Stimulation of the Thalamus for Arousal Restoral in Temporal Lobe Epilepsy
NCT ID: NCT04897776
Last Updated: 2025-12-26
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
5 participants
INTERVENTIONAL
2021-10-31
2025-07-15
Brief Summary
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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.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
DOUBLE
Study Groups
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Therapeutic Thalamic Stimulation
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.
Central Thalamic Stimulation
Stimulation of the bilateral thalamic CL is a promising approach in human patients to improve conscious arousal. To restore conscious arousal by stimulation of the thalamic intralaminar CL it is necessary to provide bilateral stimulation, placing one lead in each thalamus. Bilateral thalamic CL stimulation was shown previously to improve human conscious arousal and is based on existing research in patients with disorders of consciousness.
Hippocampal Stimulation
The hippocampus has been a target for brain stimulation for seizure reduction in epilepsy. While the efficacy of HC stimulation varies considerably among different studies, the surgical procedure and therapeutic electrical stimulation are well tolerated by patients, with few peri-operative complications being reported, and histopathologic analysis not revealing a difference between stimulated and non-stimulated hippocampal tissue (Han et al. 2014)
Non-Therapeutic Thalamic Stimulation
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.
Hippocampal Stimulation
The hippocampus has been a target for brain stimulation for seizure reduction in epilepsy. While the efficacy of HC stimulation varies considerably among different studies, the surgical procedure and therapeutic electrical stimulation are well tolerated by patients, with few peri-operative complications being reported, and histopathologic analysis not revealing a difference between stimulated and non-stimulated hippocampal tissue (Han et al. 2014)
Interventions
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Central Thalamic Stimulation
Stimulation of the bilateral thalamic CL is a promising approach in human patients to improve conscious arousal. To restore conscious arousal by stimulation of the thalamic intralaminar CL it is necessary to provide bilateral stimulation, placing one lead in each thalamus. Bilateral thalamic CL stimulation was shown previously to improve human conscious arousal and is based on existing research in patients with disorders of consciousness.
Hippocampal Stimulation
The hippocampus has been a target for brain stimulation for seizure reduction in epilepsy. While the efficacy of HC stimulation varies considerably among different studies, the surgical procedure and therapeutic electrical stimulation are well tolerated by patients, with few peri-operative complications being reported, and histopathologic analysis not revealing a difference between stimulated and non-stimulated hippocampal tissue (Han et al. 2014)
Eligibility Criteria
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Inclusion Criteria
1. Intracranial EEG monitoring with mesial temporal lobe onset
2. or scalp EEG evidence of temporal lobe seizures and other evidence of mesial temporal lobe epilepsy.
2. Subject's seizure focus, based upon clinical history, semiology, electroencephalographic (EEG) findings, and/or neuroimaging, shall demonstrate bilateral or unilateral mesial temporal lobe epilepsy, and subject shall not be good candidate for surgical resection.
3. Focal epilepsy with disabling seizure counts mean of ≥ 2 per month. Disabling seizures are those with significant negative impact on the patient's life, involving impaired conscious awareness. Seizures counts will be based on patient's self-report. Note that patient's typically have more disabling seizures than they are able to self-report, and may also have additional non-disabling seizures in addition to the disabling seizures required for enrolment.
i. Mean seizure count ≥ 2 per month is established initially for the preceding 6 months at time of Enrollment, using seizures reported by the patient and/or caregiver. Seizures during EMU admissions are not included.
4. Drug resistance to at least two antiseizure medications (ASM) with adequate dose and duration.
5. Subject is willing to remain on stable ASM from the Baseline phase through the end of the Randomized CL Stimulation phase. Stable is defined as same medications, but dose adjustments are allowed within accepted therapeutic ranges. Also, short-term benzodiazepines allowed for acute seizure worsening as in prior studies.
6. Apart from epilepsy, subject must be medically and neurologically stable and must have no other medical condition in the opinion of the treating physician that would preclude the patient from participation. This could include conditions like severe ischemic cardiac disease, progressive dementia or other disorders that could affect surgical eligibility or compliance.
7. The local treating epilepsy center has recommended the patient for brain stimulation therapy on clinical grounds and without reference to this protocol.
8. Age 18 to 75 years, inclusive, at time of consent.
9. Ability and willingness to provide informed consent and participate in the study protocol.
10. Subject can interpret and to respond, in accordance with the study protocol, to the advisory indicators provided by the device. This includes the ability to recharge the device.
11. Subject has seizures that are distinct, stereotypical events that can be reliably counted by the patient or caregiver.
12. Subject can reasonably be expected to maintain a seizure diary alone or with the assistance of a competent individual.
13. Subject can complete regular office visits and telephone appointments in accordance with the study protocol requirements.
14. A female subject must have a negative pregnancy test and if sexually active, must be using a reliable form of birth control for the duration of the trial, be surgically sterile, or be at least two years post-menopausal.
15. Subject has been informed of his or her eligibility for resective surgery as a potential alternative to the study, if such surgery is a reasonable option.
16. Subject speaks and reads English.
17. Subject's anatomy will permit implantation of the Medtronic Investigational Summit RC+S generator within 20 mm of the skin surface.
18. Subject is capable of completing the proposed neuropsychology evaluation and will score no lower than 2 standard deviations below average on the Wechsler Adult Intelligence Scale.
Exclusion Criteria
2. Subject has a significant substance abuse history (alcohol, prescription, or illicit medications) within the preceding two years with evidence of impact on daily function.
