Brain Stimulation + Behavioral Training for Peripheral Nerve Injury

Recruiting at 3 trial locations

Overseen By Scott H Frey, Ph.D., Ed.M.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Missouri-Columbia

Disqualifiers: Brain trauma, Psychiatric conditions, Neurological conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to aid recovery from peripheral nerve injuries, such as those from hand transplants or severe hand injuries. It combines special exercises with a gentle brain stimulation technique called transcranial direct current stimulation (tDCS) to determine if it can enhance hand function. This approach includes Modified Constraint Induced Movement Therapy, which involves specific exercises to improve movement. Individuals who have undergone hand transplants, reattachments, or nerve repairs and continue to experience difficulties in regaining normal hand function may be suitable candidates, particularly if about a year has passed since their surgery. As an unphased trial, this study provides a unique opportunity to investigate innovative recovery methods.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this technique is safe for improving functional recovery in peripheral nerve injuries?

Research has shown that Modified Constraint Induced Movement Therapy (CIMT) is generally safe. This therapy involves using the affected limb more while limiting the use of the other limb, and studies have found it can improve movement without causing major side effects.

Transcranial Direct Current Stimulation (tDCS) is also considered safe. Reviews indicate that tDCS, a non-invasive method of stimulating the brain, does not cause serious side effects. It can help the brain reorganize without damaging brain tissue.

Both CIMT and tDCS have strong safety records. They are well-tolerated and can aid in motor recovery without major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential of combining bi-hemispheric transcranial direct current stimulation (tDCS) with modified Constraint Induced Movement Therapy (CIMT) to improve hand function in patients with chronic peripheral nerve injuries and those who have undergone hand transplantation or replantation. Unlike traditional therapies that primarily focus on physical rehabilitation, this approach uses tDCS to stimulate both hemispheres of the brain, potentially enhancing neural plasticity and recovery. By integrating this brain stimulation technique with CIMT, which encourages the use of the affected limb, the trial aims to determine if this dual approach can break through recovery plateaus seen in conventional treatments.

What evidence suggests that this trial's treatments could be effective for peripheral nerve injury?

This trial will evaluate the combination of modified Constraint Induced Movement Therapy (CIMT) with transcranial direct current stimulation (tDCS) to improve hand and arm function in patients with peripheral nerve injuries and those who have undergone hand transplantation or replantation. Studies have shown that modified CIMT aids individuals recovering from strokes and other brain injuries by encouraging movement of the weaker hand while limiting the use of the stronger one. Research indicates that adding tDCS, which gently stimulates the brain, to rehabilitation exercises can further enhance hand recovery. Together, these treatments aim to help the brain adapt and improve recovery for those with nerve injuries or after hand transplants. Early findings suggest these methods can make everyday arm and hand activities easier. ^{4 6 7 8 9}

Who Is on the Research Team?

Scott H Frey, Ph.D., Ed.M.

Principal Investigator

University of Missouri-Columbia

Are You a Good Fit for This Trial?

This trial is for people who've had certain hand surgeries like transplants or nerve repairs and are in the later stages of recovery (about a year to a year and a half post-surgery). It's not for those with severe brain injuries, serious mental health issues, chronic neurological conditions, pregnancy, seizure history, or specific implants.

Inclusion Criteria

My hand was reattached after amputation and I'm 12-18 months post-surgery.

I had surgery for a severe forearm cut and it's been 12-18 months since.

I had a hand transplant over a year ago and have recovered.

Exclusion Criteria

Individuals with metallic implants above the chest

Individuals with certain implanted medical devices

I have had seizures or unexplained fainting episodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT) to enhance functional recovery

2 weeks

Follow-up

Participants are monitored for changes in upper limb movement and function using actigraphy and functional tests

6 months

Post intervention at week 1, 1 month, 3 months, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Modified Constraint Induced Movement Therapy
• Transcranial Direct Current Stimulation

Trial Overview The study tests if combining behavior training with non-invasive brain stimulation called tDCS can help the brain adapt better after hand surgery. Participants will undergo Transcranial Direct Current Stimulation along with Modified Constraint Induced Movement Therapy.

How Is the Trial Designed?

Group I: Transplantation/Replantation Patients Active Control 2 Interventions

Can plateaued hand function in hand transplantation patients/hand replantation patients in the chronic stage of recovery be facilitated by use of bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT)?

Group II: Actigraphy Testing Active Control 1 Intervention

We will acquire a set of actigraphy data from a group of hand transplant/replant patients and unilateral, adult amputees in order to evaluate typical patterns of limb use prior to hand transplantation and to investigate prosthesis utilization.

Group III: Nerve Injury Patients active Active Control 2 Interventions

Can plateaued hand function in peripheral nervous system injuries in the chronic stage of recovery be facilitated by use of bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT)?

