SRT5: Predictors of Response in Chronic Stroke

• Sponsor: VA Pittsburgh Healthcare System (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT04283253
• Collaborator: University of Pittsburgh (Other)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will validate a predictive model that uses demographics, functional status, neurophysiology, neuroanatomy, and other potential biomarkers to predict the likelihood of a clinically significant change in impairment at the end of a robot assisted therapy intervention.The study will include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS), and an arm exercise program consisting of robot-assisted exercise combined with functional arm exercise called transition to task training (TTT).

Condition or Disease	Intervention/Treatment	Phase
Stroke; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases	Device: Robot + TTT exercise	N/A

Detailed Description

After informed consent, a baseline neurological exam, medical records review, MRI of the brain, TMS, questionnaires, cognitive testing, robot evaluations, and arm function testing will occur. Baseline testing will occur in the first 4-6 weeks of participation including two separate sessions approximately 1 week a part to examine arm strength, range of motion, and ability to perform functional tasks, with one additional session if needed to verify stability between results. Additionally, one robot evaluation will be completed.

The intervention phase consists of 12 weeks of robot and transition to task arm exercise training (TTT). Interventions will occur approximately 3 times per week for 12 weeks for a total of 36 visits. Additional time and visits will be allowed with visits occurring 4 times per week or up to 6 additional weeks (not to exceed 18 weeks) if scheduling conflicts arise. The intervention sessions will be one hour in duration.

During the hour-long intervention, 45 minutes of robotic intervention will be followed by 15 minutes of TTT. The training will be sequential with 12 sessions focused on the wrist, followed by 12 sessions on the shoulder-elbow and the final 12 sessions alternating between the wrist and elbow-shoulder.

After the final training session, subjects will return after a 12 week retention period. At various time points during and after the intervention phase there will be additional arm function testing, robot evaluations, questionnaires, MRI and TMS sessions for re-assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: One-arm, multiple baseline sequential, cohort studyOne-arm, multiple baseline sequential, cohort study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neurophysiological and Kinematic Predictors of Response in Chronic Stroke
• Actual Study Start Date: Oct 22, 2019
• Actual Primary Completion Date: Mar 31, 2020
• Actual Study Completion Date: Mar 31, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Robot + TTT Exercise All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises.

Device: Robot + TTT exercise; The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.

Outcome Measures

Primary Outcome Measures

1. A Change in the Fugl-Meyer Upper Extremity Assessment Score [Immediately following the 12-week intervention]

   The Fugl-Meyer is one of the primary outcome measures assessing change in arm use from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a stroke-specific measure of impairment of the upper extremity that has been shown to be valid and reliable with high inter-rater and test-retest reliability. It provides a direct-observational assessment of volitional movement and motor impairment related to reflexes, sensation, and abnormal synergies. Each item on the FM is rated on a three-point ordinal scale (0 = cannot perform, 1 = performs partially, 2 = performs fully). The scale ranges from 0-66 with higher scores representing less motor impairment.

Other Outcome Measures

1. A Change in Motor Evoked Potential During Transcranial Magnetic Stimulation of the Motor Cortex [Immediately following the 12-week intervention]

   TMS stimulation of the motor cortex will be performed using MagStim 200 Magnetic Stimulators (MagStim Ltd., Wales, UK) to assess change in the motor evoked potential (MEP) of the arm muscles.

2. A Change in Brain Connections Assessed Via MRI of the Brain [Immediately following the 12-week intervention]

   A detailed analysis of the MRI data will examine individual interregional connections to determine whether any of them are more sensitive to the intervention than others.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinically defined, unilateral, hemiparetic stroke with radiologic exclusion of other possible diagnosis

• Stroke onset at least 6 months before enrollment

• Present with Mild/Moderate to Severe arm dysfunction (based on Fugl-Meyer scores of 10 to 45)

• Be medically stable to participate in the study

• Be English speaking

Exclusion Criteria:

• Unable to give informed consent

• Have a serious complicating medical illness that would preclude participation.

• Contractures or orthopedic problems limiting range of joint motion in the potential study arm

• Visual loss such that the subject would not be able to see the test patterns on the robot computer monitor

• Botulinum toxin to study arm within four months of study enrollment or if received during the study period

• Unable to comply with requirements of the study

• Participants with a history of a seizure will not be precluded from the study, but will not be enrolled in the TMS portions

• Participants with electromagnetic exclusions (metal implants in the cranium, implanted electronic devices etc.) will not be precluded from the study but will be excluded from the MRI and TMS portions

• Have a serious complicating medical illness that would preclude participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• VA Pittsburgh Healthcare System
• University of Pittsburgh

Investigators

• Principal Investigator: George Wittenberg, PhD, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 21, 2021
• Informed Consent Form - Feb 10, 2020

