RFA-DK-19-022: Type 1 Diabetes in Acute Pancreatitis Consortium – Clinical Centers (T1DAPC-CCs) (U01 Clinical Trial Optional)
Internal Deadline: Contact Office of Research if interested.
LOI: February 13, 2020
External Deadline: March 13, 2020
Award Information: Type: Cooperative Agreement
Estimated Number of Awards: 10
Anticipated Amount: $2.7 million
Submission Process: PIs must submit their application as a Limited Submission through the Office of Research Application Portal: https://app.wizehive.com/webform/USCgrants
Materials to submit:
- Single Page Proposal Summary (0.5” margins; single-spaced; font type: Arial, Helvetica, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 1-page limit will be excluded from review.
- CV – (5 pages maximum)
Who May Serve as PI: Standard NIH eligibility requirements.
The overriding objective of this research program is to undertake a prospective longitudinal observational clinical study to investigate the incidence, etiology and pathophysiology of diabetes following acute pancreatitis with a particular emphasis on the auto-immune processes that result in T1D. The incidence, timecourse, and relationship to pancreatitis severity, the roles of pancreatitis etiology, genetic and genomic risk factors, environmental and biological factors and potential biomarkers for the development of T1D are subjects of interest.
Through the acquisition of a cohort of well characterized patients monitored over time for diabetes onset and T1D-associated autoantibodies, and collected biospecimens (blood, saliva, urine, pancreatic and duodenal juice, stools and when feasible pancreatic tissue), the proposed clinical research consortium will provide the resources and collaborative opportunities necessary to identify the interrelationship between the exocrine and the endocrine pancreas in the development of post-pancreatitis diabetes.
The primary study design will be a longitudinal study of adults (age 18 years and older) who have experienced one or more episodes of acute pancreatitis in whom periodic glucose tolerance testing identifies subjects who develop impaired glucose tolerance (IGT) or diabetes after the onset of the acute pancreatitis over a period of at least three years. The type of diabetes which occurs after acute pancreatitis will be characterized using biomarkers of T1D (e.g., anti-islet and anti-insulin antibodies), T2D (e.g., measures of insulin sensitivity) and Type 3c diabetes (T3cD) (e.g., basal and post-test meal levels of pancreatic polypeptide and other biomarkers of T3cD) to determine the prevalence of T1D among all subjects with diabetes which occurs after or as a consequence of acute pancreatitis. Applicant teams should have expertise in Pancreatology, Endocrinology and Diabetology. Applicants must provide information regarding a) their capability to identify patients with Acute Pancreatitis (AP) and Recurrent Acute Pancreatitis (RAP) and their approach to ascertain the development of impaired glucose tolerance and diabetes and of the development of T1D in particular; b) their enrollment capacity to contribute to the collaborative efforts of the T1DAPC and c) proposed protocols and ancillary studies for post-award consideration by the Consortium Steering Committee.
Examples of possible additional objectives and ancillary projects include but are not limited to:
- Studies that identify patients at “higher risk” for the development of post-acute pancreatitis T1D (post AP-T1D) through development of biomarkers, algorithms, and the clinical features such as the etiology or the course of acute pancreatitis
- Studies addressing the mechanisms by which AP causes Type 1 Diabetes (T1D) including the longitudinal assessment of auto-immune biomarkers and the timecourse of the appearance of evidence of auto-immunity with the subsequent development of T1D
- Studies addressing the mechanisms by which post AP-T1D affects the prognosis of acute pancreatitis and the likelihood of recurrence
- Studies that examine the role of genetic risk factors in post AP-T1D and their implication for prognosis and treatment response
- Evaluation of non-invasive methods to detect, quantify, and measure the impact of post AP T1D on exocrine function
- Studies of the microbiome and genome in patients with acute pancreatitis experiencing post AP -T1D
- Characterization of the timecourse of the progression of IGT to the types of diabetes which occur after acute pancreatitis, including associations with age, gender, race, ethnicity, family history, and personal history of illness, medications, and travel
- Studies of HLA haplotypes and genetic loci that are associated with T1D and their appearance in acute pancreatitis before and after the emergence of T1D
- Studies of cytokines and inflammatory elements that are altered in acute pancreatitis and which are likely to play a role in the induction of the auto-immune response to injury in patients with acute pancreatitis
- Studies to determine whether the degree or location of pancreatic necrosis (determined by standardized imaging methods) correlates with the development and severity of diabetes in general and in the development of T1D in particular in survivors of acute pancreatitis
- Studies which correlate the morphology of the pancreas at the onset of acute pancreatitis or during its course with the development of post AP-T1D
Budgetary Requirements: Application budgets are not limited but need to reflect the actual needs of the proposed project. No more than $175,000 in direct costs per year may be requested for support of PDs/PIs and travel.
Visit our Institutionally Limited Submission webpage for updates and other announcements.