Epilepsy IntractableMEMREINSNCT04286776
Memory Retrieval and Encoding Investigated by Neural Stimulation
A study testing Direct electrical stimulation in people with Epilepsy Intractable, run by University of Pennsylvania at 11 sites in United States.
Trial summary
The purpose of this research is to understand biomarkers of human memory through correlational analyses and to use focal electrical stimulation as a causal manipulation to understand how biomarkers of memory relate to other brain states and behavioral measures. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy Intractable
- What is being tested?
- Direct electrical stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 800 participants
- Where
- 11 sitesUnited States
- Study dates
- 12 Oct 2014to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Expected to undergo intracranial implantation and postoperative electroencephalographic monitoring as part of a standard clinical procedure for the treatment of pharmacologically resistant epilepsy
- Age 18 or older
Who cannot join
- Any physical or cognitive disability or illness that would limit their ability to perform cognitive tasks
- Any medical condition that would, in the investigator's opinion, limit the subject's participation in the study.
- Unable or unwilling to provide informed consent
- MRI contraindications
- Standard clinical care includes a pregnancy test for female patients prior to the surgical implantation of the electrodes. Pregnant women are not surgically implanted.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Emory University Hospital
Atlanta, Georgia, 30322
University of Colorado, Denver
Aurora, Colorado, 80045
National Institute of Neurological Disorders and Stroke
Bethesda, Maryland, 20892
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
UT Southwestern Medical Center
Dallas, Texas, 75390
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
Columbia University
New York, New York, 10027
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Mayo Clinic
Rochester, Minnesota, 55905
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
The purpose of this research is to understand biomarkers of human memory through correlational analyses and to use focal electrical stimulation as a causal manipulation to understand how biomarkers of memory relate to other brain states and behavioral measures.
- Conditions
- Epilepsy Intractable
- Being tested
- Direct electrical stimulation
- Keywords
- episodic memory
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct electrical stimulationDevice
Stimulation will not exceed 0.75 mA and will be approved prior by study investigators. Each subject will have a safety threshold testing at the beginning of each session and if 'afterdischarges' occur the subject's stimulation threshold will be lowered.
| Study group | Role | What they receive |
|---|---|---|
| Direct Electrical Stimulation | Experimental | Stimulation will be applied concurrently with the task, if applicable, and stimulation trials will be interleaved with sham trials, where no stimulation is delivered. Receives: Device: Direct electrical stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory
- We will use linear mixed effects models and L2-penalized logistic regression classifiers to compare periods of successful and unsuccessful performance in our tasks
Measured: Up to 4 weeks (typical duration of hospital stay)
To develop and test models of human brain dynamics in the presence of electrical stimulation
- We will compare spectral indices of brain activity before and after stimulation as a function of stimulation parameters.
Measured: Up to 4 weeks (typical duration of hospital stay)
To assess how reactivation of prior memories shapes subsequent recall and memory organization, including memory for the content, context and value of experiences.
- We will mathematical models of neural similarity described in detail in Halpern (2024) and Manning (2011, 2012) to test the reactivation mechanisms described in Lohnas et al. (2014) and Healey and Kahana (2015).
Measured: Up to 4 weeks (typical duration of hospital stay)
To determine whether state-dependent stimulation can separately be used to modulate encoding and retrieval processes
- We will evaluate the closed-loop stimulation protocol described in Kahana et al. (2023) in both encoding and retrieval.
Measured: Up to 4 weeks (typical duration of hospital stay)
To determine whether stimulation is more effective at modulating memory when targeted to regions with specific connectivity profiles to the medial temporal lobe
- We will compare recall rates during a free recall experiment with brain stimulation at sites with high network-mediated activation, as described in Solomon et al. (2018), versus low network-mediated activation.
Measured: Up to 4 weeks (typical duration of hospital stay)
To determine how simultaneous stimulation at multiple target sites can be optimized to modulate memory
- We will compare recall rates during a free recall experiment with no brain stimulation, stimulation at one site, and stimulation at multiple sites.
Measured: Up to 4 weeks (typical duration of hospital stay)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study start12 Oct 2014
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Epilepsy IntractableStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All enrolled patients are considered eligible to receive direct electrical stimulation. Subjects have the option to receive non stimulation testing only.