More Information

Publications

• Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017 Mar 7;135(10):e146-e603. doi: 10.1161/CIR.0000000000000485. Epub 2017 Jan 25. Review. Erratum in: Circulation. 2017 Mar 7;135(10 ):e646. Circulation. 2017 Sep 5;136(10 ):e196.
• Connell LA, Smith MC, Byblow WD, Stinear CM. Implementing biomarkers to predict motor recovery after stroke. NeuroRehabilitation. 2018;43(1):41-50. doi: 10.3233/NRE-172395. Review.
• Gauthier LV, Taub E, Mark VW, Perkins C, Uswatte G. Improvement after constraint-induced movement therapy is independent of infarct location in chronic stroke patients. Stroke. 2009 Jul;40(7):2468-72. doi: 10.1161/STROKEAHA.109.548347. Epub 2009 May 21.
• Lang CE, Bland MD, Bailey RR, Schaefer SY, Birkenmeier RL. Assessment of upper extremity impairment, function, and activity after stroke: foundations for clinical decision making. J Hand Ther. 2013 Apr-Jun;26(2):104-14;quiz 115. doi: 10.1016/j.jht.2012.06.005. Epub 2012 Sep 10. Review.
• Mehrholz J, Pohl M, Platz T, Kugler J, Elsner B. Electromechanical and robot-assisted arm training for improving activities of daily living, arm function, and arm muscle strength after stroke. Cochrane Database Syst Rev. 2018 Sep 3;9:CD006876. doi: 10.1002/14651858.CD006876.pub5. Review.
• Stinear CM, Byblow WD, Ackerley SJ, Barber PA, Smith MC. Predicting Recovery Potential for Individual Stroke Patients Increases Rehabilitation Efficiency. Stroke. 2017 Apr;48(4):1011-1019. doi: 10.1161/STROKEAHA.116.015790. Epub 2017 Mar 9.

• Responsible Party: VA Pittsburgh Healthcare System
• ClinicalTrials.gov Identifier: NCT04283253
• Other Study ID Numbers: Pro00003161
• First Posted: Feb 25, 2020
• Last Update Posted: Mar 3, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Stroke; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases; Cardiovascular Diseases

Study Results

Participant Flow

Arm/Group Title	Robot + TTT Exercise
Arm/Group Description	All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises. Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Robot + TTT Exercise
Arm/Group Description	All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises. Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	1 100%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	A Change in the Fugl-Meyer Upper Extremity Assessment Score
Description	The Fugl-Meyer is one of the primary outcome measures assessing change in arm use from baseline testing to mid-training after visits 12 and 24, and post-training after visit 36 and the 12 week retention period. It is a stroke-specific measure of impairment of the upper extremity that has been shown to be valid and reliable with high inter-rater and test-retest reliability. It provides a direct-observational assessment of volitional movement and motor impairment related to reflexes, sensation, and abnormal synergies. Each item on the FM is rated on a three-point ordinal scale (0 = cannot perform, 1 = performs partially, 2 = performs fully). The scale ranges from 0-66 with higher scores representing less motor impairment.
Time Frame	Immediately following the 12-week intervention

Outcome Measure Data

Analysis Population Description

Only one subject was enrolled and data collection was incomplete due to the Covid-19 pandemic. The evaluations following the 12-week intervention were not performed.

Arm/Group Title	Robot + TTT Exercise
Arm/Group Description	All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises. Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
Measure Participants	1
Baseline One	11
Baseline Two	12
After Visit 12	13
After Visit 24	14

2. Other Pre-specified Outcome

Title	A Change in Motor Evoked Potential During Transcranial Magnetic Stimulation of the Motor Cortex
Description	TMS stimulation of the motor cortex will be performed using MagStim 200 Magnetic Stimulators (MagStim Ltd., Wales, UK) to assess change in the motor evoked potential (MEP) of the arm muscles.
Time Frame	Immediately following the 12-week intervention

Outcome Measure Data

Analysis Population Description

Only one subject was enrolled and data collection was incomplete due to the Covid-19 pandemic. The evaluations (including TMS) following the 12-week intervention were not performed.

Arm/Group Title	Robot + TTT Exercise
Arm/Group Description	All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises. Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
Measure Participants	0

3. Other Pre-specified Outcome

Title	A Change in Brain Connections Assessed Via MRI of the Brain
Description	A detailed analysis of the MRI data will examine individual interregional connections to determine whether any of them are more sensitive to the intervention than others.
Time Frame	Immediately following the 12-week intervention

Outcome Measure Data

Analysis Population Description

MRI was not collected as the one enrolled subject did not pass the MRI safety screening.

Arm/Group Title	Robot + TTT Exercise
Arm/Group Description	All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises. Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
Measure Participants	0

Adverse Events

Time Frame	5 months
Arm/Group Title	Robot + TTT Exercise
Arm/Group Description	All participants will be enrolled in this group to receive the same 60 minute study intervention consisting of wrist and shoulder-elbow robot training and TTT arm exercises. Robot + TTT exercise: The intervention will be completed 36 visits approximately 3x/week for 12-18 weeks. The training progression will be sequential with 12 visits completed on the wrist robot, followed by 12 visits on the shoulder-elbow robot and completing with 12 visits alternating sessions on the wrist and shoulder-elbow robot. Participants will perform robot training for 45 minutes with each robot followed by 15 minutes of TTT practice to complete their 60 minute intervention session.
All Cause Mortality
	Robot + TTT Exercise
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Robot + TTT Exercise
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Robot + TTT Exercise
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.