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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NEPTUNE to help people recover cognitive abilities after a stroke. The focus is on repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain therapy that uses magnetic fields to boost brain activity. Participants will undergo eight short sessions over three days to determine if this treatment can safely improve brain function. Ideal candidates are those who have experienced a stroke on the right side of their brain in the past six months and can perform certain cognitive tasks. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for stroke recovery.

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 prior data suggests that this rTMS protocol is safe for post-stroke rehabilitation?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for aiding stroke recovery. Studies have found that rTMS can improve various stroke symptoms, although it might not work for everyone. A specific type of rTMS, theta burst stimulation (TBS), used in the NEPTUNE treatment, has shown benefits in stroke recovery.

Most people tolerate these treatments well, experiencing only mild side effects like slight headaches or tingling on the scalp, which usually resolve quickly. So far, studies have not found strong evidence of serious safety concerns.

The NEPTUNE study aims to further explore the safety of this treatment and its potential to improve thinking skills and brain function after a stroke. This information can help prospective trial participants understand what to expect from the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for stroke rehabilitation focus on physical therapy and medications to prevent further strokes or complications. But NEPTUNE is unique because it uses a cutting-edge technique called intermittent theta burst repetitive transcranial magnetic stimulation (iTBS). This non-invasive brain stimulation targets the left dorsolateral prefrontal cortex, a brain area crucial for cognitive and motor recovery. Researchers are excited because NEPTUNE's approach could potentially speed up recovery by enhancing brain plasticity, offering quicker and possibly more effective results compared to traditional therapies.

What evidence suggests that this brain stimulation treatment could be effective for post-stroke cognitive problems?

Research has shown that theta burst stimulation (TBS) can help stroke patients regain motor skills. Studies have found that intermittent theta burst stimulation (iTBS), a type of TBS, improves movement and daily activities by enhancing the brain's ability to change and reorganize itself. TBS may surpass traditional brain stimulation methods in effectiveness for stroke recovery. In this trial, participants will receive the NEPTUNE treatment, which employs a high-dose TBS approach. These findings suggest that NEPTUNE could also enhance cognitive skills in stroke survivors. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/brain-stimulation-for-stroke-83f2e

Brain Stimulation for Stroke (NEPTUNE Trial) Early sensory stimulation within the first 6 hours after an ischemic stroke may have significant effects on recovery, with preclinical studies showing both ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11605871/

The effectiveness of theta burst stimulation for motor recovery ... Our results show that TBS has a good effect on improving motor function in stroke patients, but more large-scale, high-quality, multicenter ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05613686

NCT05613686 | Theta Burst Stimulation for Motor Recovery This study will compare efficacy of different doses iTBS in combination with inhibitory rTMS on motor recovery and cortical excitability in subacute stroke ...

4. bmcneurol.biomedcentral.com bmcneurol.biomedcentral.com/articles/10.1186/s12883-023-03492-0

Theta burst stimulation: what role does it play in stroke ... Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9298981/

The Effectiveness of Intermittent Theta Burst Stimulation for ... Our study established the efficacy of iTBS in improving motor cortical plasticity, motor function, and daily functioning in stroke patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6763938/

Repetitive transcranial magnetic stimulation in stroke ... The current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05613686

NCT05613686 | Theta Burst Stimulation for Motor Recovery This study will compare efficacy of different doses iTBS in combination with inhibitory rTMS on motor recovery and cortical excitability in subacute stroke ...