Notice of Availability of Administrative Supplements for the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndromE) Project (Administrative Supplement/ Clinical Trial Optional)

Notice Number: NOT-OD-19-087

Key Dates
Release Date: March 27, 2019

Related Announcements

PA-18-591
NOT-OD-19-071
RFA-OD-19-015
RFA-OD-19-016
RFA-OD-19-018

Issued by
National Institutes of Health (NIH)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute (NHGRI)
National Institute on Aging (NIA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of General Medical Sciences (NIGMS)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Nursing Research (NINR)
National Center for Complementary and Integrative Health (NCCIH)
National Center for Advancing Translational Sciences (NCATS)
Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)
Office of Strategic Coordination (Common Fund)

Purpose

The National Institutes of Health Office of the Director announces the opportunity for investigators with relevant active NIH-supported research project grants from the participating Institutes listed above to submit administrative supplement applications for funded projects to meet new NIH Down syndrome research objectives related to the NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project (https://www.nih.gov/include-project). This notice is soliciting administrative supplements for the following mechanisms ONLY: Resource-Related Research Projects (R24), Research Program Projects and Centers (P01, P30, P50) cooperative agreements (U10, U19, U24, U54, UG1, UG3, UL1 ) Resource-Related Research Multi-Component Projects and Centers Cooperative Agreements (U2C), and training programs (T32).

Down syndrome is the most common genetic cause of intellectual disability, the most common autosomal trisomy, and one of the most visible and universally recognized genetic syndromes. Each year there are approximately 5300 babies born in the United States with Down syndrome. Within the past 25 years, the average lifespan for a person with Down syndrome has doubled, from 30 to 60 years. While all people with Down syndrome are connected by the common feature of a complete or partial copy of chromosome 21 (trisomy 21), there are significant physical and cognitive differences among them, indicating that inter-individual variability exists.

With this notice, NIH is continuing support for a program of research on Down syndrome initiated in FY2018 to support research on commonly co-occurring conditions in individuals with Down syndrome that are also seen in the general population, such as Alzheimer’s disease/dementia, autism, cataracts, celiac disease, congenital heart disease and diabetes. This is known as the INCLUDE Project (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Information learned by studying people with Down syndrome will also help us learn about these conditions in people without Down syndrome. Likewise, common complications of aging, such as coronary heart disease and solid cancers, are rarely seen in individuals with Down syndrome; this warrants additional study.

This new research initiative expands many of the research objectives and opportunities previously highlighted in the 2014 Down Syndrome Directions: NIH Research Plan on Down Syndrome. More recent discoveries have enhanced our understanding of chromosome segregation and chromosome silencing, identified certain proteins and neurotropic factors involved in brain development using mouse models, and uncovered the role of interferons in immune dysregulation, each of which have the potential to lead to development of novel therapies for individuals with Down syndrome, as well as broader applications. People with Down syndrome are often excluded from clinical research, such as trials of potentially beneficial drugs and therapeutics that are used to treat the same condition in the general population. There is great value in connecting people with Down syndrome to therapies that could improve their overall health and quality of life. And there is great interest in the Down syndrome community in participating in clinical research, based on experience from NICHD’s “DS-Connect®: The Down Syndrome Registry®,” (https://DSConnect.nih.gov), an online survey tool that introduces individuals with Down syndrome and their families to research opportunities.

A comprehensive clinical cohort study with deep phenotyping and exploration of pan-‘omics will permit identification of biomarkers and outcomes for the co-occurring conditions in Down syndrome. Coupled with development of a clinical trials readiness program, and informed by basic science discoveries, this combination of resources could have a great impact on addressing health disparities that exist for people with Down syndrome and could also lead to the development of therapies to improve outcomes for those with and without the condition.

Supplement applications will be considered eligible for funding if they address one or more of the following components related to the INCLUDE Project research objectives:

Component 1: Targeted, high risk-high reward, basic science studies in Down syndrome: For basic science studies, supplements should target areas of science of highest impact. Topics of emphasis may include: chromosome silencing, immune system dysregulation, epigenetic/metabolomic/transcriptomic profiling in model organisms/iPSCs/brain organoids, development of novel model systems, and development of a molecular atlas for cardiac and other specimens. Supplements could also support projects that will inform the other two components, namely a cohort study and a clinical trials network.

Component 2: Molecular snapshot of Down syndrome through a cohort study: The goal is to add to or expand an existing Down syndrome cohort, with data collected in a shared database using common data elements and building on the DS-Connect® patient registry. Supplements could add comprehensive molecular (i.e., pan-‘omics) analyses to existing Down syndrome cohorts or support existing infrastructure for sample and neuroimaging collection in the Down syndrome population.

Component 3: Inclusive clinical research for individuals with Down syndrome: Supplement requests could leverage existing clinical trials infrastructure to expand or extend an existing DS cohort in a currently funded trial or build component(s) into an existing clinical trials infrastructure that includes Down syndrome but could be expanded to accommodate additional Down syndrome clinical trials in the future.

