The Leona M. and Harry B. Helmsley Charitable Trust’s (Helmsley) Type 1 Diabetes (T1D) Program is launching a Request for Proposals (RFP) to support the development of novel, real-world solutions to help people with T1D exercise safely and to improve their quality of life. Researchers and clinicians are expected to partner with statistical teams to analyze the real-world data that was collected under Helmsley’s T1D Exercise Initiative (T1-DEXI), build collaborations with other necessary third parties, and to test their novel solutions in studies with people with T1D. The overarching purpose of this initiative is to move real-world data towards real-world solutions.

Helmsley Charitable Trust’s T1D Exercise Initiative (T1-DEXI and T1-DEXIP)

In people with type 1 diabetes (T1D), glycemic response to exercise is highly variable, both within and among individuals, often increasing the risk for hypoglycemia and hyperglycemia. The reason(s) behind this variability is largely unknown. While continuous glucose monitors (CGMs) and automated insulin delivery (AID) systems hold promise for improved glycemic control during and after exercise, limited research has been conducted outside of a controlled clinical setting.

To address this gap, Helmsley collaborated with the Jaeb Center for Health Research (JCHR) and a group of investigators to conduct two large observational exercise studies, one for adults (T1-DEXI) and one for pediatrics (T1-DEXIP). While initial investigator-led analyses have been conducted on a subset of study-assigned exercise events (ADA abstracts #1, #2), the majority of the data is yet to be analyzed.

T1-DEXI and T1-DEXIP Data Sets

One of the major outputs of this effort is publicly available data sets, which can be accessible via Vivli, a platform for sharing clinical data. This data is a unique resource to further research, to develop innovative solutions, to improve decision support tools, and to improve automated insulin delivery algorithms. The genotype data, which will be included in the coming weeks, may also provide an opportunity for the data from these studies to be combined with other publicly available data sets and further expand potential use in line with Helmsley’s T1D program’s data sharing goals.

T1-DEXI: The adult study collected 4 weeks of real-life data from approximately 500 people with T1D between the ages of 18 to 70 with T1D wearing a Continuous Glucose Monitor (CGM), using automated insulin delivery (AID) systems, insulin pumps, and multiple daily injections (MDI). During the 4-week real-world observational exercise study period participants were asked to complete at least 150 total minutes of activity per week and use the data collection tools. In addition to typical activity and exercise, each participant was assigned to complete a structured study exercise types: aerobic, high-intensity interval training, or resistance.

T1-DEXIP: The pediatric study was designed to collect 10 days of real-world data from 250 youth with T1D between the ages of 12 to 17 using CGM’s, AID systems, insulin pumps or MDI. 50 of the participants are new onset.

Both study designs include (but are not limited to) the collection and aggregation of the following data around structured and unstructured exercise:

• Physical activity and heart rate data (collected by a wearable device called the Study Watch* by Verily Life Sciences and Polar Chest Band for Adults; collected by Garmin Vivosmart 4 for Pediatrics)
• Insulin use data (collected by pumps or a T1-DEXI APP for Adults and Bant APP for Pediatrics)
• Continuous Glucose Monitoring data (blinded or non-blinded Dexcom G6 Pro/G6)
• Record of participant activity, including activity type, duration, intensity, and classification of setting (competition vs. non-competition), (Data collected by T1-Dexi APP for Adults or collected by Bant App for Pediatrics)
• Record of food intake including time of intake, carbohydrate, and meal size estimation (collected by T1-Dexi APP for Adults and collected by Bant app for Pediatrics) and macronutrient data derived from food photos by Pennington Biomedical Research Center
• Genotype data (Oragene saliva collection kits), in cooperation with the University of Virginia Center for Public Health Genomics

NOTES:

*The Vivli Platform will only have processed activity data. If algorithm research groups are interested in accessing raw activity data (protobin), please contact ddalton@Helmsleytrust.org separately.

Pertinent study resource documents and a metadata file describing dataset contents are available in the Vivli platform. See CDISC section below for additional information.

The links for the study protocols are here: T1-DEXI and T1-DEXIP.