Modified Constraint Induced Movement Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Constraint-Induced Movement Therapy for:

• Stroke rehabilitation
• Upper limb rehabilitation

Approved in European Union as Modified CIMT for:

• Stroke rehabilitation
• Upper limb rehabilitation
• Peripheral nerve injuries

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Christine M. Kleinert Institute for Hand and Microsurgery

Collaborator

Trials

11

Recruited

970+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

A modified constraint-induced movement therapy (mCIMT) program, involving 2 hours of treatment per day for 2 weeks, showed greater improvements in motor function and arm use compared to conventional rehabilitation in 66 stroke patients with hemiparesis.

The mCIMT group not only demonstrated significant improvements immediately after treatment but also maintained these benefits at a 3-month follow-up, indicating its potential as an effective rehabilitation strategy for chronic stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity modified constraint-induced movement therapy versus conventional therapy for upper extremity rehabilitation after stroke: a multicenter trial. Smania, N., Gandolfi, M., Paolucci, S., et al.[2016]

A survey of 169 clinicians revealed that while Constraint-Induced Movement Therapy (CIMT) is widely used for upper limb recovery after stroke and brain injury, many do not implement it as originally designed, with only 43.2% using mitt restraints as recommended.

Most clinicians (88.8%) incorporate intensive graded practice in their CIMT programs, indicating a strong understanding of effective rehabilitation strategies, but there is a need for improved training to ensure adherence to the full CIMT protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constraint-induced movement therapy for upper limb recovery in adult neurorehabilitation: An international survey of current knowledge and experience. Christie, LJ., McCluskey, A., Lovarini, M.[2020]

Constraint Induced Movement Therapy (CIMT) significantly improved the use of the paretic upper limb in individuals with severe hemiparesis, as evidenced by increased scores on the Graded Motor Activity Log (GMAL) and decreased performance time on the Graded Wolf Motor Function Test (GWMFT) after a 2-week intervention.

Improvements in kinematic variability during various tasks suggest enhanced interjoint coordination of the upper limb, indicating that CIMT can be effective even for individuals with chronic severe hemiparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shoulder complex and trunk coordination of individuals with severe hemiparesis following a constraint-induced movement therapy protocol: A case series. Pereira, ND., Lixandrão, MC., Morris, D., et al.[2023]

The case report demonstrated that electromyography-triggered neuromuscular stimulation (EMG-stim) can be feasibly combined with constraint-induced movement therapy (CIMT) in a 72-year-old man who was 10 years post-stroke, despite not meeting traditional CIMT criteria.

The combination of EMG-stim and CIMT led to significant improvements in motor behavior, muscle activity, and wrist range of motion, along with changes in brain representation of the muscle, indicating potential benefits for individuals with low functional abilities after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of electromyography-triggered neuromuscular stimulation as an adjunct to constraint-induced movement therapy. Fritz, SL., Chiu, YP., Malcolm, MP., et al.[2016]

Constraint-induced movement therapy (CIMT) significantly improved motor function in stroke patients in the short term, with the CIMT group showing faster performance and greater functional ability compared to traditional rehabilitation.

While CIMT was effective immediately after treatment, the long-term benefits were not sustained, as the control group continued to improve, leading to no significant differences between the groups at the six-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short- and long-term outcome of constraint-induced movement therapy after stroke: a randomized controlled feasibility trial. Dahl, AE., Askim, T., Stock, R., et al.[2016]

Constraint-induced movement therapy (CIMT) significantly improved real-world limb use in patients with chronic hemiparetic multiple sclerosis (MS), showing a large effect size compared to complementary and alternative medicine (CAM).

CIMT also induced positive changes in white matter integrity in specific brain regions, suggesting it may help reverse adverse effects of MS on brain structure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 2: Effect on White Matter Integrity. Barghi, A., Allendorfer, JB., Taub, E., et al.[2019]

In a study involving 52 stroke patients, high-intensity constraint-induced movement therapy (CIMT) did not lead to better motor recovery compared to traditional therapy, and in fact, resulted in less improvement at 90 days post-stroke.

The findings suggest that higher doses of motor training, particularly in the early stages of stroke rehabilitation, may not be more beneficial and highlight the need for careful control of therapy intensity in future motor intervention trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS): A single-center RCT. Dromerick, AW., Lang, CE., Birkenmeier, RL., et al.[2022]

In a study involving 36 participants with chronic median and ulnar nerve injuries, occupation-based practice during modified constraint-induced movement therapy led to significantly better improvements in hand function compared to rote exercise-based practice.

