Combining Armodafinil With Neuro-rehabilitation to Improve Neurological Recovery and Reduce Disability Post-Stroke

Use of a Wakefulness-Promoting Agent (Armodafinil) Combined With Neuro-rehabilitation to Improve Neurological Recovery and to Reduce the Incidence of Disability in Patients Who Suffered a Stroke

Armodafinil is an FDA approved medication with wakefulness-promoting properties. It is a relatively safe agent with interesting neurochemical effects on the catecholamine system, producing an improvement in cognitive function, particularly working memory in humans. When combined with intensive task-related training, armodafinil may accelerate motor recovery in chronic stroke patients.

The primary aim of this study is to determine whether administration of armodafinil during subacute post-stroke rehabilitation will augment cortical plasticity and enhance motor recovery. The primary hypothesis suggests that cortical plasticity will be enhanced by armodafinil and, therefore, will induce an improvement in motor function and better performances on measures of motor control.

Study Overview

• Status: Completed
• Conditions: Stroke; Hemiparesis; Cerebrovascular Accident
• Intervention / Treatment: Drug: Armodafinil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • White Plains, New York, United States, 10605
      • The Burke Rehabilitation Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• First clinical stroke, either cerebral infarction or intracerebral hemorrhage
• Severe hemiparesis as measured by a Fugl-Meyer motor scale score of 0-25
• Screening Motricity Index score of 0-83
• Date of stroke onset between 7 to 21 days prior to study inclusion

Exclusion Criteria:

• Age less than 18
• Previous clinical stroke
• Pregnant and/or nursing patients
• Major psychiatric history, including psychosis and history of substance abuse
• Dementia
• Known CNS pathology such as brain tumor
• Significant language dysfunction or severe neglect that hinders comprehension, participation, and barrier to testing
• Seizures
• Left ventricular hypertrophy (LVH)
• Mitral valve prolapse (MVP)
• Severe chronic renal failure or severe hepatic failure
• History or current use of anti-epileptic medications, psychostimulants, or neuroleptics
• Current use of diazepam, phenytoin, propranolol, tricyclic antidepressants, steroidal contraceptives, cyclosporine, or theophylline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Armodafinil; 150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days	Drug: Armodafinil; Other Names: Nuvigil
Placebo Comparator: Placebo; inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days	Drug: Placebo; inactive pill manufactured to mimic Armodafinil 150 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fugl-Meyer Assessment of Sensorimotor Function From Baseline to Day 100	Fugl-Meyer Assessment (FMA) scale is an index to assess the sensorimotor impairment in individuals who have had a stroke.The maximum possible score in Fugl-Meyer scale is 226, which corresponds to full sensory-motor recovery. The Fugl-Meyer Assessment scale is an ordinal scale that has 3 points for each item. A zero score is given for the item if the subject cannot do the task. A score of 1 is given when the task is performed partially and a score of 2 is given when the task is performed fully. However, reflex activity is measured using 2 points only, with a score of 0 or 2 for absence and presence of reflex respectively. The five domains assessed by Fugl-Meyer scale are: Motor function (Maximum score in upper limb = 66;Maximum score in lower limb = 34); Sensory function (Maximum score = 24); Balance (Maximum score = 14); Range of motion of joints (Maximum score = 44); Joint pain (Maximum score = 44)	Baseline to Day 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Functional Independence Measure (FIM) From Baseline to Day 100	The FIM is used by health care practitioners to assess and grade the functional status of a person based on the level of assistance he or she requires. The motor subscale includes:Eating,Grooming,BathingDressing, upper body,Dressing, lower body Toileting Bladder management Bowel management Transfers - bed/chair/wheelchairTransfers - toiletTransfers - bath/showerWalk/wheelchairStairs The cognition subscale includes:Comprehension ExpressionSocial interaction Problem solvingMemory Each item is scored on a 7 point ordinal scale, ranging from a score of 1(worse) to a score of 7(better). The total score for the FIM motor subscale (the sum of motor subscale ) will be a value between 13 and 91.The total score for the FIM cognition subscale (the sum of the individual cognition subscale items) will be a value between 5(worse outcome) & 35(best outcome).The total score for the FIM instrument (the sum of subscale scores) will be a value between 18(worse outcome) & 126 (best outcome)	Day 100
Timed 3-Minute Walk Test From Baseline to Day 100	The 3MWT is a simple measure of the distance a person can walk in three minutes. Rest breaks are allowed if needed. The person is encouraged to walk as fast as they can, safely, for two minutes. Walking aids can be used as needed e.g. for elderly people with a record made of walking aid used.A clear course such as a hallway with cones or similar to mark an approximately 15m "out and back" course[8], stopwatch, pen and paper or a device to record distance walked.	Day 1, Day 100
NIH Stroke Scale (NIHSS)	The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0 Score. Stroke severity 0 No stroke symptoms 1-4 Minor stroke 5-15 Moderate stroke 16-20 Moderate to severe stroke 21-42 Severe stroke	Baseline Day 100
9-Hole Peg Test	9 HOLE PEG TEST; Administered by asking the client to take the pegs from a container, one by one, and place them into the holes on the board, as quickly as possible; Participants must then remove the pegs from the holes, one by one, and replace them back into the container; The board should be placed at the client's midline, with the container holding the pegs oriented towards the hand being tested; Only the hand being evaluated should perform the test; Hand not being evaluated is permitted to hold the edge of the board in order to provide stability; Scores are based on the time taken to complete the test activity, recorded in seconds; Alternative scoring - the number of pegs placed in 50 or 100 seconds can be recorded. In this case, results are expressed as the number of pegs placed per second; Stopwatch should be started from the moment the participant touches the first peg until the moment the last peg hits the container	Baseline & Day 100

Collaborators and Investigators

• Sponsor: Burke Rehabilitation Hospital
• Collaborators: Teva Branded Pharmaceutical Products R&D, Inc.
• Investigators: Principal Investigator: Pasquale Fonzetti, MD, PhD, The Burke Rehabilitation Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: July 2, 2013
• First Submitted That Met QC Criteria: July 8, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): November 4, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: stroke; neuroplasticity; hemiparesis; cerebrovascular accident; CVA; impairment; motor recovery; nuvigil; armodafinil
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Paresis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: BRC-394