedure: MRI Tractography Study	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Official Title:

Mechanism of Amantadine and Functional Improvement Following Acquired Brain Injury as Measured by MRI Tractography; A Pilot Study

Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Treatment and MRI scanning 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.	Drug: Amantadine Participants will initially receive amantadine at the starting dose of 50mg twice daily either by mouth or feeding tube. The dosage will increase every week by 50mg twice daily (100mg total dose increase) up to the target dose of 200mg twice daily. These are the usual doses and rate of increase that are offered to patients with brain injury. Other Names: amantadine hydrochloride Procedure: MRI Tractography Study Participants will initially receive a baseline MRI Tractography scan. The size of RAS fiber tracts will be measured prior to initiating treatment and near the time of discharge from the rehabilitation hospital or at approximately ninety-days.

Arm

Intervention/Treatment

Other: Treatment and MRI scanning

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.

Drug: Amantadine

Participants will initially receive amantadine at the starting dose of 50mg twice daily either by mouth or feeding tube. The dosage will increase every week by 50mg twice daily (100mg total dose increase) up to the target dose of 200mg twice daily. These are the usual doses and rate of increase that are offered to patients with brain injury.

Other Names:

amantadine hydrochloride

Procedure: MRI Tractography Study

Participants will initially receive a baseline MRI Tractography scan. The size of RAS fiber tracts will be measured prior to initiating treatment and near the time of discharge from the rehabilitation hospital or at approximately ninety-days.

Outcome Measures

Primary Outcome Measures

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

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hamilton Health Sciences	Hamilton	Ontario	Canada

Sponsors and Collaborators

Hamilton Health Sciences Corporation

Investigators

Principal Investigator: Pankaj E Bansal, MD, Hamilton Health Sciences Corporation
Principal Investigator: Seyed Hosseini, MD, Hamilton Health Sciences Corporation