Deep Brain Stimulation for Stroke

Overseen By Elvira Pirondini, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Jorge Gonzalez-Martinez

Must not be taking: Anticoagulants, Anti-spasticity, Anti-epileptic, others

Disqualifiers: Neurological condition, Cancer, Cardiac, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 29 days

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to verify whether the use of deep brain stimulation can improve motor function of the hand and arm and speech abilities for people following a stroke. Participants will undergo a surgical procedure to implant deep brain stimulation electrode leads. The electrodes will be connected to external stimulators and a series of experiments will be performed to identify the types of movements that the hand and arm can make and how speech abilities are affected by the stimulation. The implant will be removed after less than 30 days. Results of this study will provide the foundation for future studies evaluating the efficacy of a minimally-invasive neuro-technology that can be used in clinical neuro-rehabilitation programs to restore speech and upper limb motor functions in people with subcortical strokes, thereby increasing independence and quality of life.

Will I have to stop taking my current medications?

Participants must not be on anti-spasticity or anti-epileptic medications during the study. If you are taking these, you will need to stop. The protocol does not specify about other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the treatment Deep Brain Stimulation (DBS) of the Motor Thalamus for stroke?

Research shows that Deep Brain Stimulation (DBS) of the thalamus is effective in reducing tremors in conditions like essential tremor and Parkinson's disease, with many patients experiencing significant improvement. This suggests that DBS could potentially help manage symptoms in other conditions, such as stroke, by targeting similar brain areas. ^{1 2 3 4 5}

Is deep brain stimulation of the thalamus generally safe for humans?

Deep brain stimulation (DBS) of the thalamus has been studied for conditions like Parkinson's disease and essential tremor. While it can improve symptoms, some patients experienced mild side effects that were manageable, and a few had more serious issues like brain bleeding or seizures. Device-related complications were common, sometimes requiring additional surgeries. ^{6 7 8 9 10}

How is Deep Brain Stimulation (DBS) of the Motor Thalamus different from other treatments for stroke?

Deep Brain Stimulation (DBS) of the Motor Thalamus is unique because it involves implanting electrodes in the brain to send electrical impulses, which can help manage symptoms like tremors. Unlike medications, which are taken orally or injected, DBS directly targets brain areas involved in movement control, offering a different approach for conditions like stroke where traditional treatments may be limited. ^{2 11 12 13 14}

Research Team

Jorge Gonzalez-Martinez, MD/PhD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for individuals who have had a subcortical stroke and are experiencing difficulties with speech and arm/hand movements. Candidates must be stable after their stroke and able to give informed consent. Specific details about age, time since stroke, or other health conditions that might affect eligibility are not provided.

Inclusion Criteria

Native English speaker

I had a stroke over 6 months ago and now have speech difficulties.

I have moderate to severe difficulty speaking clearly.

Exclusion Criteria

Patients who cannot undergo pre-operative MRIs or could not complete the pre-operative assessments

I am mentally capable of understanding and signing a consent form.

I am not taking any blood thinners.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Procedure

Participants undergo a surgical procedure to implant deep brain stimulation electrode leads

1 week

Treatment

Participants receive deep brain stimulation to assess motor and speech function improvements

29 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Deep Brain Stimulation (DBS) of the Motor Thalamus

Trial Overview The study tests if deep brain stimulation (DBS) of the motor thalamus can help restore speech and upper limb function in post-stroke patients. Participants will undergo surgery to implant electrodes for less than 30 days, during which the effects on movement and speech will be assessed.

Participant Groups

Group I: Deep Brain Stimulation of the Motor Thalamus Experimental Treatment 1 Intervention

Individuals who have speech and motor deficits due to a stroke.

Deep Brain Stimulation (DBS) of the Motor Thalamus is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Deep Brain Stimulation (DBS) for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Chronic pain
• Obsessive-compulsive disorder
• Treatment-resistant depression

Approved in United States as Deep Brain Stimulation (DBS) for:

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

Approved in Canada as Deep Brain Stimulation (DBS) for:

• Parkinson's disease
• Essential tremor
• Dystonia

Approved in Japan as Deep Brain Stimulation (DBS) for:

• Parkinson's disease
• Essential tremor

Who Is Running the Clinical Trial?

