Spinal Cord InjuryNCT02768103
Neural Adaptation After Tendon Transfer and Training in Tetraplegia
A study testing task-based training in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The number of people in the United States who have survived SCI is estimated to be approximately 273,000 persons. Around 50% of the injuries are to the cervical spine resulting in tetraplegia. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- task-based training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to 30 Jun 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Individuals with a clinical diagnosis of SCI cervical level 4-7, complete or incomplete injuries, who have completed conventional therapy and be at least 1-year post-surgery, are eligible for the study.
- Participants must have had Br to FPL tendon transfer, be willing to participate in a 10 week exercise program, have adequate assistance or be independent in setting up exercise equipment (weight cuffs, functional tasks), and be available for two measurement sessions.
- Women and minorities may be included in the study if they meet the inclusion criteria.
- Non-Veteran participants who meet the selection criteria will be included to expand the available number of subjects.
Who cannot join
- More than one tendon transfer to the thumb to restore pinch but not if they have other tendon transfer procedures on the same upper limb.
- Other exclusion criteria include pain that would limit their ability to perform the activities, spasticity in the upper limb, or spinal cord injury level above C4 or below C7 as their pattern of weakness will be substantially different.
- Subjects who are participating in other research studies that include exercise programs for the upper limb or drug studies that affect their response to exercise will also be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Palo Alto Health Care System, Palo Alto, CA
Palo Alto, California, 94304-1290
About this study
Official title: Evaluating Neural Adaptation After Tendon Transfer and Task-based Training in SCI
The number of people in the United States who have survived SCI is estimated to be approximately 273,000 persons. Around 50% of the injuries are to the cervical spine resulting in tetraplegia. An important rehabilitation goal in this population is recovery of upper limb function, which could decrease medical costs and improve their quality of life. Re-establishing active grasp and pinch strength to the hand can be accomplished by surgeries that transfer the tendon of a strong muscle to restore strength to a paralyzed muscle, but the outcomes of the surgeries are variable. The investigators have demonstrated in an ongoing study, the functional gains after surgery can be improved with a focused therapy program to retrain the transferred muscle. The propose of this study is to examine the cortical mechanisms that drive successful muscle re-education after surgery. Understanding the neural (brain) activity associated with functional performance can help to predict who will respond to therapy and will guide evidence-based rehabilitation programs to improve upper limb function in tetraplegia.
Read the detailed description
Restoring upper limb function is rated among the highest priorities for individuals with tetraplegia. Re-establishing active grasp and pinch strength to the hand can be accomplished by tendon transfer procedures in which the tendon of a strong proximal muscle is surgically re-attached to the tendon of a paralyzed muscle. A common procedure to restore lateral (key) pinch is to transfer the distal tendon of one of the three elbow flexor muscles, the brachioradialis (Br) to the tendon of the paralyzed thumb flexor, the flexor pollicis longus (FPL). Recovery of functional pinch depends on how well the patient learns to activate the Br to flex the thumb through its new distal attachment, and also to control flexion at the elbow through its proximal attachment. The investigators' previous work shows that Br to FPL recipients do not activate the transferred Br fully and may not reach optimal functional status on their own or with traditional therapies. The investigators propose that participation in a postoperative task-based training program will drive cortical changes that impact functional (pinch) ability.
Recent studies of individuals with cervical SCI show substantial cortical reorganization can occur after the injury, but neural substrates of motor learning after tendon transfer have not been studied. For these patients, very little is known about what functional brain changes accompany improved performance in response to additional intervention. The Br to FPL transfer alters the central feedback from the periphery and may permit new or adaptive neural pathways that can achieve greater functional use of the tendon transfer. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) have become important tools for understanding plasticity in the neuromuscular system and for assessing the neural underpinnings of successful novel interventions. The objective of the proposed study is to identify the neural pattern that is associated with the best functional outcomes (highest pinch force) after Br to FPL transfer. The investigators will use fMRI and functional performance measures to find neural predictors and correlates of muscle re-education. That is, the investigators expect that successful postoperative muscle re-education will depend on increased cortical drive to the transferred Br in combination with new synergists, and this will be reflected in the neural imaging results.
The purpose of the study is to evaluate neural activity from Br to FPL transfer recipients after conventional therapy and in response to an additional task-based training home program that aims to improve voluntary activation of the transferred Br in functional pinch tasks. The 10-week training program is under evaluation in RRD Pilot (B0583P) study and includes producing pinch force in different upper limb postures, biofeedback from a pinch dynamometer, and practicing selected pinch tasks. The investigators anticipate that increases in the amplitude and distribution of fMRI blood oxygen level dependent (BOLD) responses in sensorimotor cortices will underlie improved motor control post-surgically and following successful intervention to promote motor relearning.
