Thalamic Stimulation for Temporal Lobe Epilepsy

(START Trial)

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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal is to provide a novel therapeutic option for temporal lobe epilepsy patients when focal impaired awareness seizures cannot be stopped by medications, surgical or laser ablation, or by neurostimulation. The goal is restore consciousness when seizures cannot be stopped. If successful, addition of bilateral thalamic stimulation to existing responsive neurostimulation to rescue consciousness would greatly alter clinical practice and patient outcomes. Importantly, previous approaches aim to stop seizures, whereas this study aims to use thalamic stimulation to improve a major negative consequence when seizures cannot be stopped. The potential impact extends beyond temporal lobe epilepsy to other seizure types, and may also extend more broadly to inform treatment of other brain disorders associated with impaired consciousness and cognition.

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 data supports the effectiveness of the treatment Central Thalamic Stimulation for Temporal Lobe Epilepsy?

Research on thalamic stimulation for epilepsy shows that stimulating the centromedian thalamic nucleus can reduce seizure frequency. In one study, patients experienced a significant decrease in generalized tonic-clonic seizures, and another study reported a 30% reduction in seizure frequency when the stimulator was on. These findings suggest potential benefits of thalamic stimulation for managing seizures. ^{1 2 3 4 5}

Is thalamic stimulation safe for treating epilepsy?

Studies have shown that thalamic stimulation, including stimulation of the anterior and centromedian nuclei, is generally safe and well-tolerated in patients with epilepsy. There were no significant side effects reported, and the treatment was feasible for long-term use. ^{2 6 7 8 9}

How does thalamic stimulation differ from other treatments for temporal lobe epilepsy?

Thalamic stimulation for temporal lobe epilepsy is unique because it involves electrically stimulating specific areas of the thalamus, such as the centromedian nucleus, to control seizures. This approach is different from traditional treatments like antiepileptic drugs, as it directly targets brain activity patterns associated with seizures, offering a potential option for patients who do not respond to medication. ^{1 2 5 10 11}

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

Eligibility Criteria

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.

I am between 18 and 75 years old.

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

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

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

Treatment Details

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.

Participant Groups

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+

References

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

Electrical stimulation of the centromedian thalamic nucleus in control of seizures: long-term studies. [2022]

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

Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Seizure outcome during bilateral, continuous, thalamic centromedian nuclei deep brain stimulation in patients with generalized epilepsy: a prospective, open-label study. [2022]

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

Extratemporal lobe circuits in temporal lobe epilepsy. [2018]

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

Spectral organization of focal seizures within the thalamotemporal network. [2020]

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

Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy. [2022]

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

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. [2022]

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

Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. [2022]

9. Denmark pubmed.ncbi.nlm.nih.gov

Anterior thalamic deep brain stimulation in refractory epilepsy: A randomized, double-blinded study. [2019]

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

Using chronic recordings from a closed-loop neurostimulation system to capture seizures across multiple thalamic nuclei. [2023]

11. Austria pubmed.ncbi.nlm.nih.gov

Role of the centromedian thalamic nucleus in the genesis, propagation and arrest of epileptic activity. An electrophysiological study in man. [2019]