The occupation-based group showed greater enhancements in subjective measures of performance and satisfaction immediately after the intervention and maintained better outcomes in objective measures like box and block and static two-point discrimination at follow-up, highlighting the importance of meaningful activities in rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occupation-based intervention versus rote exercise in modified constraint-induced movement therapy for patients with median and ulnar nerve injuries: a randomized controlled trial. Rostami, HR., Akbarfahimi, M., Hassani Mehraban, A., et al.[2018]

Modified constraint induced movement therapy (m-CIMT) significantly improved upper extremity function in acute stroke patients compared to conventional rehabilitation therapy, as shown by clinical assessments like the Fugl-Meyer motor assessment and action research arm test.

Neurophysiological measures, such as motor evoked potentials, also demonstrated significant improvements in the m-CIMT group, suggesting that this therapy may enhance both functional recovery and underlying neural mechanisms in stroke rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of modified constraint-induced movement therapy in acute stroke. El-Helow, MR., Zamzam, ML., Fathalla, MM., et al.[2022]

Constraint-induced movement therapy (CIMT) has shown positive outcomes for some stroke survivors, but its adoption in clinical practice is limited due to barriers like resource intensity and therapist factors.

There is ongoing debate about whether the benefits of CIMT are specifically due to the protocol itself or simply the result of intense, task-specific therapy focused on the affected upper extremity, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barriers to the implementation of constraint-induced movement therapy into practice. Viana, R., Teasell, R.[2022]

Modified constraint induced movement therapy (m-CIMT) significantly improved upper extremity function in stroke patients, as evidenced by substantial gains in the Wolf Motor Function Test (WMFT) and Fugl-Meyer assessment (FMA) scores after 2 weeks of therapy.

The study involved 40 sub-acute stroke subjects, with the m-CIMT group showing marked improvements compared to the control group, indicating that m-CIMT is an effective intervention for enhancing motor function in affected arms post-stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial. Singh, P., Pradhan, B.[2021]

A preliminary phase II trial with 20 adults showed that Constraint-Induced Movement Therapy (CIMT) significantly improved real-world use of the affected arm in patients with multiple sclerosis (MS), with an average increase of 2.7 points on the Motor Activity Log compared to only 0.5 points in the complementary and alternative medicine (CAM) group.

The benefits of CIMT were not only significant but also long-lasting, as improvements were maintained at a 1-year follow-up, and the therapy was well tolerated with no reported adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Randomized Controlled Trial of Constraint-Induced Movement Therapy in Multiple Sclerosis. Part 1: Effects on Real-World Function. Mark, VW., Taub, E., Uswatte, G., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9219327/

Effectiveness of modified constraint-induced movement ... The outcome of this evaluation support that mCIMT significantly improves the upper limb function of stroke patients. Moreover, group mCIMT modality and TR ( ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11395467/

Constraint-Induced Movement Therapy (CIMT) and Neural ... Constraint-induced movement therapy (CIMT) enhances the functional use of the impaired limb and has emerged as a beneficial intervention for hemiplegic CP.

3. bfpt.springeropen.com bfpt.springeropen.com/articles/10.1186/s43161-024-00238-y

Effect of modified constraint-induced movement therapy along ... This preliminary study revealed that modified CIMT may be a feasible and effective alternative for hand rehabilitation in incomplete tetraplegia.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1474442214701607

Review Constraint-induced movement therapy after stroke The original and modified types of CIMT have beneficial effects on motor function, arm–hand activities, and self-reported arm–hand functioning in daily life, ...

5. researchgate.net researchgate.net/publication/343377521_The_Effect_of_Modified_Constraint-Induced_Movement_Therapy_on_Upper_Extremity_Function_of_a_Patient_With_Severe_Acquired_Brain_Injury

(PDF) The Effect of Modified Constraint-Induced Movement ... Results:‌ Improvement in the upper extremity function of a patient with chronic and severe ABI can be achieved by using the modified CIMT.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10151521/

The effect and safety of constraint-induced movement ... Our results showed that CIMT combined with conventional rehabilitation (CR) was superior to CR in improving MAL-AOU and MAL-QOM scores.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11211381/

Global research hotspots and trends in constraint-induced ... Improvement of motor function in stroke patients through various forms of constraint-induced movement therapy (CITM) has been recognized as safe ...

8. mdpi.com mdpi.com/1422-0067/25/17/9403

Constraint-Induced Movement Therapy (CIMT) and Neural ... This work demonstrates the mechanistic effects of CIMT and NPC transplantation and advocates for their combined therapeutic potential in addressing hemiplegic ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06910904

CONSTRAINT-INDUCED MOVEMENT THERAPY (CIMT) ... This study aimed to compare the effects of Constraint-Induced Movement Therapy (CIMT) and Mirror Therapy (MT) on hand function and spasticity in individuals ...