Specific Aims
- Define the cortical representation of pre-training pinch function in SCI patients. The investigators will quantify the pattern (location, volume and intensity) of cortical activation associated with voluntary pinch in individuals who are one-year post Br to FPL tendon transfer surgery and a conventional therapy program. The investigators hypothesize (H1) greater volume and intensity of brain activation will correlate to better pinch function measured by pinch strength and the magnitude Br activation in pinch. Secondary analyses will determine if the location of the brain activation varies with pinch function (force) and specificity relative to voluntary elbow flexion.
- Evaluate the cortical response to the task-based home therapy program. Correlates of task-based adaptation from pre- to post-training will be assessed using fMRI. H2: Greater activation (intensity and volume) in the primary motor cortex (M1) and sensory cortex will translate to increased voluntary activation of the transferred Br in pinch compared to elbow flexion. Task-based training outcome measures will include isometric pinch force magnitude, EMG quantification of Br activation in pinch and elbow flexion.
- Determine neural signatures of surgical and training induced motor improvements. H3: After directed task-based training, brain activity during voluntary pinch will extend to adjacent areas (larger representation, greater activity), in sensorimotor brain areas, facilitating the ability to voluntarily increase the transferred Br activation in pinch. Secondary analyses will contrast size and activation level of brain changes with pinch activation in patients who receive training relative to non-impaired and non-surgical participants.
The postoperative therapy protocols after tendon transfer procedures are not well defined, inconsistently applied, and lack evidence for their effectiveness. The study proposed here will investigate cortical change to assess outcome dependent plasticity. Thus, it may be possible to predict why some individuals do not re-train the transferred muscle as well as others. Establishing this relationship can lead to understanding the mechanisms of successful interventions and may identify brain based dynamics that could become the focus of future treatments (e.g. biofeedback, brain stimulation, etc.).
- Conditions
- Spinal Cord Injury
- Being tested
- task-based training
- Keywords
- upper extremity, spinal cord injury, surgical reconstruction, MRI, functional, rehabilitation
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
task-based trainingBehavioural
The 10-week training program is designed to incorporate requirements of motor learning and includes activities that require learning to coordinate the transferred Br with other synergists by producing pinch force in different upper limb postures and in a range of pinch openings. Biofeedback using a pinch dynamometer in self-selected postures provides feedback and knowledge of progress to the participant. A task board is used for practicing task-specific activities such as opening and closing zippers, using a remote, an ATM card, a key, and an electrical plug and focuses on pinch in dynamic conditions that require modulating force and maintaining specific positions. The pinch-pin device requires closing pinch-pins (clothes pin) of variable resistance ranging from approximately 1 to 8 lbs and placing them on rods arranged at different positions in the work space.
| Study group | Role | What they receive |
|---|---|---|
| SCI transfer + training | Experimental | Individuals with tetraplegia and brachioradialis to flexor pollicis longus transfer will participate in 10 week home training program to improve surgical outcome (pinch strength) Receives: Behavioral: task-based training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pinch Force
Pinch force recorded in newtons from force sensor mounted to a custom grip
Measured: after 10 weeks home exercise program with task-based training
Functional MRI BOLD Signal From Motor Cortex
A block design with 10 seconds of rest alternating with 10 seconds of functional movement for 6 minutes will be followed. Participants have visual cues to instruct them in the timing and sequence of the tasks to be performed. Scan time to include a session of elbow flexion and a session for pinch is about 20 minutes. 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 subjects (pre to post intervention) as well as cross-sectional (non impaired vs. SCI-ns; SCI-ns vs. SCI+TT) individual models (with outlier deweighting and standard settings).
Measured: after 10 week home exercise program with task-based training
Secondary outcomes (1)
Fine-wire Electromyography of Transferred Brachioradialis Muscle (to Paralyzed Thumb Flexor)
EMG signal recorded from fine-wire (intramuscular) electrodes normalized to a maximum voluntary contraction
Measured: after 10 week home exercise program with task-based training
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study startMay 2016
- Primary completion30 Jun 2018
- Study completion30 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants complete 10 week task based training in home setting.
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Mary E Johanson, DPT, Principal investigator, VA Palo Alto Health Care System, Palo Alto, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02768103
- Sponsor's protocol ID
- N1772-P
- Status last verified
- Oct 2022
- First submitted
- 6 May 2016
- Last updated
- 15 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Johanson ME, Dairaghi CA, Hentz VR. Evaluation of a Task-Based Intervention After Tendon Transfer to Restore Lateral Pinch. Arch Phys Med Rehabil. 2016 Jun;97(6 Suppl):S144-53. doi: 10.1016/j.apmr.2015.12.032.
