Epilepsy, Temporal LobeSTARTNCT04897776
Stimulation of the Thalamus for Arousal Restoral in Temporal Lobe Epilepsy
A study testing Central Thalamic Stimulation and Hippocampal Stimulation in people with Epilepsy, Temporal Lobe, run by Yale University at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Epilepsy, Temporal Lobe
- What is being tested?
- Central Thalamic Stimulation and Hippocampal Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- 31 Oct 2021to 15 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients will have evidence of mesial temporal seizures based on either
- Intracranial EEG monitoring with mesial temporal lobe onset
- or scalp EEG evidence of temporal lobe seizures and other evidence of mesial temporal lobe epilepsy.
- 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.
- 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.
- 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.
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- Drug resistance to at least two antiseizure medications (ASM) with adequate dose and duration.
- 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.
- 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.
- The local treating epilepsy center has recommended the patient for brain stimulation therapy on clinical grounds and without reference to this protocol.
- Age 18 to 75 years, inclusive, at time of consent.
- Ability and willingness to provide informed consent and participate in the study protocol.
- 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.
- Subject has seizures that are distinct, stereotypical events that can be reliably counted by the patient or caregiver.
- Subject can reasonably be expected to maintain a seizure diary alone or with the assistance of a competent individual.
- Subject can complete regular office visits and telephone appointments in accordance with the study protocol requirements.
- 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.
- 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.
- Subject speaks and reads English.
- Subject's anatomy will permit implantation of the Medtronic Investigational Summit RC+S generator within 20 mm of the skin surface.
- 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.
Who cannot join
- Subject has a contraindication to magnetic resonance imaging.
- Subject has a significant substance abuse history (alcohol, prescription, or illicit medications) within the preceding two years with evidence of impact on daily function.
- Subject participated in another drug or device trial within the preceding 30 days.
- 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.
- Suicide attempt in the past year.
- Arrest for assault or possession of drugs or weapons with intent to sell/distribute in the past year.
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- 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.
- Subject has confirmed active diagnosis of psychogenic or non-epileptic seizures.
- Subject has confirmed diagnosis of primary generalized seizures.
- Subject has experienced unprovoked status epilepticus in the preceding year.
- Subject has had therapeutic surgery to treat epilepsy that may interfere with electrode placement.
- Subject has progressive neurological disorder or medical condition that would prevent the participant to fully participate in the clinical trial.
- Subject has severe chronic pulmonary disease or cardiac disease, local, systemic acute or chronic infectious illness.
- Subject is on anticoagulants and is unable to discontinue them peri-surgically, as required by the neurosurgeon or Investigator.
- 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.
- Subject is ineligible for cranial surgery.
- Subject scores equal to or below a full-scale intelligence quotient (FSIQ) of 70, as measured by the Wechsler Adult Intelligence Scale.
- Pregnancy.
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Yale New Haven Hospital
New Haven, Connecticut, 06510
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Thalamic Stimulation to Prevent Impaired Consciousness in Epilepsy
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.
