Clinical trial NCT05197920: Diabetes RElated to Acute Pancreatitis and Its Mechanisms
Official title: Diabetes RElated to Acute Pancreatitis and Its Mechanisms (DREAM) An Observational Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Pancreatitis
Keywords: Diabetes
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Benaroya Research Institute
name: Cedars-Sinai Medical Center
name: University of Southern California
name: Indiana University
name: Johns Hopkins University
name: Ohio State University
name: Stanford University
name: University of Florida
name: AdventHealth
name: University of Illinois at Chicago
name: Northwestern University
name: University of Minnesota
name: University of Pittsburgh
First posted: 2022-01-20
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients hospitalized for acute pancreatitis

Brief summary: The overriding objective of DREAM is to conduct a prospective longitudinal (36 months) observational clinical study to investigate the incidence, etiology, and pathophysiology of diabetes mellitus (DM) following acute pancreatitis (AP).

Detailed description: The DREAM investigators will conduct dynamic metabolic testing that includes oral glucose tolerance testing (OGTT), mixed meal tolerance testing (MMTT), and frequently sampled intravenous glucose tolerance testing (FSIGTT). These tests will increase the sensitivity for DM diagnosis (with OGTT) and to assess beta cell function and other pancreatic and enteroendocrine hormones involved in maintaining glucose homeostasis (OGTT, MMTT and FSIGTT). The DREAM research hypotheses are as follows.

1. There is a cumulative increase in the risk of any type of DM after an episode of AP, and the development of DM after AP is influenced by several patient and disease-related factors (e.g. age, etiology, disease severity).
2. After AP is clinically resolved, there is ongoing subclinical beta cell damage that predisposes to delayed-onset of DM.
3. AP triggers an altered immune state in a subset of individuals that predisposes to islet autoimmunity and DM.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of acute pancreatitis (AP) 0-90 days prior to enrollment date
* Participant fully understands and is able to participate in all aspects of the study, including providing informed consent, completion of case report forms (CRFs), telephone interviews, metabolic testing, and planned longitudinal follow-ups

Exclusion Criteria:

* Diagnosis of definite chronic pancreatitis (CP) at enrollment based on either of the following criteria met by computed tomography (CT) scan (including non-contrast enhanced) or Magnetic resonance Imaging (MRI) or Magnetic Resonance Cholangiopancreatography (MRCP): (a) Parenchymal or ductal calcifications on CT scan (after excluding the possibility that calcifications are vascular); (b) Intraductal filling defects suggestive of calcifications on MRI and/or MRCP
* Potential participants with post-endoscopic retrograde cholangiopancreatography (post- ERCP) AP who are hospitalized for \<48 hours.
* Prior (i.e., before enrollment) direct endoscopic necrosectomy of the pancreas or percutaneous necrosectomy or drainage of necrotic collection(s). Participants who require this during follow-up will remain in the study
* Pancreatic tumors, including ductal adenocarcinoma, neuroendocrine tumors, and metastasis
* Confirmed or suspected cystic tumor associated with main pancreatic duct dilation, or believed to be the cause of AP (in the site-PI's judgement)
* Prior pancreatic surgery, including, but not limited to: distal pancreatectomy, pancreaticoduodenectomy, pancreatic necrosectomy, Frey procedure
* Use of disallowed concomitant medications within 30 days prior to enrollment. A comprehensive list of disallowed medications will be included and routinely updated in the study's Manual of Procedures
* Severe systemic illness that in the judgement of the investigative team will confound outcome assessments of DM and immunological outcomes or pose additional risk for harms, including: history of solid organ transplant, acquired immunodeficiency syndrome (AIDS), active treatment for cancer (except non-melanoma skin cancer) within 12 months prior to enrollment, chronic kidney disease with estimate glomerular filtration rate (eGFR) \< 30 or on dialysis prior to AP, and cirrhosis (based on imaging or biopsy), or any other medical condition that in the opinion of the site-PI carries a life expectancy of \<12 months.
* Known pregnancy at the time of enrollment. Participants who become pregnant during follow-up will remain in the study, but may have modified study assessments for safety
* Incarceration
* Any other condition or factor that would compromise the participant's safety or the scientific integrity of the study

Primary outcomes:
measure: diabetes mellitus (DM) following a qualifying episode of acute pancreatitis (AP)
timeFrame: any time during the 36-month longitudinal follow-up period
Secondary outcomes:
measure: PROMIS Global Health
timeFrame: months 3, 12, 24, and 36
measure: PROMIS Pain Intensity
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Physical Function
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Anxiety
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Depression
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Fatigue
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Sleep Disturbance
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Ability to Participate in Social Roles and Activities
timeFrame: months 3, 12, 24, and 36
measure: PROMIS-29 Pain Interference
timeFrame: months 3, 12, 24, and 36
measure: OGTT Insulin Secretion
timeFrame: months 3, 12, 24, and 36
measure: OGTT Insulin Sensitivity Index
timeFrame: months 3, 12, 24, and 36
measure: MMTT Incretin Hormones: GIP and GLP-1
timeFrame: months 3, 12, 24, and 36
measure: MMTT Glucagon
timeFrame: months 3, 12, 24, and 36
measure: MMTT Pancreatic Polypeptide (PP)
timeFrame: months 3, 12, 24, and 36
measure: FSIGTT Acute Insulin Response to Glucose (AIRglu)
timeFrame: months 3 and 12
measure: FSIGTT Acute C-peptide Response to Glucose (ACRglu)
timeFrame: months 3 and 12
measure: FSIGTT Total Body Insulin Sensitivity Index (SI)
timeFrame: months 3 and 12
measure: FSIGTT Total Body Insulin Sensitivity Index (SI) Disposition Index
timeFrame: months 3 and 12
measure: Islet Autoantibodies
timeFrame: months 3, 12, 24, and 36
measure: Fecal Elastase
timeFrame: months 3, 12, 24, and 36
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: AdventHealth
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Seattle
country: United States
facility: Benaroya Research Institute
state: Washington
Study officials:
affiliation: Penn State College of Medicine
name: Vernon M Chinchilli, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Dhiraj Yadav, MD, MPH
role: STUDY_CHAIR
affiliation: University of Minnesota
name: Melena D Bellin, MD
role: STUDY_CHAIR
affiliation: Ohio State University
name: Phillip A Hart, MD
role: STUDY_CHAIR
References: