Deep Brain Stimulation + Rehab for Stroke-related Arm Weakness

(RESTORE Trial)

Recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Enspire DBS Therapy, Inc.

Disqualifiers: Cerebrovascular events, Brain lesions, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

202 Participants Needed

Trial Summary

What is the purpose of this trial?

The RESTORE Stroke Study will evaluate the safety and effectiveness of DBS+Rehab for treating arm weakness and reduced function after a stroke.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Deep Brain Stimulation + Rehab for Stroke-related Arm Weakness?

Research shows that combining different types of electrical stimulation and robotic therapy can improve arm function in stroke patients. For example, studies have found that functional electrical stimulation and robotic-assisted therapy can help stroke survivors regain arm movement and control. While these studies don't directly involve deep brain stimulation, they suggest that combining brain and physical therapies can be beneficial for stroke recovery. ^{1 2 3 4 5}

Is Deep Brain Stimulation safe for treating stroke-related arm weakness?

While the specific safety data for Deep Brain Stimulation (DBS) in treating stroke-related arm weakness is not provided, similar treatments like vagus nerve stimulation paired with rehabilitation have been studied. These studies show that while there can be serious adverse events related to surgery, the treatment is generally well-tolerated and has been used safely in humans for improving arm function after stroke. ^{6 7 8 9 10}

How is Deep Brain Stimulation (DBS) different from other treatments for stroke-related arm weakness?

Deep Brain Stimulation (DBS) is unique because it involves implanting electrodes in the brain to directly stimulate specific areas, which can enhance brain plasticity and improve motor function. This is different from other treatments like transcranial magnetic stimulation or vagus nerve stimulation, which are non-invasive and work by stimulating the brain or nerves from outside the body. ^{9 11 12 13 14}

Eligibility Criteria

This trial is for individuals who had an ischemic stroke between 1 and 6 years ago, leading to ongoing weakness in one arm. It's not suitable for those with additional strokes affecting the arm or significant damage to certain brain areas like the brainstem, cerebellum, or thalamus.

Inclusion Criteria

I had a stroke 1-6 years ago and still have weakness in one arm.

Exclusion Criteria

My brain cancer affects critical areas like the brainstem.

I have had a stroke that affected my arm's movement.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Optimization

Each subject will be implanted with the DBS system and undergo DBS program optimization

4 weeks

Randomized Treatment

Subjects are randomized to test treatment or active-control treatment and participate in a five-month outpatient rehabilitation therapy program

20 weeks

Crossover Treatment

Subjects assigned to active-control treatment cross over to receive test treatment and participate in a second five-month therapy program

20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Deep Brain Stimulation
• Rehabilitation

Trial Overview The RESTORE Stroke Study is testing whether combining Deep Brain Stimulation (DBS) with rehabilitation therapy can improve arm strength and function after a stroke.

Participant Groups

Group I: DBS+Rehab Experimental Treatment 1 Intervention

Active-DBS combined with motor rehabilitation

Group II: Rehab Active Control 1 Intervention

Control-DBS combined with motor rehabilitation

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

Enspire DBS Therapy, Inc.

Lead Sponsor

Trials

2

Recruited

210+

Findings from Research

In a study involving 10 right-handed participants with chronic subcortical stroke, high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly improved lower limb motor function, with effects lasting at least one month after treatment.

The real rTMS treatment showed greater improvements in lower limb function compared to sham stimulation, indicating its potential as an effective rehabilitation strategy for stroke survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep repetitive transcranial magnetic stimulation with H-coil on lower limb motor function in chronic stroke: a pilot study. Chieffo, R., De Prezzo, S., Houdayer, E., et al.[2016]

In a study involving 40 patients with subacute ischemic stroke, both robot-assisted therapy combined with functional electrical stimulation (RAT+FES) and intensive conventional therapy led to significant improvements in arm function, but there were no differences in effectiveness between the two methods.

Patients with moderate impairment and detectable motor evoked potentials (MEPs) who started rehabilitation within 30 days post-stroke showed the most significant recovery, suggesting that early intervention is crucial for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a Robot-Assisted Arm Training Plus Hand Functional Electrical Stimulation on Recovery After Stroke: A Randomized Clinical Trial. Straudi, S., Baroni, A., Mele, S., et al.[2020]

In a preliminary trial with 12 subacute stroke patients, EMG-triggered multichannel functional electrical stimulation (EMG-MES) showed greater improvement in regaining control of voluntary movements compared to single-channel cyclic neuromuscular electrical stimulation (cNMES).

Participants receiving EMG-MES reported better outcomes in daily activities and arm-hand use, suggesting that this method may enhance rehabilitation effectiveness for stroke patients with moderate arm paresis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Four-Channel Functional Electrical Stimulation on Moderate Arm Paresis in Subacute Stroke Patients-Results from a Randomized Controlled Trial. Schick, T., Kolm, D., Leitner, A., et al.[2022]

In a study of 30 chronic stroke patients, electrical stimulation of only the extensor muscles (group B) led to a greater improvement in arm function compared to alternating stimulation of both extensor and flexor muscles (group A), with an average gain of 3.3 points versus 1.0 point on the Action Research Arm test.

Despite the observed differences in improvement, neither the functional gains nor the success rates for clinically relevant improvements were statistically significant between the two stimulation methods, indicating that both approaches may have similar efficacy in enhancing arm function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation of the upper limb in stroke: stimulation of the extensors of the hand vs. alternate stimulation of flexors and extensors. de Kroon, JR., IJzerman, MJ., Lankhorst, GJ., et al.[2019]

The combination of anodal transcranial direct current stimulation (tDCS) and robotic therapy was found to be safe and effective in improving upper limb function in an adult with unilateral spastic cerebral palsy, as demonstrated over 36 therapy sessions.

Significant improvements in reaching accuracy, as well as clinically meaningful gains in motor function measured by the Wolf Motor Function Test and Fugl-Meyer assessment, were observed immediately after therapy and were maintained six months later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined transcranial direct current stimulation and robotic upper limb therapy improves upper limb function in an adult with cerebral palsy. Friel, KM., Lee, P., Soles, LV., et al.[2018]

Vagus nerve stimulation (VNS) combined with rehabilitation was found to be safe and feasible for improving arm function in stroke patients, with all participants completing the therapy despite some serious adverse events related to surgery.

At 90 days post-therapy, patients receiving active VNS showed a significant improvement in upper limb function compared to the control group, with an 88% clinically meaningful response rate, suggesting that VNS may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Kimberley, TJ., Pierce, D., Prudente, CN., et al.[2019]

In a study involving stroke survivors with chronic arm weakness, Vagus Nerve Stimulation (VNS) combined with rehabilitation led to a significant improvement in upper extremity function, with an average increase of 5.0 points in the Fugl-Meyer Assessment score compared to 2.4 points in the control group.

The effectiveness of VNS treatment was consistent across various subgroups, including age, severity of impairment, and time since stroke, indicating that VNS could be a broadly applicable intervention for improving arm function in diverse stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial. Dawson, J., Engineer, ND., Cramer, SC., et al.[2023]

A fully implantable peripheral nerve stimulation system targeting the axillary nerve showed significant safety and efficacy in reducing chronic shoulder pain in stroke survivors, with 50% or greater pain reduction observed in all five participants after 6 and 12 months.

Participants also experienced improvements in pain interference and pain-free external rotation range of motion, with no serious adverse events reported over the 24-month follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully Implantable Peripheral Nerve Stimulation for Hemiplegic Shoulder Pain: A Multi-Site Case Series With Two-Year Follow-Up. Wilson, RD., Bennett, ME., Nguyen, VQC., et al.[2022]

The FDA has approved a paired vagus nerve stimulation (VNS) system that, when combined with rehabilitation therapy, significantly improves upper extremity function in patients with moderate-to-severe arm weakness after chronic ischemic stroke, as shown in a Phase III trial with an average follow-up of 3 years.

Patients receiving VNS therapy experienced a clinically meaningful improvement of at least six points on the Fugl-Meyer score, with about 50% achieving this response compared to only 25% in those receiving rehabilitation alone, indicating the potential effectiveness of VNS in enhancing recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke. Dawson, J., Abdul-Rahim, AH.[2022]

A 58-year-old male stroke survivor experienced significant relief from chronic shoulder pain after receiving electrical stimulation from a fully implanted microstimulator, with pain levels decreasing from 8/10 to 4/10 after 12 weeks and further to 3/10 at a 3-month follow-up.

The implantation procedure was safe and well tolerated, with no adverse events reported, suggesting that implanted peripheral nerve stimulation could be a promising treatment for poststroke shoulder pain, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation for treating chronic poststroke shoulder pain using a fully implanted microstimulator with internal battery. Yu, DT., Friedman, AS., Rosenfeld, EL.[2016]

Task-oriented electromyography-triggered stimulation significantly improved shoulder subluxation, muscle activation, and pain levels in hemiparetic stroke patients compared to cyclic functional electrical stimulation, based on a study of 20 participants over four weeks.

While the experimental group showed notable improvements, there were no significant differences in upper extremity function as measured by the Fugl-Meyer Assessment between the two groups, indicating that while the stimulation method is effective for certain outcomes, it may not enhance overall hand function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of electromyography-triggered electrical stimulation on shoulder subluxation, muscle activation, pain, and function in persons with stroke: A pilot study. Jeon, S., Kim, Y., Jung, K., et al.[2018]

New brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex of stroke patients, potentially improving motor function.

Activity-dependent stimulation, which tailors brain stimulation to the patient's neural or muscular activity, may offer even better outcomes compared to traditional neurorehabilitation methods, suggesting a promising direction for future stroke rehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New modalities of brain stimulation for stroke rehabilitation. Edwardson, MA., Lucas, TH., Carey, JR., et al.[2021]

Transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) have shown potential in enhancing upper-limb motor function after stroke by promoting brain plasticity and modifying cortical excitability.

Initial placebo-controlled trials indicate that both tDCS and rTMS can lead to temporary improvements in upper-limb function following a single session, suggesting that repeated sessions could be beneficial and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: a review. Kandel, M., Beis, JM., Le Chapelain, L., et al.[2016]

A systematic review of nine studies involving 371 stroke patients found that transcranial direct current stimulation (tDCS) combined with rehabilitation showed a small non-significant effect on upper extremity recovery, with effect sizes of +0.11 for impairments and +0.24 for activities.

The variability in tDCS methodologies and rehabilitation programs suggests that while there may be some benefit, the current evidence is not strong enough to confirm its efficacy, indicating a need for further research to identify which patients may benefit most from specific tDCS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis. Tedesco Triccas, L., Burridge, JH., Hughes, AM., et al.[2022]

References

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

Deep repetitive transcranial magnetic stimulation with H-coil on lower limb motor function in chronic stroke: a pilot study. [2016]

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

Effects of a Robot-Assisted Arm Training Plus Hand Functional Electrical Stimulation on Recovery After Stroke: A Randomized Clinical Trial. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Four-Channel Functional Electrical Stimulation on Moderate Arm Paresis in Subacute Stroke Patients-Results from a Randomized Controlled Trial. [2022]

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

Electrical stimulation of the upper limb in stroke: stimulation of the extensors of the hand vs. alternate stimulation of flexors and extensors. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Combined transcranial direct current stimulation and robotic upper limb therapy improves upper limb function in an adult with cerebral palsy. [2018]

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

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. [2019]

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

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial. [2023]

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

Fully Implantable Peripheral Nerve Stimulation for Hemiplegic Shoulder Pain: A Multi-Site Case Series With Two-Year Follow-Up. [2022]

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

Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke. [2022]

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

Electrical stimulation for treating chronic poststroke shoulder pain using a fully implanted microstimulator with internal battery. [2016]

11. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of electromyography-triggered electrical stimulation on shoulder subluxation, muscle activation, pain, and function in persons with stroke: A pilot study. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

New modalities of brain stimulation for stroke rehabilitation. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: a review. [2016]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Multiple sessions of transcranial direct current stimulation and upper extremity rehabilitation in stroke: A review and meta-analysis. [2022]