Read the detailed description
Impaired consciousness during seizures has a major negative impact on quality of life for people with epilepsy. Consequences include risk of motor vehicle accidents, drowning, poor work and school performance, and social stigmatization. Impaired ictal/postictal arousal may also compromise breathing leading to sudden unexpected death in epilepsy. Although the primary goal of epilepsy care is to stop seizures, restoring conscious awareness in patients whose seizures cannot be stopped (by medications, surgery or deep brain stimulation) could significantly improve outcome. Disorders of consciousness other than epilepsy have long been known to arise from dysfunction of subcortical-cortical arousal circuits. Deep brain stimulation (DBS) of the thalamic intralaminar central lateral nuclei (CL) is a promising approach to restore conscious arousal currently being trialed for chronic disorders of consciousness. Recent neuroimaging and EEG studies have shown that transient impaired consciousness in temporal lobe epilepsy (TLE) seizures also depends on subcortical-cortical arousal including thalamic CL. Translational studies from this research group further demonstrate depressed CL function in limbic seizures, and most importantly that thalamic CL stimulation has the potential to restore physiological and behavioral arousal in the ictal and postictal periods. DBS treatment of epilepsy has advanced rapidly with FDA approval of responsive neurostimulation (RNS, NeuroPace) and thalamic anterior nucleus stimulation (Medtronic). Investigational devices such as the Medtronic Summit RC+S provide a unique opportunity for responsive stimulation of up to four separate brain regions, enabling conventional sites such as hippocampus (HC) to be combined with innovative targets such as thalamic CL. Meanwhile, collaborators Mayo Clinic have developed the Epilepsy Personal Assistant Device (EPAD), a custom application running on a hand-held device with bi-directional communication with the RC+S. The EPAD will enable cloud-based data storage, seizure diaries, and automatic behavioral tests. Therefore, the goal is to develop and pilot test the feasibility and safety of bilateral thalamic CL stimulation using RC+S to restore conscious arousal in TLE seizures which are not stopped by conventional responsive neurostimulation, offering hope to greatly improve quality of life in these patients.
- Conditions
- Epilepsy, Temporal Lobe
- Being tested
- Central Thalamic Stimulation, Hippocampal Stimulation
- Keywords
- Thalamic Stimulation, Hippocampal Stimulation, Awareness, Ictal Awareness, Post-ictal Awareness, Consciousness, Temporal Lobe Epilepsy, Epilepsy, Quality of Life, Cognition, Neurostimulation, Deep Brain Stimulation, Responsive Neurostimulation, Intralaminar Thalamus, Thalamic Central Lateral Nucleus, Device, Behavioral Assessment
- Medical subject headings
- Epilepsy, Temporal Lobe, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Central Thalamic StimulationDevice
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 StimulationDevice
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)
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic Thalamic Stimulation | Experimental | 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. Receives: Device: Central Thalamic Stimulation; Device: Hippocampal Stimulation |
| Non-Therapeutic Thalamic Stimulation | Sham comparator | 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. Receives: Device: Hippocampal Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Conscious Awareness
Evaluate levels of conscious awareness during and following seizures, based on a behavioral responsiveness scale. Behavioral responsiveness is delivered on a tablet device automatically when a seizure is identified by the neurostimulator device. Automatic Responsiveness Testing in Epilepsy has a score range of 0 to 18, where 0 is not consciousness and/or unable to interact appropriately to commands and 18 is conscious, aware, and able to interact appropriately to commands. This is measured at scheduled in weekly intervals prior to implant and continuously over the 45 months of participation that occur post-implant.
Measured: Up to 45 months
Secondary outcomes (2)
Change in Seizure Severity
Evaluate changes seizure severity with the Liverpool Seizure Severity Questionnaire. Questionnaires will be given to patients to complete during in-person visits to evaluate changes in reported seizure frequency, which will also be compared to the objective seizure count from the Medtronic Summit RC+S device post-implant. The Liverpool Seizure Severity Scale 2.0 questionnaire produces a single unit-weighted scale that measures severity of the most severe seizures the patient experienced during the recall period. Score ranges are from 0 to 100, where 0 is the patient reports no seizures whereas 100 indicates frequent seizures with severe symptomology, including headaches, confusion, and delays in returning to tasks. Measured at each in-person visit from Baseline to End of Study (13 times over 45 months).
Measured: Up to 45 months
Change in Quality of Life
Evaluate changes quality of life periodically with epilepsy-specific standardized assessment tools. Questionnaire will be given to patients to complete at in-person visits as to evaluate changes in quality of life. Quality of Life in Epilepsy Inventory is converted to a t-score range of 11 to 73, where 11 is a low quality of life with limited independence, low cognitive function, and significant seizure worry whereas a score of 73 indicates high levels of satisfaction in their health, minimal seizure worry, and high social function. Measured at each in-person visit from Baseline to End of Study (13 times over 45 months).
