Notice Number: NOT-OD-18-195
Release Date: June 20, 2018
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)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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 Institute on Minority Health and Health Disparities (NIMHD)
National Center for Advancing Translational Sciences (NCATS)
The purpose of this Notice is to solicit administrative supplement applications to existing awards that are currently focused on Down syndrome research in order to accelerate scientific progress to meet new NIH Down syndrome research objectives, as described below. Please see NOT-IC-18-194 for a companion notice for applications that are NOT currently focused on Down syndrome.
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.
This notice initiates a new trans-NIH program 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, immune system dysregulation, 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. Opportunities to engage the Down syndrome community in research are also facilitated by the members of the Down Syndrome Consortium, a public-private partnership involving NIH Institutes and Centers, advocacy groups, private foundations and professional organizations, and self-advocates and families, all sharing a passion for promoting research that will benefit people with Down syndrome.
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 and that are likely to translate into new therapeutic approaches. 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 research that will inform the other two components of the INCLUDE project, namely a cohort study and/or 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 Down syndrome cohort or module in a currently funded trial. Of particular interest are ongoing clinical trials testing therapies for common conditions such as asthma or sleep apnea that occur in people with and without Down syndrome.
We encourage projects that:
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, but 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).
If the parent award is not focused on Down syndrome, see NOT-OD-18-194.
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 to discuss whether the proposed supplement is within the scope of the INCLUDE Project and the priorities of the IC supporting the parent award or with any questions.
Award Project Period
To be eligible, the parent award must receive funds in FY18 (Oct. 1, 2017-Sept. 30, 2018) and is not in an extension period. The request is for one year of funding, but the research proposed in the supplement must be accomplished within 1-2 years. The earliest anticipated start date is August 1, 2018.
Supplement budget requests cannot exceed $500,000 in direct costs exclusive of Facilities and Administrative costs on sub-contracts, or 50% of the direct costs of the current parent award, whichever is less. Requests must reflect the actual needs of the proposed project. Requests may be for one year of support only. 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
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.
As part of the application investigators should submit a no more than one-page abstract of the proposed research that shows the relevance to the INCLUDE project and articulates the component(s) and any IC-specific priorities that the supplement is addressing. Applicants should begin the supplement application abstract by stating: “This application is being submitted to PA-18-591 in accordance with NOT-OD-18-195"
Page Limits: NIH will consider supplements with a Research Strategy of no more than 6 pages, in addition to the abstract.
Supplements should be submitted electronically if allowed by parent mechanism. 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 FOA in order to facilitate efficient processing of the request.
Requests must be received by 5:00 PM Pacific Daylight Time (P.D.T.) on July 23, 2018 for funding in FY 2018.
Institute, Center (IC) and Office-specific Instructions
National Cancer Institute (NCI): NCI priorities include the following:
National Eye Institute (NEI):
The NEI is interested in supplementing existing grants that have the potential to further the understanding of ocular pathologies frequently seen in Down syndrome (manifestations that include, but are not limited to, cataract, amblyopia, strabismus and refractive errors). Applications examining the regulation or dysregulation of eye development in Down syndrome are also encouraged. Interested applicants are advised to contact the NEI program officer prior to submitting the supplement application.
National Heart, Lung, and Blood Institute (NHLBI): NHLBI priorities include the following:
National Human Genome Research Institute (NHGRI): NHGRI is interested in the following:
National Institute on Aging (NIA): NIA is interested in the following:
National Institute of Allergy and Infectious Diseases (NIAID):
Addition of research focused on immune system dysregulation in Down syndrome; its molecular basis, impact on health, including infections and autoimmunity, and intervention strategies.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD priorities include:
National Institute on Deafness and Other Communication Disorders (NIDCD): NIDCD priorities include:
National Institute of Dental and Craniofacial Research (NIDCR):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
NIDDK is interested in research focused on Down syndrome and obesity, urologic conditions, type 1 diabetes, autoimmune thyroid disease, and other autoimmune diseases within the purview of NIDDK.