PubMed 27233589
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Neural Adaptation After Tendon Transfer and Task-based Training in SCI
- ClinicalTrials.gov ID
- NCT02768103
- Acronym / sponsor ID
- N1772-P
- Conditions
- Spinal Cord Injury
- Keywords
- upper extremity, spinal cord injury, surgical reconstruction, MRI, functional, rehabilitation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- May 2016 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 30 Jun 2018 (actual)
- First posted
- 11 May 2016 (estimated)
- Results
- Posted 15 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The number of people in the United States who have survived SCI is estimated to be approximately 273,000 persons. Around 50% of the injuries are to the cervical spine resulting in tetraplegia. An important rehabilitation goal in this population is recovery of upper limb function, which could decrease medical costs and improve their quality of life. Re-establishing active grasp and pinch strength to the hand can be accomplished by surgeries that transfer the tendon of a strong muscle to restore strength to a paralyzed muscle, but the outcomes of the surgeries are variable. The investigators have demonstrated in an ongoing study, the functional gains after surgery can be improved with a focused therapy program to retrain the transferred muscle. The propose of this study is to examine the cortical mechanisms that drive successful muscle re-education after surgery. Understanding the neural (brain) activity associated with functional performance can help to predict who will respond to therapy and will guide evidence-based rehabilitation programs to improve upper limb function in tetraplegia.
Detailed description
Restoring upper limb function is rated among the highest priorities for individuals with tetraplegia. Re-establishing active grasp and pinch strength to the hand can be accomplished by tendon transfer procedures in which the tendon of a strong proximal muscle is surgically re-attached to the tendon of a paralyzed muscle. A common procedure to restore lateral (key) pinch is to transfer the distal tendon of one of the three elbow flexor muscles, the brachioradialis (Br) to the tendon of the paralyzed thumb flexor, the flexor pollicis longus (FPL). Recovery of functional pinch depends on how well the patient learns to activate the Br to flex the thumb through its new distal attachment, and also to control flexion at the elbow through its proximal attachment. The investigators' previous work shows that Br to FPL recipients do not activate the transferred Br fully and may not reach optimal functional status on their own or with traditional therapies. The investigators propose that participation in a postoperative task-based training program will drive cortical changes that impact functional (pinch) ability.
Recent studies of individuals with cervical SCI show substantial cortical reorganization can occur after the injury, but neural substrates of motor learning after tendon transfer have not been studied. For these patients, very little is known about what functional brain changes accompany improved performance in response to additional intervention. The Br to FPL transfer alters the central feedback from the periphery and may permit new or adaptive neural pathways that can achieve greater functional use of the tendon transfer. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) have become important tools for understanding plasticity in the neuromuscular system and for assessing the neural underpinnings of successful novel interventions. The objective of the proposed study is to identify the neural pattern that is associated with the best functional outcomes (highest pinch force) after Br to FPL transfer. The investigators will use fMRI and functional performance measures to find neural predictors and correlates of muscle re-education. That is, the investigators expect that successful postoperative muscle re-education will depend on increased cortical drive to the transferred Br in combination with new synergists, and this will be reflected in the neural imaging results.
The purpose of the study is to evaluate neural activity from Br to FPL transfer recipients after conventional therapy and in response to an additional task-based training home program that aims to improve voluntary activation of the transferred Br in functional pinch tasks. The 10-week training program is under evaluation in RRD Pilot (B0583P) study and includes producing pinch force in different upper limb postures, biofeedback from a pinch dynamometer, and practicing selected pinch tasks. The investigators anticipate that increases in the amplitude and distribution of fMRI blood oxygen level dependent (BOLD) responses in sensorimotor cortices will underlie improved motor control post-surgically and following successful intervention to promote motor relearning.
Specific Aims
- Define the cortical representation of pre-training pinch function in SCI patients. The investigators will quantify the pattern (location, volume and intensity) of cortical activation associated with voluntary pinch in individuals who are one-year post Br to FPL tendon transfer surgery and a conventional therapy program. The investigators hypothesize (H1) greater volume and intensity of brain activation will correlate to better pinch function measured by pinch strength and the magnitude Br activation in pinch. Secondary analyses will determine if the location of the brain activation varies with pinch function (force) and specificity relative to voluntary elbow flexion.