Measured: Up to 45 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start31 Oct 2021
- Primary completion16 Jun 2025
- Study completion15 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Epilepsy, Temporal LobeStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- After controlling for implant effects and hippocampal stimulation, there will be a period of blinding for thalamic stimulation. Physician and patient will not know which seizures during this period receive stimulation or sham stimulation. The primary outcome measure will be comparing behavioral awareness scores during this period, sham stimulation compared to therapeutic stimulation.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Mayo Clinic, Dartmouth-Hitchcock Medical Center, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Hal Blumenfeld, MD, PhD, Yale University
- Investigators
- Hal Blumenfeld, MD, PhD, Principal investigator, Yale UniversityBarbara Jobst, MD, PhD, Principal investigator, Dartmouth-Hitchcock Medical CenterGregory Worrell, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04897776
- Sponsor's protocol ID
- 2000030289
- Other IDs
- 1UG3NS112826-01
- Acronym
- START
- Status last verified
- Nov 2025
- First submitted
- 11 May 2021
- Last updated
- 26 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25200252Geller 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.
PubMed 28398014Salanova 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.
PubMed 25663221Schiff 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.
PubMed 17671503Kremen 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.
PubMed 30310759
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thalamic Stimulation to Prevent Impaired Consciousness in Epilepsy
- ClinicalTrials.gov ID
- NCT04897776
- Acronym / sponsor ID
- START / 2000030289
- Conditions
- Epilepsy, Temporal Lobe
- Keywords
- Thalamic Stimulation, Hippocampal Stimulation, Awareness, Ictal Awareness, Post-ictal Awareness, Consciousness, Temporal Lobe Epilepsy, Epilepsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Mayo Clinic, Dartmouth-Hitchcock Medical Center, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 31 Oct 2021 (actual)
- Primary completion
- 16 Jun 2025 (actual)
- Study completion
- 15 Jul 2025 (actual)
- First posted
- 24 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Impaired consciousness during seizures has a major negative impact on quality of life for people with epilepsy. Consequences include risk of motor vehicle accidents, drowning, poor work and school performance, and social stigmatization. Impaired ictal/postictal arousal may also compromise breathing leading to sudden unexpected death in epilepsy. Although the primary goal of epilepsy care is to stop seizures, restoring conscious awareness in patients whose seizures cannot be stopped (by medications, surgery or deep brain stimulation) could significantly improve outcome. Disorders of consciousness other than epilepsy have long been known to arise from dysfunction of subcortical-cortical arousal circuits. Deep brain stimulation (DBS) of the thalamic intralaminar central lateral nuclei (CL) is a promising approach to restore conscious arousal currently being trialed for chronic disorders of consciousness. Recent neuroimaging and EEG studies have shown that transient impaired consciousness in temporal lobe epilepsy (TLE) seizures also depends on subcortical-cortical arousal including thalamic CL. Translational studies from this research group further demonstrate depressed CL function in limbic seizures, and most importantly that thalamic CL stimulation has the potential to restore physiological and behavioral arousal in the ictal and postictal periods. DBS treatment of epilepsy has advanced rapidly with FDA approval of responsive neurostimulation (RNS, NeuroPace) and thalamic anterior nucleus stimulation (Medtronic). Investigational devices such as the Medtronic Summit RC+S provide a unique opportunity for responsive stimulation of up to four separate brain regions, enabling conventional sites such as hippocampus (HC) to be combined with innovative targets such as thalamic CL. Meanwhile, collaborators Mayo Clinic have developed the Epilepsy Personal Assistant Device (EPAD), a custom application running on a hand-held device with bi-directional communication with the RC+S. The EPAD will enable cloud-based data storage, seizure diaries, and automatic behavioral tests. Therefore, the goal is to develop and pilot test the feasibility and safety of bilateral thalamic CL stimulation using RC+S to restore conscious arousal in TLE seizures which are not stopped by conventional responsive neurostimulation, offering hope to greatly improve quality of life in these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- After controlling for implant effects and hippocampal stimulation, there will be a period of blinding for thalamic stimulation. Physician and patient will not know which seizures during this period receive stimulation or sham stimulation. The primary outcome measure will be comparing behavioral awareness scores during this period, sham stimulation compared to therapeutic stimulation.