Applications will be considered eligible for funding if they:

  • Are within the scope of the active parent award
  • Are focused on Down syndrome
  • Propose to address one of the components listed under the Down syndrome research objectives
  • Are likely to stimulate additional activity leading to progress on Down syndrome
  • Address a priority for the IC that issued the parent award (if applicable--see below)

Investigators should submit applications as responses to the parent active administrative supplement PA, “Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)”: https://grants.nih.gov/grants/guide/pa-files/PA-18-591.html

Supplements to existing clinical trials are allowed. The proposed research must be within the scope of the parent clinical trial and the parent clinical trial award must have two or more budget years remaining in the current project period . The addition of a new clinical trial that was not a part of the parent award is not allowed. Supplement requests addressing components 2 or 3 should encourage participants with Down syndrome or their caregivers to register in DS-Connect®: The Down Syndrome Registry (https://DSConnect.nih.gov).

Before submitting a supplement request, principal investigators are strongly encouraged to contact their program officer or the program contact at the Institute, Center or Office supporting the parent award with any questions and to discuss whether the proposed supplement is within the scope of the parent award, focused on the goals of the INCLUDE Project and consistent with the priorities of the IC supporting the parent award.

Award Project Period

To be eligible, the parent award must be active in FY19 (i.e., the parent award received funds in FY19 and is not in an extension period), and the research proposed in the supplement should be requested for 1 year. The awarding institute may consider a no-cost extension of up to an additional year at the conclusion of the first year. The earliest anticipated start date is August 1, 2019.

Budget

Supplement budget requests that exceed $500,000 in direct costs or 50% of the direct costs of the current year of the parent award (exclusive of Facilities and Administrative costs on sub-contracts), must receive permission from the project officer and IC Contact listed below prior to submission.

Requests must reflect the actual needs of the proposed project. Modular and categorical budgets are permitted.

Eligible Individuals (Program Director/Principal Investigator)

Individual(s) must hold an active grant or cooperative agreement. For supplements to parent awards that include multiple PDs/PIs, the supplement may be requested by any or all of the PDs/PIs (in accordance with the existing leadership plan) and submitted by the awardee institution of the parent award.

Submitting an Application

In order to ensure identification, tracking, and appropriate review of their applications, all applicants MUST follow these special instructions

Applications must be submitted electronically through the NIH ASSIST module, an institutional system-to-system (S2S) solution, or Grants.gov Workspace, and must include"NOT-OD-19-087" (without quotation marks) in the Agency Routing Identifier field (Box 4B) of the SF424 R&R form. Applications without this identifier in Box 4B will not be considered for this special initiative. For multi-component awards, the administrative supplements should be prepared as a single project using the FORMS-E-ADMINISUPP RESEARCH project. T32 awards should use FORMS-E-ADMINISUPP TRAINING. In addition, applicants are strongly encouraged to notify the Program contact at the Institute that is supporting the parent award (see list below) that an application has been submitted in response to this Notice in order to facilitate efficient processing of the request.

The application Abstract section should describe the proposed supplement, and the Research Strategy section should include a summary or abstract of the funded parent award or project. The Research Strategy should state the relevance to the parent award and the INCLUDE project, and articulate the component(s) and any IC-specific priorities that the supplement is addressing.

For additional information, see the parent program announcement to Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) PA-18-591.

Page Limits: NIH will consider supplements with a Research Strategy of no more than 6 pages, in addition to the abstract.

Requests must be received by 5:00 PM Pacific Daylight Time (P.D.T.) on May 24 , 2019 for funding in FY 2019.

See Frequently Asked Questions (FAQs) listed on the INCLUDE website for information about specific scientific priorities and program contacts at the NIH participating ICs (https://www.nih.gov/include-project).

Inquiries

Please direct all inquiries to the contact at the Institute, Center or Office supporting the parent award:

Malcolm A. Smith, MD, PhD
National Cancer Institute (NCI)
Telephone: 240-276-6087
Email:Malcolm.Smith@nih.gov

Houmam Araj, PhD
National Eye Institute (NEI)
Telephone: 301-451-2020
Email:arajh@nei.nih.gov

Charlene Schramm, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3793
Email:SchrammC@nhlbi.nih.gov

Joy T. Boyer, BA
National Human Genome Research Institute (NHGRI)
Telephone: 301-480-2247
Email:jb40m@nih.gov

Laurie M. Ryan, PhD
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email:ryanl@mail.nih.gov

Frosso Voulgaropoulou, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3205
Email:fvoulgaropoulou@niaid.nih.gov

Marie Mancini, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: mancinim2@mail.nih.gov

Melissa A. Parisi, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6880
Email: parisima@mail.nih.gov

Kelly King, PhD
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-402-3458
Email: kingke@nidcd.nih.gov

Jonathan A. Hollander, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3269
Email:jonathan.hollander@nih.gov

Donna Krasnewich, MD, PhD
National Institute of General Medical Sciences (NIGMS)
Email: dkras@nigms.nih.gov

Robert Riddle, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5745
Email: rr260c@nih.gov

Rebekah S. Rasooly, PhD
National Institute of Nursing Research (NINR)
Telephone: 301-827-2599
Email:rr185i@nih.gov

Erica Rosemond, Ph.D
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-8927
Email:rosemonde@mail.nih.gov

Robin Boineau, MD, MA
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-435-6286
Email: Robin.Boineau@nih.gov

Sige Zou, PhD
Office of Research Infrastructure Programs (ORIP)
Telephone: 301-435-0749
Email: sige.zou@nih.gov

Concepcion (Marie) Nierras, PhD
Office of Strategic Coordination (Common Fund)
Telephone: 301-435-5840
Email: concepcion.nierras@nih.gov