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

• Sponsor: Burke Rehabilitation Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01896128
• Collaborator: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Enrollment: 19
• Location: 1
• Arms: 2
• Duration (Months): 90
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Cerebrovascular Accident; Hemiparesis	Drug: Armodafinil; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Fugl-Meyer Assessment of Sensorimotor Function From Baseline to Day 100 [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)

Secondary Outcome Measures

1. Change in Functional Independence Measure (FIM) From Baseline to Day 100 [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)

2. Timed 3-Minute Walk Test From Baseline to Day 100 [Day 1, 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.

3. NIH Stroke Scale (NIHSS) [Baseline Day 100]

   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

4. 9-Hole Peg Test [Baseline & Day 100]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Burke Rehabilitation Hospital	White Plains	New York	United States	10605

Sponsors and Collaborators

• Burke Rehabilitation Hospital
• Teva Branded Pharmaceutical Products R&D, Inc.

Investigators

• Principal Investigator: Pasquale Fonzetti, MD, PhD, The Burke Rehabilitation Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pasquale Fonzetti, MD, PhD, Associate Director, Memory Evaluation and Treatment Service, Burke Rehabilitation Hospital
• ClinicalTrials.gov Identifier: NCT01896128
• Other Study ID Numbers: BRC-394
• First Posted: Jul 11, 2013
• Last Update Posted: Nov 4, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by Pasquale Fonzetti, MD, PhD, Associate Director, Memory Evaluation and Treatment Service, Burke Rehabilitation Hospital: stroke; CVA; cerebrovascular accident; hemiparesis; impairment; motor recovery; neuroplasticity; nuvigil; armodafinil
• Additional relevant MeSH terms: Stroke; Paresis; Modafinil

Study Results

Participant Flow

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
Period Title: Overall Study
STARTED	8	11
COMPLETED	5	8
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Armodafinil	Placebo	Total
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet	Total of all reporting groups
Overall Participants	8	11	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 75%	5 45.5%	11 57.9%
>=65 years	2 25%	6 54.5%	8 42.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.4 (12.4)	67.5 (9.5)	66.45 (10.95)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	6 54.5%	9 47.4%
Male	5 62.5%	5 45.5%	10 52.6%
Region of Enrollment (participants) [Number]
United States	8 100%	11 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Change in Fugl-Meyer Assessment of Sensorimotor Function From Baseline to Day 100
Description	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)
Time Frame	Baseline to Day 100

Outcome Measure Data

Analysis Population Description

data available for participants who completed the study

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
Measure Participants	5	8
Baseline	14.8 (8.6)	12.8 (7.0)
Day100	39.7 (15.0)	37.8 (20.9)

2. Secondary Outcome

Title	Change in Functional Independence Measure (FIM) From Baseline to Day 100
Description	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)
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
Measure Participants	8	11
Baseline	55.5 (17.8)	52.4 (14.5)
Day100	89.2 (21.7)	90.9 (17.4)

3. Secondary Outcome

Title	Timed 3-Minute Walk Test From Baseline to Day 100
Description	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.
Time Frame	Day 1, Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
Measure Participants	8	11
Baseline	49.4 (43.5)	152.5 (89.2)
Day100	152.5 (89.2)	103.3 (73.8)

4. Secondary Outcome

Title	NIH Stroke Scale (NIHSS)
Description	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
Time Frame	Baseline Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
Measure Participants	8	11
Baseline	11.9 (3.9)	13.4 (3.3)
Day100	6.7 (2.5)	7.3 (2.7)

5. Secondary Outcome

Title	9-Hole Peg Test
Description	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
Time Frame	Baseline & Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Armodafinil	Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil	inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
Measure Participants	8	11
Baseline	34.0 (8.8)	34.2 (9.5)
Day100	27.3 (6.7)	29.7 (6.1)

Adverse Events

Time Frame	100 days
Arm/Group Title	Armodafinil		Placebo
Arm/Group Description	150 mg armodafinil administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Armodafinil		inactive agent administered 2 hours prior to start of therapeutic regimen for 10 consecutive days Placebo: inactive pill manufactured to mimic Armodafinil 150 mg tablet
All Cause Mortality
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/11 (0%)
Serious Adverse Events
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Armodafinil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/11 (0%)
Nervous system disorders
Nervesousness	1/8 (12.5%)	1	0/11 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.