Thalamic Stimulation for Temporal Lobe Epilepsy

(START Trial)

Not currently recruiting at 2 trial locations

Overseen By Kristine DaCosta

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Antiseizure medications

Must not be taking: Anticoagulants, Aspirin

Disqualifiers: Substance abuse, Personality disorders, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for individuals with temporal lobe epilepsy, particularly when current treatments fail to stop seizures. Rather than stopping seizures, the study employs thalamic stimulation (a type of brain stimulation) to help patients regain consciousness during a seizure. This method could significantly benefit those whose seizures affect awareness and who find no relief with other treatments. Ideal participants have temporal lobe epilepsy, experience at least two disabling seizures a month that impact daily life, and have not improved with medication. As an unphased trial, this study provides a unique opportunity for patients to contribute to groundbreaking research that could transform epilepsy treatment.

Will I have to stop taking my current medications?

The trial requires participants to stay on their current antiseizure medications, but dose adjustments are allowed within accepted therapeutic ranges. Short-term use of benzodiazepines is also permitted for acute seizure worsening.

What prior data suggests that central thalamic stimulation is safe for temporal lobe epilepsy patients?

Research has shown that thalamic stimulation is safe and effective in treating epilepsy. In one study, 17 out of 24 participants who received this treatment for at least six months experienced a significant reduction in seizures, with more than half showing substantial improvement. This indicates the treatment is generally well-tolerated.

Another review found that stimulating the thalamus led to a 64% to 69% reduction in seizures, depending on the specific area targeted. This reduction suggests promise for patients with difficult-to-control epilepsy.

These studies indicate that thalamic stimulation may be a safe option for people with epilepsy. However, individual experiences can vary, so discussing options with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Central Thalamic Stimulation for temporal lobe epilepsy because it offers a novel approach by directly targeting the thalamus, a brain region involved in seizure activity, with electrical stimulation. Unlike traditional treatments like anti-seizure medications that focus on altering chemical signals in the brain, this method uses a neurostimulator device to deliver precise electrical impulses, potentially reducing seizure duration and frequency more effectively. Additionally, this technique provides a customized therapy by adapting stimulation levels based on the patient's specific needs, which could lead to better seizure control with fewer side effects compared to current standard care options.

What evidence suggests that central thalamic stimulation might be an effective treatment for temporal lobe epilepsy?

This trial will compare therapeutic thalamic stimulation with non-therapeutic (sham) stimulation for temporal lobe epilepsy. Research has shown that stimulating the central thalamus might help individuals with temporal lobe epilepsy become more aware during seizures. Previous studies found that this method can alter brain connectivity, potentially aiding consciousness during seizures. This treatment targets a brain area crucial for wakefulness and alertness. Evidence from similar research suggests this approach could also benefit other seizure types or brain conditions affecting awareness. Although more research is needed, these early results offer promise for those unable to control seizures with other treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Barbara Jobst, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Gregory Worrell, MD, PhD

Principal Investigator

Mayo Clinic

Hal Blumenfeld, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with temporal lobe epilepsy not controlled by medication, surgery, or other neurostimulation. Candidates must have a history of mesial temporal seizures, be drug-resistant to at least two antiseizure medications, and be medically stable. They should also be able to complete neuropsychology evaluations and manage the stimulation device.

Inclusion Criteria

I have tried at least two seizure medications without success.

Ability and willingness to provide informed consent and participate in the study protocol

I have epilepsy with at least 2 severe seizures a month.

Exclusion Criteria

I have a condition or take medication that affects how my blood clots.

I am on blood thinners and cannot stop them for surgery.