- Masking
- None (open label)
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Columbia University
- Responsible party
- Sponsor
- Investigators
- Michael Kahana, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04286776
- Sponsor's protocol ID
- 820553
- Other IDs
- 1U01NS113198-01, 5R01NS106611-05
- Acronym
- MEMREINS
- Status last verified
- Nov 2024
- First submitted
- 24 Feb 2020
- Last updated
- 5 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified data will be shared in a public repository at regular intervals during the project. De-identified data sets will be anonymized prior to posting on the public repository. These de-identified data are likely to be analyzed for secondary purposes other than those described in this protocol (e.g. seizure prediction). Shared data will include, at a minimum, digital spreadsheets used to summarize all participant behavioral data. De-identified electrophysiology data, demographic information, electrode localization information, and task information (e.g. timing of each trial, timing of responses) will be shared in a central repository. Descriptions of the tasks and stimuli will be shared. De-identified references to individual participant data may also appear in scientific journal publications or presented at scientific meetings.
Publications
Ezzyat Y, Kragel JE, Solomon EA, Lega BC, Aronson JP, Jobst BC, Gross RE, Sperling MR, Worrell GA, Sheth SA, Wanda PA, Rizzuto DS, Kahana MJ. Functional and anatomical connectivity predict brain stimulation's mnemonic effects. bioRxiv [Preprint]. 2023 Aug 11:2023.07.27.550851. doi: 10.1101/2023.07.27.550851.
PubMed 37609181Ezzyat Y, Wanda PA, Levy DF, Kadel A, Aka A, Pedisich I, Sperling MR, Sharan AD, Lega BC, Burks A, Gross RE, Inman CS, Jobst BC, Gorenstein MA, Davis KA, Worrell GA, Kucewicz MT, Stein JM, Gorniak R, Das SR, Rizzuto DS, Kahana MJ. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018 Feb 6;9(1):365. doi: 10.1038/s41467-017-02753-0.
PubMed 29410414Kragel JE, Ezzyat Y, Lega BC, Sperling MR, Worrell GA, Gross RE, Jobst BC, Sheth SA, Zaghloul KA, Stein JM, Kahana MJ. Distinct cortical systems reinstate the content and context of episodic memories. Nat Commun. 2021 Jul 21;12(1):4444. doi: 10.1038/s41467-021-24393-1.
PubMed 34290240
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Memory Retrieval and Encoding Investigated by Neural Stimulation
- ClinicalTrials.gov ID
- NCT04286776
- Acronym / sponsor ID
- MEMREINS / 820553
- Conditions
- Epilepsy Intractable
- Keywords
- episodic memory
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Columbia University
- Study start
- 12 Oct 2014 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 27 Feb 2020 (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 purpose of this research is to understand biomarkers of human memory through correlational analyses and to use focal electrical stimulation as a causal manipulation to understand how biomarkers of memory relate to other brain states and behavioral measures.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All enrolled patients are considered eligible to receive direct electrical stimulation. Subjects have the option to receive non stimulation testing only.
| Arm | Type | Receives |
|---|---|---|
| Direct Electrical Stimulation | Experimental | Device: Direct electrical stimulationStimulation will be applied concurrently with the task, if applicable, and stimulation trials will be interleaved with sham trials, where no stimulation is delivered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Expected to undergo intracranial implantation and postoperative electroencephalographic monitoring as part of a standard clinical procedure for the treatment of pharmacologically resistant epilepsy
- Age 18 or older
Key exclusion criteria (5 listed)
- Any physical or cognitive disability or illness that would limit their ability to perform cognitive tasks
- Any medical condition that would, in the investigator's opinion, limit the subject's participation in the study.
- Unable or unwilling to provide informed consent
- MRI contraindications
- Standard clinical care includes a pregnancy test for female patients prior to the surgical implantation of the electrodes. Pregnant women are not surgically implanted.