National Institute of Environmental Health Sciences (NIEHS):
The PD/PI must propose a project that has a focus on environmental exposures within the NIEHS mission. Environmental agents which are considered of primary interest for NIEHS include: industrial chemicals or manufacturing byproducts, metals, pesticides, herbicides, air pollutants and other inhaled toxicants, particulates or fibers, fungal, and bacterial or biologically derived toxins. Investigators who propose studies with a primary focus on NIEHS mission-relevant exposures are encouraged to consider inclusion of other relevant environmental exposures (e.g., periconceptional smoking) in order to assess their role(s) as cofactors/modifiers of the risk or protection associated with the primary exposure(s). Applications that propose laboratory-based studies using only model compounds (i.e., those without potential for human exposure) must provide a clear, reasonable and specific description as to how research on the model compound will lead to a better understanding of the mechanisms involved in responses to specific environmental agents which are included in the mission responsibility of the NIEHS.
NIEHS priorities include the following:
National Institute of General Medical Sciences (NIGMS):
As the NIGMS MIRA (Maximizing Investigators’ Research Award) program provides support for an investigator's overall program of research within the Institute’s mission, MIRA awardees are not eligible for this supplement program.
National Institute of Neurological Disorders and Stroke (NINDS): NINDS priorities include the following:
National Institute of Nursing Research (NINR):
NINR priorities for research on co-occurring conditions across the lifespan of individuals with Down syndrome include health promotion, disease prevention, health disparities, caregiving, management of symptoms, self-management, genetics, epigenetics, palliative care needs and care at the end of life. Topics of special interest include integration of biological and behavioral sciences, application of new technologies to research questions, and improving the quality and effectiveness of interventions.
National Institute on Minority Health and Health Disparities (NIMHD):
NIMHD priorities include the inclusion of individuals with Down syndrome from NIH-designated health disparity populations (Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asians, Native Hawaiians and Other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities) into existing clinical or community-based studies in sufficient number to conduct meaningful subgroup analysis.
Topics of particular interest related to individuals with Down syndrome from health disparity populations include but are not limited to the following:
Each IC will conduct administrative reviews of applications submitted to their IC separately. The NIH Office of the Director will make funds available for the top applications submitted for consideration for this cross-IC program.
1. Is the work proposed within the scope of the active award?
2. Are the work proposed and the parent award focused on Down syndrome research?
3. Does the work proposed address one of the components listed under the Down syndrome research objectives?
4. Does the work proposed have scientific merit?
5. Is the work likely to stimulate additional activity leading to progress on Down syndrome?
6. Does the work address a priority for the IC that issued the parent award (if applicable)?
Please direct all inquiries to the contact at the Institute, Center or Office supporting the parent award:
Melissa A. Parisi, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Anna E. Mazzucco, PhD
National Institutes of Health (NIH )
Malcolm A. Smith, MD, PhD
National Cancer Institute (NCI )
Houmam Araj, PhD
National Eye Institute (NEI )
Charlene Schramm, PhD
National Heart, Lung, and Blood Institute (NHLBI )
Joy T. Boyer, BA
National Human Genome Research Institute (NHGRI )
Laurie M. Ryan, PhD
National Institute on Aging (NIA )
Frosso Voulgaropoulou, PhD
National Institute of Allergy and Infectious Diseases (NIAID )
Lana Shekim, PhD
National Institute on Deafness and Other Communication Disorders (NIDCD )
Jason Wan, PhD
National Institute of Dental and Craniofacial Research (NIDCR )
Ellen Leschek, PhD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK )
Jonathan A. Hollander, PhD
National Institute of Environmental Health Sciences (NIEHS )
Robert Riddle, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS )
Rebekah S. Rasooly, PhD
National Institute of Nursing Research (NINR )
Nathan Stinson, Jr., PhD, MD
National Institute on Minority Health and Health Disparities (NIMHD )