Evaluating Neural Adaptation After Tendon Transfer and Task-based Training in SCI
Phase: NA
Conditions: Spinal Cord Injury
Sponsor: VA Office of Research and Development

Neural adaptation after tendon transfer and training in tetraplegia. 
 
ID number: N1772-P 
NCT number: NCT02768103 
IRB approval: March 31, 2019 
 
 

 
 
Purpose 
The purpose of the study is to improve upper limb function in people who have suffered injuries to their cervical 
spinal cord and have lost hand function. Many individuals with tetraplegia choose to undergo surgery, such as 
muscle-tendon transfers that restore function to their paralyzed upper limbs. In this study we will compare their 
ability to produce pinch force between the thumb and index finger before and after participating in a home 
exercise program. The exercises are designed to improve the strength and performance of the transferred 
muscle and also the muscles that are important to stabilize proximal joints. 
 
The investigators anticipate the study will inform new postoperative treatment protocols designed to re-educate 
the transferred muscle in its new functional role. The objective is to determine if training to improve muscle 
strength and coordination will improve the ability to increase pinch strength after tendon transfer to restore 
pinch strength. Restoration of upper extremity function is rated among the highest priorities for individuals with 
tetraplegia. Use of the upper extremity is critical to functional independence, quality of life, ability to participate 
in society, and reduced burden of care. 
 
 
Study Procedures 
Recruitment and screening: We will invite individuals to participate if they have a SCI resulting in tetraplegia 
with a previous tendon transfer surgery to restore their ability to pinch and grasp. Individuals with tetraplegia 
will be recruited from the Upper Extremity Clinics for Spinal Cord Injury at the VA Palo Alto Health Care 
System, Stanford University Hospital Clinics, and Valley Medical Center in San Jose, CA. A hand surgeon and 
the PI will attend all of the clinics. A letter may be sent to individuals who have expressed interest in previous 
studies to be contacted for participation in any new studies.  
 
Participants will be scheduled for 1 to 2 test sessions in the Laboratory for Upper  
Extremity Research in the SCI Center (UE Lab). In the first session a set of measurements will be taken for 
baseline data of strength, muscle activation, and ability to perform functional pinch tasks. An fMRI study will be 
included in the first session. Each participant with tendon transfer procedures will be given a set of exercise 
equipment to take home. The equipment will include a set of weights for resistance exercise (i.e. lifting 
weights), a digital pinch meter for biofeedback of the pinch force, a table-top device that is used to provide 
target locations the participants reach for and to practice pinch (using variable resistance pinch pins) in 
locations that simulate the actual functional pinch tasks, and a task board with tasks that require pinch strength 
(ex: key, atm card, zipper).  
 
The participants will get verbal and written instructions about how to use the equipment and a log-book to 
record their practice sessions. They will be instructed to practice the exercises for 10 weeks. A second 
appointment in the UE Lab will be scheduled to measure any changes in pinch function after the exercise 
program. A set of measurements that are identical to the baseline data set will be obtained, including the fMRI 
study.  
 
Home Exercise Training Program: Participants will be instructed to use resistance exercises to strengthen 
elbow flexor and extensor muscle groups. The exercises should be done 3 times per week and should take 
about 30 minutes to complete. They will be instructed to do the strengthening exercises and practice pinching 
using the table-top device and the task board to practice producing pinch force in specific locations that 
simulate the position of an ATM machine, horizontal and vertical zippers, using a fork, electric plug, remote 
control, and a key. All of the instructions for performing the exercises will be provided and each participant will 
practice the home exercises at the first test session. The participants will receive a log- book to document their 
participation in the exercise program. The participants will not be able to keep the exercise weights, brace, 
pinch meter, or table-top device. They will be used for other participants who are enrolled in the study over the 
next 2 years. The equipment in the exercise kit will be cleaned with anti-bacterial soap after use by individual 
participants.  
 