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 |
|---|---|---|
| Direct electrical stimulationStimulation will not exceed 0.75 mA and will be approved prior by study investigators. Each subject will have a safety threshold testing at the beginning of each session and if 'afterdischarges' occur the subject's stimulation threshold will be lowered. | Device | Direct Electrical Stimulation |
Primary outcome
To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory
Time frame: Up to 4 weeks (typical duration of hospital stay)
1. We will use linear mixed effects models and L2-penalized logistic regression classifiers to compare periods of successful and unsuccessful performance in our tasks
To develop and test models of human brain dynamics in the presence of electrical stimulation
Time frame: Up to 4 weeks (typical duration of hospital stay)
2. We will compare spectral indices of brain activity before and after stimulation as a function of stimulation parameters.
To assess how reactivation of prior memories shapes subsequent recall and memory organization, including memory for the content, context and value of experiences.
Time frame: Up to 4 weeks (typical duration of hospital stay)
3. We will mathematical models of neural similarity described in detail in Halpern (2024) and Manning (2011, 2012) to test the reactivation mechanisms described in Lohnas et al. (2014) and Healey and Kahana (2015).
To determine whether state-dependent stimulation can separately be used to modulate encoding and retrieval processes
Time frame: Up to 4 weeks (typical duration of hospital stay)
4. We will evaluate the closed-loop stimulation protocol described in Kahana et al. (2023) in both encoding and retrieval.
To determine whether stimulation is more effective at modulating memory when targeted to regions with specific connectivity profiles to the medial temporal lobe
Time frame: Up to 4 weeks (typical duration of hospital stay)
5. We will compare recall rates during a free recall experiment with brain stimulation at sites with high network-mediated activation, as described in Solomon et al. (2018), versus low network-mediated activation.
To determine how simultaneous stimulation at multiple target sites can be optimized to modulate memory
Time frame: Up to 4 weeks (typical duration of hospital stay)
6. We will compare recall rates during a free recall experiment with no brain stimulation, stimulation at one site, and stimulation at multiple sites.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- Background: PubMed 37609181Ezzyat Y, Kragel JE, Solomon EA, Lega BC, Aronson JP, Jobst BC, Gross RE, Sperling MR, Worrell GA, Sheth SA, Wanda PA, Rizzuto DS, Kahana MJ. Functional and anatomical connectivity predict brain stimulation's mnemonic effects. bioRxiv [Preprint]. 2023 Aug 11:2023.07.27.550851. doi: 10.1101/2023.07.27.550851.
- Background: PubMed 29410414Ezzyat Y, Wanda PA, Levy DF, Kadel A, Aka A, Pedisich I, Sperling MR, Sharan AD, Lega BC, Burks A, Gross RE, Inman CS, Jobst BC, Gorenstein MA, Davis KA, Worrell GA, Kucewicz MT, Stein JM, Gorniak R, Das SR, Rizzuto DS, Kahana MJ. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun. 2018 Feb 6;9(1):365. doi: 10.1038/s41467-017-02753-0.
- Background: PubMed 34290240Kragel JE, Ezzyat Y, Lega BC, Sperling MR, Worrell GA, Gross RE, Jobst BC, Sheth SA, Zaghloul KA, Stein JM, Kahana MJ. Distinct cortical systems reinstate the content and context of episodic memories. Nat Commun. 2021 Jul 21;12(1):4444. doi: 10.1038/s41467-021-24393-1.
- Individual participant dataSharing planned: Yes. De-identified data will be shared in a public repository at regular intervals during the project. De-identified data sets will be anonymized prior to posting on the public repository. These de-identified data are likely to be analyzed for secondary purposes other than those described in this protocol (e.g. seizure prediction). Shared data will include, at a minimum, digital spreadsheets used to summarize all participant behavioral data. De-identified electrophysiology data, demographic information, electrode localization information, and task information (e.g. timing of each trial, timing of responses) will be shared in a central repository. Descriptions of the tasks and stimuli will be shared. De-identified references to individual participant data may also appear in scientific journal publications or presented at scientific meetings.
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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.
Michael Kahana, PhD principal investigator
University of Pennsylvania
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Direct electrical stimulation in people with Epilepsy Intractable, run by University of Pennsylvania at 11 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 2 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 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. 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?
This study is still under way. Results are not available in the source record yet.
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?
To use direct electrical stimulation to disentangle causal versus correlative biomarkers of verbal and spatial episodic memory (time frame: Up to 4 weeks (typical duration of hospital stay)). The study lists 6 primary outcomes in all. 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 NCT04286776, which also lists 3 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 5 Nov 2024.