Clinical Data Interchange Standards Consortium (CDISC)

Helmsley partnered with the Clinical Data Interchange Standards Consortium (CDISC) and T1D experts to expand upon existing diabetes standards and to develop new data standards for Type 1 Diabetes exercise, nutrition, pediatrics, and devices.  As part of the Helmsley T1D Program’s data sharing goals, these data standards were used for subsequent T1-DEXI and T1-DEXIP Study Data Tabulation Model (SDTM) tabulations as provided.  Collaboration and subsequent efforts are meant to encourage the use of controlled terminology, promote interoperability and data re-use, and increase operational efficiencies in combining data sets.  We encourage applicant teams to include a statistician, bioinformatician, engineer, data manager, or a colleague with other similar expertise.

Serving as the data dictionary, a Define-XML metadata file describing the contents of each SDTM data set is provided at the Vivli platform.  Additional study documents available to support use of the SDTM data sets include: study protocol, annotated CRFs, and a Study Data Reviewer’s Guide.

VIVLI

Helmsley partnered with Vivli to make the T1-DEXI and T1-DEXIP data sets publicly available and easily accessible. Vivli is an independent, non-profit entity whose mission is to promote, coordinate, and facilitate clinical research data sharing through a global clinical research data sharing platform. The Vivli team is dedicated to helping researchers share and access data from clinical trials to advance science. Furthermore, the Vivli platform hosts other T1D data sets that can be combined with T1-DEXI data. Vivli is also one of six generalist repositories that will work with the National Institute of Health (NIH) Office of Data Science Strategy (ODSS) as part of the Generalist Repository Ecosystem Initiative (GREI).

Helmsley T1D Program seeks to fund studies that lead to solutions that improve management of exercise with T1D in the real world. The goal of the projects should be learning from the T1-DEXI data to provide people with T1D and healthcare providers practical management solutions for T1D and exercise and to improve clinical guidelines in a way that can be applied in the real world. All potential projects are expected to include a study component involving people with T1D.

The following are examples of project ideas that could be applicable for this RFP, however applicants are also encouraged to propose new research directions that may not have been exemplified here:

• Develop or confirm a hypothesis using the T1-DEXI data, and/or combine other relevant data sets to develop effective, feasible and novel solutions, and improve clinical guidelines as well as evaluate the solution/new guidelines with people with T1D (If it is identified that the research project requires additional data collection to build a novel solution, the additional data collection would need to be complimentary to the T1-DEXI data sets)
• Evaluate AID systems with novel exercise algorithms developed based on the insights gained in the T1-DEXI data sets
• Evaluate novel decision support solutions that can improve and simplify management of exercise with T1D (ideally embedded into existing platforms that people with T1D and providers already use)
• Develop novel diabetes device technology interventions and solutions to mitigate hypoglycemia and hyperglycemia in T1D management around exercise including the evaluation of nutrition intake in response to diabetes device data.

NOTE: Excluded from the scope of the funding opportunity are (a) resources to initially look at the data sets and develop the Concept Note for the RFP (b) studies primarily focused on animal model-based activities.

• September 2022: T1-DEXI Adult Data Set Publicly Available
• September/October 2022: Applicants invited to submit Concept Notes
• January 2023: T1-DEXI Pediatric Data Set Publicly Available
• April 30, 2023: Concept Notes due
• May 30, 2023: Selected applicants invited to submit Full Grant Proposals
• June 30, 2023: Full Grant Proposals due
• Fall 2023: Notification of awards

NOTE: Timing of the RFP process is subject to change.

Phase 1: September 2022 – April 30, 2023 (7 months)

Accessing and Exploring the T1-DEXI data sets via Vivli Platform, Registering the Organization with Helmsley Grants Management System & Submitting a Concept Note by April 30, 2022

Phase 1A – Register with Vivli

• Applicants (Principal Investigators) will need to register with Vivli to access and explore the T1-DEXI Adult and T1-DEXIP Pediatric (Available Jan 2023) Data Sets
• At time of registration with Vivli, applicants will be asked to verify whether a data analyses expert [statistician, bioinformatician, other similar titles] will be part of the team analyzing the datasets
• Applicants are invited to use the datasets to generate new hypotheses (or confirm their novel hypothesis), propose new research directions, and/or build new solutions that will help better understand, improve and/or simplify exercise management with T1D for people with T1D.

