Brain Stimulation for Stroke

(NEPTUNE Trial)

Overseen By Holly H Fleischmann, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Seizure disorder, Psychotic disorders, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Few treatments are available for post-stroke rehabilitation. The current study aims to develop a novel, short-term, high-dose repetitive transcranial magnetic stimulation (rTMS) based intervention to improve post-stroke cognitive problems. This study will test the safety as well as changes in cognitive function and brain activation with the administration of an accelerated rTMS protocol in chronic 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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment NEPTUNE for stroke?

Research shows that combining nerve stimulation with rehabilitation can help improve motor function and daily activities after a stroke. Additionally, brain stimulation techniques like transcranial magnetic stimulation have shown some promise in improving stroke recovery, although more research is needed to confirm these effects. ^{1 2 3 4 5}

Is brain stimulation for stroke safe for humans?

The safety data for brain stimulation in stroke patients is not directly available in the provided research. However, studies on levetiracetam, a drug sometimes used in brain-related conditions, show it is generally safe and well-tolerated in humans, with common mild side effects like drowsiness and dizziness. Serious side effects are rare and often related to behavior, especially in children or those with a history of behavioral issues. ^{6 7 8 9 10}

How is the NEPTUNE treatment for stroke different from other treatments?

The NEPTUNE treatment for stroke is unique because it involves brain stimulation techniques that modulate specific neural structures to promote recovery. This approach leverages neuroplasticity (the brain's ability to reorganize itself) and may include non-invasive methods like transcranial magnetic stimulation, which are still being explored for their full potential in stroke rehabilitation. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for individuals who have had a stroke in the right hemisphere of their brain within the last 6 months and can perform certain cognitive tasks. They must not have metal implants, history of seizures, severe psychiatric disorders, claustrophobia, substance abuse issues, scalp lesions or wounds, bi-hemispheric strokes or other neurological conditions affecting cognition.

Inclusion Criteria

You do not have any metal implants in your body.

I can complete tasks that require thinking.

I had a stroke in the right side of my brain within the last 6 months.

Exclusion Criteria

I have a history of seizures.

I have had strokes affecting both sides of my brain.

I have had a stroke caused by bleeding in the brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label treatment with rTMS for approximately eight, 3-minute sessions on each of three days within a seven-day span

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and side effects

6 months

Treatment Details

Interventions

• NEPTUNE

Trial Overview The study is testing an accelerated high-dose rTMS protocol to see if it's safe and whether it improves thinking skills and brain activity in people with chronic stroke. rTMS involves using magnetic fields to stimulate nerve cells in the brain.

Participant Groups

Group I: Dose 1 Experimental Treatment 1 Intervention

All participants would receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within a seven-day span. A single session=600 pulses at 120% rMT, iTBS triplets at 50 Hz for 2 s and repeated every 10 s for a total of 190 s to left dlPFC. Total pulses=14,400.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

Early sensory stimulation within the first 6 hours after an ischemic stroke may have significant effects on recovery, with preclinical studies showing both neuroprotective benefits and potential increases in infarct volumes by 30-50%.

Understanding the impact of acute sensory stimulation is crucial, as stroke patients often experience uncontrolled sensory inputs during transport and treatment, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory stimulation in acute stroke therapy. von Bornstädt, D., Gertz, K., Lagumersindez Denis, N., et al.[2023]

Levetiracetam is generally safe and well-tolerated, with common mild-to-moderate side effects like somnolence and dizziness occurring more frequently than in placebo groups, but these usually resolve without needing to stop the medication.

Special populations, including children and those with prior behavioral issues, may experience increased behavioral side effects, but overall, levetiracetam shows a favorable safety profile, with no significant changes in blood chemistry or weight reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levetiracetam safety profiles and tolerability in epilepsy patients. Briggs, DE., French, JA.[2019]

Levetiracetam is an effective antiepileptic drug approved for use in both adults and children (ages 4 and up) for treating partial-onset seizures and juvenile myoclonic epilepsy, with a new intravenous formulation available for cases where oral administration isn't possible.

The drug has an acceptable safety profile, with common side effects like somnolence and dizziness that typically resolve on their own, although serious behavioral side effects may occur more frequently in children and those with a history of behavioral issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of levetiracetam. Sirsi, D., Safdieh, JE.[2019]

In a long-term study involving 55 Japanese children with uncontrolled partial-onset seizures, adjunctive treatment with levetiracetam showed good efficacy, achieving a median seizure reduction of 43.32% and a 50% response rate of 41.8%.

The treatment was generally well-tolerated, with a high incidence of treatment-emergent adverse events (98.2%), but serious adverse drug reactions were rare, indicating that levetiracetam can be a safe option for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of Long-Term Treatment with Levetiracetam as an Adjunctive Therapy in Japanese Children with Uncontrolled Partial-Onset Seizures: A Multicenter, Open-Label Study]. Nakamura, H., Osawa, M., Yokoyama, T., et al.[2022]

References

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

Vagus nerve stimulation paired with rehabilitation for motor function, mental health and activities of daily living after stroke: a systematic review and meta-analysis. [2023]

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

Controversy: Noninvasive and invasive cortical stimulation show efficacy in treating stroke patients. [2022]

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

Sensory stimulation in acute stroke therapy. [2023]

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

Developments in functional electrical stimulation systems. [2016]

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

Nerve Stimulation Enhances Task-Oriented Training in Chronic, Severe Motor Deficit After Stroke: A Randomized Trial. [2018]

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

Levetiracetam safety profiles and tolerability in epilepsy patients. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The safety of levetiracetam. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

[Effects of Long-Term Treatment with Levetiracetam as an Adjunctive Therapy in Japanese Children with Uncontrolled Partial-Onset Seizures: A Multicenter, Open-Label Study]. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events. [2020]

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

Can Children With Perinatal Stroke Use a Simple Brain Computer Interface? [2022]

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

Optimal timing and neural loci: a scoping review on the effect of non-invasive brain stimulation on post-stroke gait and balance recovery. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation for the lower limb after stroke: what do we know so far and what should we be doing next? [2018]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Brain stimulation in poststroke rehabilitation. [2016]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Post-stroke balance rehabilitation under multi-level electrotherapy: a conceptual review. [2020]