| Arm | Type | Receives |
|---|---|---|
| Therapeutic Thalamic Stimulation | Experimental | Device: Central Thalamic Stimulation, Device: Hippocampal StimulationFour 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. |
| Non-Therapeutic Thalamic Stimulation | Sham comparator | Device: Hippocampal StimulationFour 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 may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- All patients will have evidence of mesial temporal seizures based on either
- 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.
- 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.
- Drug resistance to at least two antiseizure medications (ASM) with adequate dose and duration.
- 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.
Key exclusion criteria (19 listed)
- Subject has a contraindication to magnetic resonance imaging.
- Subject has a significant substance abuse history (alcohol, prescription, or illicit medications) within the preceding two years with evidence of impact on daily function.
- Subject participated in another drug or device trial within the preceding 30 days.
- 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.
- Suicide attempt in the past year.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Central Thalamic StimulationStimulation 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. | Device | Therapeutic Thalamic Stimulation |
| Hippocampal StimulationThe 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) | Device | Non-Therapeutic Thalamic Stimulation, Therapeutic Thalamic Stimulation |
Primary outcome
Change in Conscious Awareness
Time frame: Up to 45 months
Evaluate levels of conscious awareness during and following seizures, based on a behavioral responsiveness scale. Behavioral responsiveness is delivered on a tablet device automatically when a seizure is identified by the neurostimulator device. Automatic Responsiveness Testing in Epilepsy has a score range of 0 to 18, where 0 is not consciousness and/or unable to interact appropriately to commands and 18 is conscious, aware, and able to interact appropriately to commands. This is measured at scheduled in weekly intervals prior to implant and continuously over the 45 months of participation that occur post-implant.
2 secondary outcomes
Change in Seizure Severity
Time frame: Up to 45 months
Change in Quality of Life
Time frame: Up to 45 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
- Background: PubMed 25200252Han 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.
- Background: PubMed 28398014Geller 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.
- Background: PubMed 25663221Salanova 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.
- Background: PubMed 17671503Schiff 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.
- Background: PubMed 30310759Kremen 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.
- Mayo Clinic Appointment RequestLink provided by the sponsor.
- Yale University Appointment RequestLink provided by the sponsor.
- Dartmouth-Hitchcock Medical Center Appointment RequestLink provided by the sponsor.
- Individual participant dataSharing planned: No
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A Phase I Clinical Trial of UX-GIP001 in the Treatment of Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy
Epilepsy
RecruitingPhase 3
Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (EPIC (EPIlepsy Cell Therapy))
Mesial Temporal Lobe Epilepsy
RecruitingObservational study
Surgery as a Treatment for Medically Intractable Epilepsy
Epilepsy, Epilepsy, Temporal Lobe
RecruitingObservational study
Investigating Epilepsy: Screening and Evaluation
Seizures, Epilepsy
Recruiting
Overnight TI in TLE
Temporal Lobe Epilepsy (TLE), Drug Resistant Epilepsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hal Blumenfeld, MD, PhD principal investigator
Yale University
Barbara Jobst, MD, PhD principal investigator
Dartmouth-Hitchcock Medical Center
Gregory Worrell, MD, PhD principal investigator
Mayo Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Central Thalamic Stimulation and Hippocampal Stimulation in people with Epilepsy, Temporal Lobe, run by Yale University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Conscious Awareness (time frame: Up to 45 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04897776, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.