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

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

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.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury; Acquired Brain Injury; Coma; Minimally Conscious State; Persistent Vegetative State
• Intervention / Treatment: Drug: Amantadine; Procedure: MRI Tractography Study

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 Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pankaj Bansal, MD; Phone Number: 9055748515; Email: bansalp@hhsc.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Changes	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.	At baseline and ninety days or at time of discharge from hospital if occurs earlier.

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Pankaj E Bansal, MD, Hamilton Health Sciences Corporation; Principal Investigator: Seyed Hosseini, MD, Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 30, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Estimate): December 11, 2015
• Last Update Submitted That Met QC Criteria: December 10, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: traumatic brain injury; mri; tractography; acquired brain injury; abi; coma; amantadine; tbi
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Brain Damage, Chronic; Craniocerebral Trauma; Trauma, Nervous System; Unconsciousness; Consciousness Disorders; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Persistent Vegetative State; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: 0452