Measurement of muscle structure and function: Quantitative measurements of UE impairment will be recorded 
in the UE Lab. These measures include: muscle activation patterns with surface and fine- wire electrodes; and 
muscle strength using commercially available force transducers. A standardized test (Canadian Occupational 

Performance Measure) designed to detect self- perceived changes in performance over time will be 
administered by the examiner. In the test, participants will be asked to identify daily activities they want to be 
able to do and those which are difficult to complete to your satisfaction. The questions will relate to self-care, 
productivity, and leisure activities. This survey will be completed by the examiner before and after the training 
program.  
 
The participants will have an fMRI study to determine if the training program or the tendon transfer procedure 
produced changes in the brain compared to the control participants (non-impaired and SCI without tendon 
transfer surgery). During fMRI, the participants will lie on an MR table within the magnet and will be asked to lie 
as motionless as possible while they perform the task. The participant may also be fitted with a bite bar (made 
of dental impression material) to keep the head immobile during the scans. fMRI will be obtained during an 
active motor task during which participants are asked to perform lateral pinch tasks, or attempt upper limb 
movements. These tasks will be done at a submaximal level and participants will have feedback for the level of 
effort from the examiner. 
 
We will minimize risk by using research procedures that are routinely used in the clinical management of 
persons with tetraplegia. The testing procedures are minimal risk and the participants may improve their pinch 
strength after the home program.  
 
 
We will use video recording to document upper extremity motor performance during our clinical evaluation. The 
primary purpose of this information will be to document the testing procedures. However, these videos may be 
shown at scientific meetings. Participants will provide informed consent for all video recordings. Videos will be 
digitally stored on a password-protected computer. No personal health information will be linked to the video as 
they will be labeled using a unique patient identification codes. Videos will only include the participants arm 
and hand. 
 
There is no standard treatment that is being withheld. All of the participants will have completed conventional 
clinical rehabilitation following their tendon transfer procedure. There are currently no post-  
rehabilitation options for patients to participate in after discharge. The home exercise program will not be 
continued following the 10-week participation time and the equipment must be returned. 
 
Study Endpoint: Individuals who participate in the study will be monitoring their pinch strength during the 10-
week exercise phase of the study and will be aware of any negative effects of exercise, such as losing strength. 
It is unlikely there will be a loss of function during a 10-week exercise program. This study will end once all the 
participants are enrolled or the funded project period ends. 
 
Statistical analyses 
The main outcome measures for the fMRI data will be brain activation defined by intensity and cluster size in 
response to performing elbow flexion and pinch. Second level analyses will be mixed models effects derived 
using FSL FLAME for within participants (pre to post intervention) as well as cross-sectional (non impaired vs. 
SCI-ns; SCI-ns vs. SCI+TT) individual models (with outlier de-weighting and standard settings). Separately, T1 
and T2 voxelwise models will regress EMG pinch amplitude for that time-point onto brain data to examine 
neural correlates of our standard EMG outcome metric. The difference between T1 and T2 will be tested 
similarly (fMRI con images and EMG calculated as [pre-post/pre+post]) before regressing EMG onto voxel-
wise brain data.  
Pinch and elbow extension strength. Pinch force is sampled simultaneously with the EMG data. A custom 
MATLAB program is used to locate the peak force that is maintained for at least 0.5 sec during the 10 sec trial. 
Mean pinch force is expressed in newtons (1 lb. = 4.454 N) before and after the training period. 
EMG amplitude analysis. The EMG signals recorded during maximal pinch and maximal elbow flexion will be 
quantified by calculating a root-mean-square value over a 0.5 sec interval during peak force production. The 
ratio of the EMG amplitudes during maximal pinch to those during maximal elbow flexion will be calculated to 
normalize the EMG signals. During maximum pinch effort, the normalized EMG signals will be used to 
compare the amplitude of the transferred Br activation before and after the training program in each of the trials 

and between participants. The normalized EMG activation will be expressed as a percent of the maximum 
voluntary contractions (MVC).