3. Subject participated in another drug or device trial within the preceding 30 days.
4. Demonstrates that they fulfill criteria on any of the three subscale of the SCID-5-PD for borderline, antisocial, or narcissistic personality disorders and these criteria are then corroborated by psychiatric interview, and that this would significantly affect participation in the study.
5. Suicide attempt in the past year.
6. Arrest for assault or possession of drugs or weapons with intent to sell/distribute in the past year.
7. Subject is implanted with pacemaker, implantable cardiac defibrillator, cardiac management product, or a medical device that interferes with the RC+S device. This includes, but is not limited to, direct brain neurostimulators, spinal cord stimulators, vagus nerve stimulators (VNS), and cochlear implants. Patients with a vagus nerve stimulator implanted but turned off through the duration of the study may be enrolled, provided their clinical status has been stable for at least one month with VNS turned off. Alternatively, patients with a VNS may have the previously disabled VNS removed at time of surgery to implant the Medtronic RC+S.
8. Subject has confirmed active diagnosis of psychogenic or non-epileptic seizures.
9. Subject has confirmed diagnosis of primary generalized seizures.
10. Subject has experienced unprovoked status epilepticus in the preceding year.
11. Subject has had therapeutic surgery to treat epilepsy that may interfere with electrode placement.
12. Subject has progressive neurological disorder or medical condition that would prevent the participant to fully participate in the clinical trial.
13. Subject has severe chronic pulmonary disease or cardiac disease, local, systemic acute or chronic infectious illness.
14. Subject is on anticoagulants and is unable to discontinue them peri-surgically, as required by the neurosurgeon or Investigator.
15. Subject has significant platelet dysfunction from medical conditions or medications (including, particularly, aspirin or sodium valproate). If platelet dysfunction is suspected, subject can be enrolled only if a hematologist, the Investigator, and the neurosurgeon judge it to be advisable.
16. Subject is ineligible for cranial surgery.
17. Subject scores equal to or below a full-scale intelligence quotient (FSIQ) of 70, as measured by the Wechsler Adult Intelligence Scale.
18. Pregnancy.
19. Any condition or finding that in the judgement of the site PI significantly increases risk or significantly reduces the likelihood of benefit from participation in the study.
18 Years
75 Years
ALL
No
Sponsors
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Mayo Clinic
OTHER
Dartmouth-Hitchcock Medical Center
OTHER
National Institute of Neurological Disorders and Stroke (NINDS)
NIH
Yale University
OTHER
Responsible Party
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Hal Blumenfeld, MD, PhD
Professor of Neuroscience and of Neurosurgery
Principal Investigators
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Hal Blumenfeld, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Yale University
Barbara Jobst, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Dartmouth-Hitchcock Medical Center
Gregory Worrell, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Mayo Clinic
Locations
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Yale New Haven Hospital
New Haven, Connecticut, United States
Mayo Clinic
Rochester, Minnesota, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Countries
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References
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Han CL, Hu W, Stead M, Zhang T, Zhang JG, Worrell GA, Meng FG. Electrical stimulation of hippocampus for the treatment of refractory temporal lobe epilepsy. Brain Res Bull. 2014 Oct;109:13-21. doi: 10.1016/j.brainresbull.2014.08.007. Epub 2014 Sep 6.
Geller EB, Skarpaas TL, Gross RE, Goodman RR, Barkley GL, Bazil CW, Berg MJ, Bergey GK, Cash SS, Cole AJ, Duckrow RB, Edwards JC, Eisenschenk S, Fessler J, Fountain NB, Goldman AM, Gwinn RP, Heck C, Herekar A, Hirsch LJ, Jobst BC, King-Stephens D, Labar DR, Leiphart JW, Marsh WR, Meador KJ, Mizrahi EM, Murro AM, Nair DR, Noe KH, Park YD, Rutecki PA, Salanova V, Sheth RD, Shields DC, Skidmore C, Smith MC, Spencer DC, Srinivasan S, Tatum W, Van Ness PC, Vossler DG, Wharen RE Jr, Worrell GA, Yoshor D, Zimmerman RS, Cicora K, Sun FT, Morrell MJ. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy. Epilepsia. 2017 Jun;58(6):994-1004. doi: 10.1111/epi.13740. Epub 2017 Apr 11.
Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Troster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25. doi: 10.1212/WNL.0000000000001334. Epub 2015 Feb 6.
Schiff ND, Giacino JT, Kalmar K, Victor JD, Baker K, Gerber M, Fritz B, Eisenberg B, Biondi T, O'Connor J, Kobylarz EJ, Farris S, Machado A, McCagg C, Plum F, Fins JJ, Rezai AR. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007 Aug 2;448(7153):600-3. doi: 10.1038/nature06041.
Kremen V, Brinkmann BH, Kim I, Guragain H, Nasseri M, Magee AL, Pal Attia T, Nejedly P, Sladky V, Nelson N, Chang SY, Herron JA, Adamski T, Baldassano S, Cimbalnik J, Vasoli V, Fehrmann E, Chouinard T, Patterson EE, Litt B, Stead M, Van Gompel J, Sturges BK, Jo HJ, Crowe CM, Denison T, Worrell GA. Integrating Brain Implants With Local and Distributed Computing Devices: A Next Generation Epilepsy Management System. IEEE J Transl Eng Health Med. 2018 Sep 26;6:2500112. doi: 10.1109/JTEHM.2018.2869398. eCollection 2018.
Related Links
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Mayo Clinic Appointment Request
Yale University Appointment Request
Dartmouth-Hitchcock Medical Center Appointment Request
Other Identifiers
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2000030289
Identifier Type: -
Identifier Source: org_study_id