I have been diagnosed with seizures not caused by epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation

Neurostimulator device is implanted and initial setup is performed

4 weeks

1 visit (in-person)

Therapeutic Thalamic Stimulation

Patients receive hippocampal and thalamic stimulation for seizures longer than five seconds

4 months

Regular in-person visits for monitoring and adjustment

Non-Therapeutic Thalamic Stimulation

Patients receive hippocampal stimulation and sub-therapeutic thalamic stimulation for control

4 months

Regular in-person visits for monitoring and adjustment

Optional Randomized CL Stimulation

Patients may participate in an additional phase with randomized CL stimulation if no benefit is experienced

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Central Thalamic Stimulation

Trial Overview The study tests whether central thalamic stimulation can restore consciousness during seizures in patients with temporal lobe epilepsy when other treatments fail. It's an innovative approach that differs from previous methods which focus on stopping seizures altogether.

How Is the Trial Designed?

Group I: Therapeutic Thalamic Stimulation Experimental Treatment 2 Interventions

Four months post implant, the neurostimulator device will provide patients with hippocampal stimulation for all seizures. For seizures longer than five seconds, thalamic stimulation will be administered at a therapeutic level established based on the physician's evaluation and patient specific parameters established at a previous visit. This will occur in half of the seizures the patient experiences and will be randomly assigned during this phase of the study. If no benefit is experienced during this phase of the study, patients may participate in an optional randomized CL stimulation phase for an additional four months.

Group II: Non-Therapeutic Thalamic Stimulation Placebo Group 1 Intervention

Four months post implant, the neurostimulator device will provide patients with hippocampal stimulation for all seizures. For seizures longer than five seconds, thalamic stimulation will be administered at below therapeutic threshold to control for implant and placebo effects. This will occur in half of the seizures the patient experiences and will be randomly assigned during this phase of the study. If no benefit is experienced during this phase of the study, patients may participate in an optional randomized CL stimulation phase for an additional four months.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Dartmouth-Hitchcock Medical Center

Collaborator

Trials

548

Recruited

2,545,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04897776

Stimulation of the Thalamus for Arousal Restoral in ... Importantly, previous approaches aim to stop seizures, whereas this study aims to use thalamic stimulation to improve a major negative consequence when seizures ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10942513/

Thalamic stimulation induced changes in network connectivity ... This study leverages single pulse and high frequency thalamic stimulation during stereotactic electroencephalography to assess seizure network engagement.

3. withpower.com withpower.com/trial/phase-epilepsy-8-2021-40f4d

Thalamic Stimulation for Temporal Lobe Epilepsy · Info ... Trial Overview The study tests whether central thalamic stimulation can restore consciousness during seizures in patients with temporal lobe epilepsy when other ...

4. medrxiv.org medrxiv.org/content/10.1101/2025.09.18.25335682v1.full-text

Stimulation of the Thalamus for Arousal Restoral in ... The START clinical trial examined the efficacy and safety of bilateral thalamic CL stimulation to restore consciousness during seizures in TLE ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0969996123000591

Deep brain stimulation of thalamus for epilepsy Efficacy was best documented for focal onset seizures in temporal or frontal lobe. CM stimulation may be useful for generalized or multifocal seizures and PULV ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4352097/

Long-term efficacy and safety of thalamic stimulation for ... The median reduction for temporal lobe seizures was 44% at 1 year (n = 59, p < 0.001) and 76% at 5 years (n = 33, p < 0.001), and 53% at 1 year (n = 25, p = ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0920121125001081

Deep brain stimulation for epilepsy: A systematic review ... Overall seizure reduction was 64.28 % for the anterior nucleus (ANT) and 69.11 %for the centromedian nucleus (CMN). •. Overall responder rates were 61.51 % for ...

8. nature.com nature.com/articles/s43856-025-00920-9

Inter-seizure variability in thalamic recruitment and its ... Thalamic stimulation is a promising approach to controlling seizures in patients with intractable epilepsy. It does not, however, ...

9. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2022.910345/full

Responsive Thalamic Neurostimulation: A Systematic ... Of the subjects who received responsive thalamic stimulation for ≥6 months, 17/24 subjects experienced greater than or equal to 50% reduction, ...