Notice of Intent to Publish a Funding Opportunity Announcement for SPARC VNS Endpoints from Standardized Parameters (VESPA) (U54 Clinical Trial Required)
Notice Number:
NOT-RM-22-001

Key Dates

Release Date:
September 29, 2021
Estimated Publication Date of Funding Opportunity Announcement:
January 07, 2022
First Estimated Application Due Date:
April 01, 2022
Earliest Estimated Award Date:
September 16, 2022
Earliest Estimated Start Date:
September 16, 2022
Related Announcements

None

Issued by

Office of Strategic Coordination (Common Fund)

Purpose

The Office of Strategic Coordination (Common Fund) intends to publish a funding opportunity announcement (FOA) to solicit applications for a new initiative of the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program. This initiative is intended to support a large multisite study of the multi-organ effects of vagus nerve stimulation (VNS) in humans. The FOA will utilize the cooperative agreement U54 activity code. The FOA is expected to be published in December 2021 with an expected application due date in Spring 2021 for FY22 funding.

This Notice is being provided for informational purposes to allow potential applicants additional time to develop responsive applications and meaningful collaborations. NIH reserves the right to modify the scope and objectives as described in this Notice. Final scope, objectives, and requirements will be set forth in the published FOA.

Additional information related to the planned FOA is provided below.

Research Initiative Details

Extensive anatomical connections of the vagus nerve suggest that its activation or blockade should produce multi-organ physiological responses. This is confirmed by the broad diversity of documented functional effects in humans and animal models. Implantable vagus nerve stimulation (VNS) devices are currently FDA-approved for epilepsy, treatment-resistant depression, obesity, and upper extremity motor deficits due to stroke. In addition, VNS is under study as a potential treatment for a variety of autoimmune and chronic inflammatory disorders, gastric motor disorders, nausea, obesity, and Substance Use Disorder (SUD) withdrawal. These disparate potential effects of VNS are often studied in isolation, with multi-organ responses rarely measured. Furthermore, varied experimental conditions, stimulation parameters, and device specifications prevent generalization across studies. As a result, the off-target effects of each strategy, which might be “on-target” in other contexts, remain incompletely characterized.

The intent of the VESPA U54 is to examine the multi-organ effects of vagal nerve stimulation in humans, producing a first-of-its-kind data set that will be shared rapidly and broadly. These data will contribute to the optimization of VNS treatment by providing a multi-system view of the nerve’s functional connectivity in humans, filling a critical knowledge gap. It is expected that data will be generated from direct stimulation of the cervical vagus nerve from at least 200 participants. To facilitate comparison across sites, each participant must receive cervical vagus nerve stimulation via an implanted device, although physiological effects of non-invasive vagal stimulators and/or thoracic or abdominal vagus nerve stimulation may be assessed concomitantly. Multidisciplinary clinical teams will be expected to agree on a common set of stimulation protocols as well as physiological/clinical measures to be acquired from each participant at defined time points across at least three systems (for example, gastrointestinal and digestive, cardiovascular, pulmonary, endocrine, immune and inflammatory, excretory, sympathetic nervous activity, etc.). Clinical studies might include acute or chronic assessments, pre-implantation baseline measurements, ongoing measurements from existing VNS users, sub-studies requiring new investigational device exemptions (IDEs), or new basic physiological research studies in humans. Clinical expertise of the proposed teams should be consistent with the outcome measures proposed. Multidisciplinary teams will be strongly encouraged to develop proposals maximizing the range of measured physiological outcomes.

The NIH will use the U54 mechanism to support multiple functional Cores. The Cores will be expected to seamlessly function together to accomplish the goals of the initiative and the SPARC program as follows:

  • Administration Core (1), which will be the prime awardee and perform all coordinating functions to implement the goals and objectives of the U54 cooperative agreement not explicitly assigned to other cores.
  • Clinical Core (1), which will be responsible for harmonizing a common protocol across sites for collection of consistent multisystem endpoints, securing regulatory approval for the study as needed, and managing ongoing oversight. The Clinical core will also coordinate the recruitment of participants for stimulus parameter adjustment, endpoint measurement, and transmitting data from the clinical sites to the Data Core.
  • Data Core (1), which will gather data acquired from the clinical sites and interface with the SPARC Data and Resource Center to make data available for analysis, and eventually, to control access to the data for research purposes. The Data Core will work with the Analysis and Modeling Core to provide data needed for the computation of a real-world effective dose at the nerve.
  • Analysis and Modeling Core (1), which will perform multivariate analysis of the measured endpoints in response to a variety of vagal nerve stimulation parameters, and use appropriate computational and analytic methods to compute the effective dose at the vagus nerve surface for disparate stimulator geometries, programming parameters, and individual participant anatomies. This will enable pooling of endpoint data by the quantitative “mapping” of stimulation effective dose onto a common spatiotemporal coordinate framework.

The VESPA U54 network is an initiative of the NIH Common Fund’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) program. SPARC seeks to accelerate development of therapeutic approaches that modulate electrical activity in peripheral nerves to improve organ function. The Common Fund supports cross-cutting programs expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and high-risk approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Funding Information
Estimated Total Funding

$21M over 3 years

Expected Number of Awards

1 award

Estimated Award Ceiling

$7M total cost per year

Primary Assistance Listing Number(s)

93.310

Anticipated Eligible Organizations
Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization
Eligible Agencies of the Federal Government

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Wen Chen Ph.D.

National Center for Complementary and Integrative Medicine

301 451-3989

sparc-v@od.nih.gov


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