Jorge Gonzalez-Martinez

Lead Sponsor

Trials

1

Recruited

10+

Findings from Research

In a study of 46 patients treated with VIM deep brain stimulation (DBS) for essential tremor, 70% reported high satisfaction with the treatment, with a median score of 10 out of 10 for overall satisfaction and a significant long-term effect on tremor reduction.

The study found no significant increase in mortality among VIM-DBS patients compared to the general population, with a standard mortality ratio of 1.3, although one patient did commit suicide, raising questions about potential suicide risk associated with the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality. Børretzen, MN., Bjerknes, S., Sæhle, T., et al.[2021]

In a study involving four patients with posttraumatic and multiple sclerosis tremors, the use of dual deep brain stimulation (DBS) electrodes targeting both the VIM and VOA/VOP thalamic regions resulted in significant improvements in tremor symptoms across all tested conditions, with no tremor rebound observed after chronic stimulation.

The combination of VIM and VOA/VOP DBS showed greater symptom reduction compared to using either electrode alone, suggesting that targeting multiple areas may enhance treatment efficacy for tremors that do not respond well to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual electrode thalamic deep brain stimulation for the treatment of posttraumatic and multiple sclerosis tremor. Foote, KD., Seignourel, P., Fernandez, HH., et al.[2006]

Deep Brain Stimulation (DBS) in the ventral intermediate nucleus (VIM) of the thalamus effectively relieved tremor symptoms in all four patients with drug-resistant tremor, demonstrating significant tremor control.

The procedure was safe, with no serious adverse events reported; any transient adverse effects were quickly resolved by adjusting the stimulation parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation of thalamus for tremor control]. Nasser, JA., Falavigna, A., Alaminos, A., et al.[2009]

An 18-year-old man with severe action tremor following a traumatic brain injury experienced significant tremor suppression after undergoing deep brain stimulation (DBS) targeting the left ventral intermediate nucleus of the thalamus.

The procedure was performed without complications, suggesting that DBS may be a safe and effective treatment option for managing intractable posttraumatic tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for posttraumatic action tremor. Umemura, A., Samadani, U., Jaggi, JL., et al.[2009]

High-frequency stimulation of the ventral intermediate nucleus (Vim) was effective in reducing tremor in 88% of patients with Parkinson's disease and essential tremor, with 27 out of 43 thalami showing complete relief and 11 showing major improvement.

The procedure demonstrated a favorable safety profile, with only mild adverse effects that could be managed by adjusting the stimulation, making it a preferable option over thalamotomy for bilateral treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Benabid, AL., Pollak, P., Gervason, C., et al.[2022]

Unilateral deep brain stimulation (DBS) of the thalamus significantly improved tremor scores in patients with Parkinson's disease over a long-term follow-up period averaging 40 months, demonstrating its efficacy for treating medication-resistant tremor.

While there were some mild adverse effects, including two asymptomatic intracerebral hemorrhages, the overall safety profile was acceptable, with manageable stimulus-related reactions and necessary device replacements due to normal wear and tear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term safety and efficacy of unilateral deep brain stimulation of the thalamus for parkinsonian tremor. Lyons, KE., Koller, WC., Wilkinson, SB., et al.[2019]

Unilateral deep brain stimulation (DBS) of the VIM nucleus in the thalamus shows long-term efficacy in reducing essential tremor symptoms, with significant improvements noted in tremor scores at an average follow-up of 40.2 months after surgery.

While the treatment is effective for some patients, it is associated with device-related complications and a risk of loss of efficacy over time, necessitating additional surgical interventions in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Koller, WC., Lyons, KE., Wilkinson, SB., et al.[2022]

In a 5-year follow-up study of 38 patients with essential tremor (ET) and Parkinson's disease (PD), thalamic deep brain stimulation (DBS) showed significant long-term efficacy, with patients experiencing up to 100% improvement in tremors depending on the type of stimulation (unilateral or bilateral).

While DBS is generally safe, common adverse effects included paresthesia and pain for unilateral implants, and dysarthria and balance difficulties for bilateral implants, indicating that careful consideration is needed when opting for bilateral stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term evaluation of deep brain stimulation of the thalamus. Pahwa, R., Lyons, KE., Wilkinson, SB., et al.[2022]

A case of hyperhidrosis (excessive sweating) was observed as a side effect of a misplaced deep brain stimulation (DBS) electrode in a patient with essential tremor, highlighting a potential complication of DBS procedures.