- Evaluate the cortical response to the task-based home therapy program. Correlates of task-based adaptation from pre- to post-training will be assessed using fMRI. H2: Greater activation (intensity and volume) in the primary motor cortex (M1) and sensory cortex will translate to increased voluntary activation of the transferred Br in pinch compared to elbow flexion. Task-based training outcome measures will include isometric pinch force magnitude, EMG quantification of Br activation in pinch and elbow flexion.
- Determine neural signatures of surgical and training induced motor improvements. H3: After directed task-based training, brain activity during voluntary pinch will extend to adjacent areas (larger representation, greater activity), in sensorimotor brain areas, facilitating the ability to voluntarily increase the transferred Br activation in pinch. Secondary analyses will contrast size and activation level of brain changes with pinch activation in patients who receive training relative to non-impaired and non-surgical participants.
The postoperative therapy protocols after tendon transfer procedures are not well defined, inconsistently applied, and lack evidence for their effectiveness. The study proposed here will investigate cortical change to assess outcome dependent plasticity. Thus, it may be possible to predict why some individuals do not re-train the transferred muscle as well as others. Establishing this relationship can lead to understanding the mechanisms of successful interventions and may identify brain based dynamics that could become the focus of future treatments (e.g. biofeedback, brain stimulation, etc.).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants complete 10 week task based training in home setting.
| Arm | Type | Receives |
|---|---|---|
| SCI transfer + training | Experimental | Behavioral: task-based trainingIndividuals with tetraplegia and brachioradialis to flexor pollicis longus transfer will participate in 10 week home training program to improve surgical outcome (pinch strength) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Individuals with a clinical diagnosis of SCI cervical level 4-7, complete or incomplete injuries, who have completed conventional therapy and be at least 1-year post-surgery, are eligible for the study.
- Participants must have had Br to FPL tendon transfer, be willing to participate in a 10 week exercise program, have adequate assistance or be independent in setting up exercise equipment (weight cuffs, functional tasks), and be available for two measurement sessions.
- Women and minorities may be included in the study if they meet the inclusion criteria.
- Non-Veteran participants who meet the selection criteria will be included to expand the available number of subjects.
Key exclusion criteria (3 listed)
- More than one tendon transfer to the thumb to restore pinch but not if they have other tendon transfer procedures on the same upper limb.
- Other exclusion criteria include pain that would limit their ability to perform the activities, spasticity in the upper limb, or spinal cord injury level above C4 or below C7 as their pattern of weakness will be substantially different.
- Subjects who are participating in other research studies that include exercise programs for the upper limb or drug studies that affect their response to exercise will also be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| task-based trainingThe 10-week training program is designed to incorporate requirements of motor learning and includes activities that require learning to coordinate the transferred Br with other synergists by producing pinch force in different upper limb postures and in a range of pinch openings. Biofeedback using a pinch dynamometer in self-selected postures provides feedback and knowledge of progress to the participant. A task board is used for practicing task-specific activities such as opening and closing zippers, using a remote, an ATM card, a key, and an electrical plug and focuses on pinch in dynamic conditions that require modulating force and maintaining specific positions. The pinch-pin device requires closing pinch-pins (clothes pin) of variable resistance ranging from approximately 1 to 8 lbs and placing them on rods arranged at different positions in the work space. | Behavioural | SCI transfer + training |
Primary outcome
Pinch Force
Time frame: after 10 weeks home exercise program with task-based training
Pinch force recorded in newtons from force sensor mounted to a custom grip
Functional MRI BOLD Signal From Motor Cortex
Time frame: after 10 week home exercise program with task-based training
A block design with 10 seconds of rest alternating with 10 seconds of functional movement for 6 minutes will be followed. Participants have visual cues to instruct them in the timing and sequence of the tasks to be performed. Scan time to include a session of elbow flexion and a session for pinch is about 20 minutes. 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 subjects (pre to post intervention) as well as cross-sectional (non impaired vs. SCI-ns; SCI-ns vs. SCI+TT) individual models (with outlier deweighting and standard settings).
1 secondary outcome
Fine-wire Electromyography of Transferred Brachioradialis Muscle (to Paralyzed Thumb Flexor)
Time frame: after 10 week home exercise program with task-based training
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27233589Johanson ME, Dairaghi CA, Hentz VR. Evaluation of a Task-Based Intervention After Tendon Transfer to Restore Lateral Pinch. Arch Phys Med Rehabil. 2016 Jun;97(6 Suppl):S144-53. doi: 10.1016/j.apmr.2015.12.032.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary E Johanson, DPT principal investigator
VA Palo Alto Health Care System, Palo Alto, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing task-based training in people with Spinal Cord Injury, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pinch Force (time frame: after 10 weeks home exercise program with task-based training). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02768103, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2022.