Biomarkers to predict outcome from responsive brain stimulation for epilepsy

Ended Project Grant Awarded Last action

Award ID
R61NS125568
Recipient
Awarding agency
Obligated
$11,069,074

Award facts

Completion date
Place of performance
Philadelphia, PA 19104, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The current FDA-approved responsive neurostimulation (RNS) device offers a promising alternative to surgery for more than 600,000 americans with intractable epilepsy who are not candidates for resective surgery. Unfortunately, there are no validated biomarkers to predict seizure outcomes before these devices are placed, and approximately 1/3 of patients do not benefit from RNS long-term. There is a critical need to develop biomarkers based upon clinical and electrophysiological data to determine the most effective therapy for patients with medication-resistant seizures, and to bring quantitative rigor to clinical decision making. The long-term goal of this proposal is to discover and validate a predictive biomarker signature for RNS response that can be used in epilepsy surgery decision making and broadly adopted. To achieve this goal, our overall objective is to develop this prognostic biomarker signature using machine learning applied to a carefully selected set of features and models calculated from intracranial EEG (ieeg) obtained during presurgical evaluation that incorporates qualitative clinical features. We will collaborate across centers and with industry partners via a novel federated approach, whereby each clinical site will post data in a common format to their own, private, cloud-based data store, which will be accessible to analysis pipelines run centrally from our cloud-based platform. Our central hypothesis is that biomarker signatures derived from multimodal data collected during evaluation prior to device implant can be used to predict patient response to RNS therapy. Our preliminary data, analyzing 10 RNS patients each from ucsf, NYU and upenn, demonstrates our ability to perform the proposed research. In the R61 phase, we will test this hypothesis retrospectively in 125 patients who underwent ieeg prior to RNS device placement at the upenn, ucsf and NYU epilepsy centers. Our specific aims for this phase are: 1) to build a federated processing pipeline for biomarker discovery using presurgical evaluation neuroimaging, ieeg and clinical metadata, 2) to identify a predictive biomarker signature from this data. Our federated analysis framework will enable US to: (a) accelerate biomarker discovery across multiple sites and industry partners, (b) satisfy patient and industry limitations on sharing proprietary data, (c) provide a practical framework for rapid adoption across clinical centers worldwide. In the R33 phase, the biomarker signature will be validated in 100 additional patients followed longitudinally at 9 clinical sites. The proposed research is innovative because IT represents a substantive departure from the status QUO by rigorously analyzing multimodal patient data to predict response to RNS and guide decisions on device implantation. The proposed research is significant because IT has the potential to dramatically improve the success rate of RNS for epilepsy through better patient selection. This study also puts into place a novel, versatile, federated data mining infrastructure for multi-center and industry collaboration in translational neuroscience.

Transactions

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Subawards

Subrecipient Amount Awarded
Neuropace Inc. "Dr. Martha Morrell will provide clinical guidance and oversight throughout the project to ensure that the questions being asked of the data are meaningful… $137,638
New York University "For this project, Dr. Friedman will serve as co-Principal Investigator. Along with the co-PIs Drs. Kathryn Davis (contact PI), Vikram Rao, Martha Morrell,… $223,732
The Regents Of The University Of California. San Francisco "This study examines whether electrophysiological biomarkers in intracranial electroencephalography (iEEG) recorded during pre-surgical evaluation of patients… $229,800
Neuropace Inc. Dr. Martha Morrell will provide clinical guidance and oversight throughout the project to ensure that the questions being asked of the data are meaningful… $161,927
The Regents Of The University Of California. San Francisco This study examines whether electrophysiological biomarkers in intracranial electroencephalography (iEEG) recorded during pre-surgical evaluation of patients… $287,249
New York University For this project, Dr. Friedman will serve as co-Principal Investigator. Along with the co-PIs Drs. Kathryn Davis (contact PI), Vikram Rao, Martha Morrell, and… $279,665
Neuropace Inc. Dr. Martha Morrell will provide clinical guidance and oversight throughout the project to ensure that the questions being asked of the data are meaningful… $168,183
New York University For this project, Dr. Friedman will serve as co-Principal Investigator. Along with the co-PIs Drs. Kathryn Davis (contact PI), Vikram Rao, Martha Morrell, and… $330,001

Quick answers

Who received award R61NS125568?

R61NS125568 was awarded to The Trustees Of The University Of Pennsylvania by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on April 1, 2023.

How much is award R61NS125568 worth?

$11,069,074 has been obligated on R61NS125568.

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