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

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02566720
• Other study ID #: 0452
• Status: Not yet recruiting
• Phase: N/A
• First received: September 23, 2015
• Last updated: December 10, 2015
• Start date: January 2016
• Est. completion date: June 2017

Study information

• Verified date: December 2015
• Source: Hamilton Health Sciences Corporation
• Contact: Pankaj Bansal, MD
• Phone: 9055748515
• Email: bansalp[@]hhsc.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: June 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Acquired Brain Injury
• Brain Injuries
• Coma
• Minimally Conscious State
• Persistent Vegetative State
• Traumatic Brain Injury

Intervention

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.

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.

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No