Brain Stimulation + Behavioral Training for Peripheral Nerve Injury

Recruiting at 2 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

Trial Summary

What is the purpose of this trial?

This study adopts a strategy that has arisen from basic neuroscience research on facilitating adaptive brain plasticity and applies this to rehabilitation to improve functional recovery in peripheral nervous system injuries (including hand transplantation, hand replantation, and surgically repaired upper extremity nerve injuries). The technique involves combining behavioral training with transcranial direct current stimulation (tDCS)-a non-invasive form of brain stimulation capable of facilitating adaptive changes in brain organization.

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 data supports the effectiveness of the treatment Brain Stimulation + Behavioral Training for Peripheral Nerve Injury?

Research shows that Constraint-Induced Movement Therapy (CIMT) is effective for improving arm and hand function in people recovering from strokes and brain injuries. This suggests that similar approaches, like the one in this trial, might help with nerve injuries too. ^{1 2 3 4 5}

Is the combination of brain stimulation and behavioral training for peripheral nerve injury safe for humans?

Constraint-induced movement therapy (CIMT) and its modified versions have been used safely in stroke rehabilitation to improve arm function, suggesting that these therapies are generally safe for human use. ^{6 7 8 9 10}

How is Modified Constraint-Induced Movement Therapy different from other treatments for peripheral nerve injury?

Modified Constraint-Induced Movement Therapy (CIMT) is unique because it involves intensive practice using the affected limb while restricting the use of the unaffected limb, which encourages the brain to adapt and improve function. This approach is different from traditional therapies that may not focus as intensively on using the affected limb. ^{1 2 6 11 12}

Research Team

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

Principal Investigator

University of Missouri-Columbia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2019]

2. England 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. [2018]

3. Australia pubmed.ncbi.nlm.nih.gov

Constraint-induced movement therapy for upper limb recovery in adult neurorehabilitation: An international survey of current knowledge and experience. [2020]

4. United States 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Feasibility of electromyography-triggered neuromuscular stimulation as an adjunct to constraint-induced movement therapy. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Reduced-intensity modified constraint-induced movement therapy versus conventional therapy for upper extremity rehabilitation after stroke: a multicenter trial. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS): A single-center RCT. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of modified constraint-induced movement therapy in acute stroke. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

10. India pubmed.ncbi.nlm.nih.gov

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

11. United States 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. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Short- and long-term outcome of constraint-induced movement therapy after stroke: a randomized controlled feasibility trial. [2016]