The MRI revealed that the electrode was incorrectly placed near the hypothalamus, suggesting that high-frequency stimulation may activate sympathetic pathways, leading to hypothalamic dysfunction as a rare but significant side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperhidrosis due to deep brain stimulation in a patient with essential tremor. Case report. Diamond, A., Kenney, C., Almaguer, M., et al.[2022]

Deep brain stimulation of the anterior nuclei of the thalamus (ANT-DBS) has shown promising results in reducing seizure frequency in patients with focal epilepsy, with reductions of 41% at 1 year, 69% at 5 years, and 75% at 7 years.

While ANT-DBS can lead to non-serious adverse effects like depression and memory impairment, the long-term benefits in seizure control suggest it is a viable treatment option, although further large-scale studies are needed to optimize therapy and identify predictors of success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the anterior nuclei of the thalamus in focal epilepsy. Deutschová, B., Rektor, I.[2023]

In a patient with MS-related tremor, simultaneous stimulation of multiple thalamic targets (V.im. and V.o.a.) did not provide additional benefits compared to stimulating each target individually, indicating that more complex stimulation may not always lead to better outcomes.

For a patient with poststroke Holmes' tremor, stimulation of the globus pallidus internus (Gpi) was effective in reducing tremors, suggesting that targeting this area can be a viable alternative to thalamic stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple target deep brain stimulation for multiple sclerosis related and poststroke Holmes' tremor. Lim, DA., Khandhar, SM., Heath, S., et al.[2022]

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) significantly improves tremor and handwriting in patients with essential tremor, with an average tremor score reduction from 3.27 to 0.64 and handwriting score from 2.94 to 0.89 over an average follow-up of 56.9 months.

The treatment is considered safe, with an 80.4% improvement in tremor and 69.7% in handwriting, although some patients may experience tolerance requiring adjustments in stimulation parameters, and the overall hardware-related complication rate was 23.5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of thalamic deep brain stimulation for essential tremor. Zhang, K., Bhatia, S., Oh, MY., et al.[2022]

Deep brain stimulation (DBS) of the ventral intermediate (Vim) thalamic nucleus is an effective treatment for tremor disorders, particularly essential tremor and tremor-dominant Parkinson's disease.

There are technical variations in the surgical techniques used for Vim DBS, particularly in preoperative imaging and electrode trajectory planning, which can influence the procedure's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical Technique of Ventral Intermediate Thalamic Deep Brain Stimulation]. Morishita, T., Tanaka, H., Inoue, T.[2021]

Deep brain stimulation (DBS) of the thalamic ventral-intermediate nucleus (VIM) is a safe and effective treatment for tremors associated with multiple sclerosis (MS), showing up to 61% improvement in tremor scores at 6 months post-surgery in a study of 7 patients.

Patients experienced significant enhancements in their quality of life, with improvements ranging from 30% to 175% at 6 months, and these benefits were sustained for an average follow-up of 26.6 months, indicating long-term efficacy of the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection and outcome of deep brain stimulation for multiple sclerosis-associated tremor. Paranathala, MP., Mills, R., Rai, P., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality. [2021]

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

Dual electrode thalamic deep brain stimulation for the treatment of posttraumatic and multiple sclerosis tremor. [2006]

3. Germany pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation of thalamus for tremor control]. [2009]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for posttraumatic action tremor. [2009]

5. England pubmed.ncbi.nlm.nih.gov

Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Long term safety and efficacy of unilateral deep brain stimulation of the thalamus for parkinsonian tremor. [2019]

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

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. [2022]

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

Long-term evaluation of deep brain stimulation of the thalamus. [2022]

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

Hyperhidrosis due to deep brain stimulation in a patient with essential tremor. Case report. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the anterior nuclei of the thalamus in focal epilepsy. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Multiple target deep brain stimulation for multiple sclerosis related and poststroke Holmes' tremor. [2022]

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

Long-term results of thalamic deep brain stimulation for essential tremor. [2022]

13. Japan pubmed.ncbi.nlm.nih.gov

[Surgical Technique of Ventral Intermediate Thalamic Deep Brain Stimulation]. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Patient selection and outcome of deep brain stimulation for multiple sclerosis-associated tremor. [2023]