NOTE: Applicants MUST use the T1-DEXI and/or T1-DEXIP data sets as part of their basis for the proposal. This is a pre-requisite for submitting a Concept Note (due April 30, 2023).

Phase 1B – Register with Fluxx and Submit a Concept Note

• Applicants who accessed the T1-DEXI data in Vivli will receive an email from Helmsley to register with Helmsley’s grants management system (Fluxx) by filling out contact information, organization information, and the title of the proposed project. (Note: Helmsley will send this email to applicants once Vivli confirms access to the T1-DEXI data. Applicants should not reach out to Helmsley for registration information.)
• Following verification of organization information, Helmsley will provide the applicant access to Helmsley’s application portal in Fluxx to submit a Concept Note.
• Concept Notes must be submitted before 11:59 pm EST on April 30, 2023. See Instructions for Concept Note section below.

Phase 2: May 2023 – June 30, 2023 (2-3 months)

After review of Concept Notes, selected applicants will be invited to submit Full Grant Proposals, which will include, but not be limited to:

• Full description of the research project, rationale, and proposed activities;
• Description of project milestones, deliverables, outcomes;
• Project budget; and
• Biosketches of applicants and collaborators.

Helmsley staff will review submitted material. Helmsley may choose to engage external advisors in the review process.

Additionally, if there are algorithm research groups interested in raw data files from the Study Watch, please contact Helmsley (ddalton@helmsleytrust.org) in addition to completing steps above.

Instructions for Concept Note

Applicants should complete the requested information in Fluxx AND upload a Word document or PDF (with figures) of no more than 1,200 words (figures do not count against the word limit) addressing the topics below.

• Background: Provide a summary of preliminary analysis that was done with the T1-DEXI data, identify existing evidence and data that justify the proposed study.
• Activities: Define a specific hypothesis(es) that will be tested. Describe proposed project activities, including the proposed study size, and whether it is clinical or observational. Define risks and outline mitigation strategies.
• Expected outcomes and next steps: Describe what the research plan aims to produce by the end of the funded project.
• Innovation and impact on the field: Describe how your proposed project might advance the field’s understanding of exercise management with T1D and help people with T1D manage exercise.
• Project team and environment: Describe the key members of the project team and the research environment that will impact success of the project.
• High-level budget: Briefly describe the funding needs for each year. 10 percent can be requested to support institutional indirect costs. Detailed budgets are not needed at this time

Funding

The proposed funding term can be up to three years. If additional years are required, describe the project in stages, with the first stage lasting up to three years. Requested funding amounts can range, based on activities, but should not exceed $3M over three years. If the research plan cannot be executed within the funding opportunity’s boundaries, justify an alternative in the Concept Note. All funding decisions are subject to approval by Helmsley’s Board of Trustees.

Review Criteria

Proposed projects will be assessed based on:

• Impact on improving management of exercise with T1D, health and quality of life outcomes;
• Feasibility, Scalability and novelty of the proposed activities;
• Expected outcomes of the scientific plan;
• Likelihood for discoveries or progress; and
• The project team and research environment.

Eligibility

Any individual with a faculty-level (or equivalent) appointment at an institution performing medical research, with the skills, knowledge, and resources (individual and institutional) necessary to carry out the proposed research is invited to work with their organization to develop an application for support. Non-US institutions invited to submit a Full Grant Proposal will be required to submit additional information at that stage.

Questions?

Direct any application-related questions to:

Deniz Dalton, T1D Program Officer (ddalton@helmsleytrust.org)

Sean Sullivan, T1D Program Officer (ssullivan@helmsleytrust.org)

Grants Management (fluxxhelp@helmlseytrust.org) for technical assistance.

Applicants (Principal Investigators) will need to register with Vivli to access and explore the T1-DEXI Adult and T1-DEXIP Pediatric Data Sets

Access T1Dexi Adult Data Set on Vivli

Access Pediatric Data Set on Vivli