Diabetes RElated to Acute Pancreatitis and Its Mechanisms
- Conditions
- Acute Pancreatitis
- Registration Number
- NCT05197920
- Lead Sponsor
- Milton S. Hershey Medical Center
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 800
- 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
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method diabetes mellitus (DM) following a qualifying episode of acute pancreatitis (AP) any time during the 36-month longitudinal follow-up period time to onset of DM during the 36-month longitudinal follow-up period
- Secondary Outcome Measures
Name Time Method PROMIS-29 Anxiety months 3, 12, 24, and 36 PROMIS-29 Anxiety, converted to a t-score with a mean of 50 and a standard deviation of 10
PROMIS-29 Fatigue months 3, 12, 24, and 36 PROMIS-29 Fatigue, converted to a t-score with a mean of 50 and a standard deviation of 10
PROMIS-29 Ability to Participate in Social Roles and Activities months 3, 12, 24, and 36 PROMIS-29 Ability to Participate in Social Roles and Activities, converted to a t-score with a mean of 50 and a standard deviation of 10
FSIGTT Total Body Insulin Sensitivity Index (SI) months 3 and 12 Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Total Body Insulin Sensitivity Index (SI)
Islet Autoantibodies months 3, 12, 24, and 36 Islet Autoantibodies
MMTT Pancreatic Polypeptide (PP) months 3, 12, 24, and 36 Mixed Meal Tolerance Testing (MMTT) Pancreatic Polypeptide (PP, pg/mL)
PROMIS Pain Intensity months 3, 12, 24, and 36 Patient Reported Outcomes Measurement Information System (PROMIS) Pain Intensity, measured on an 11-point scale from 0 (no pain ) to 10 (worst pain imaginable)
PROMIS-29 Physical Function months 3, 12, 24, and 36 PROMIS-29 Physical Function, converted to a t-score with a mean of 50 and a standard deviation of 10
OGTT Insulin Sensitivity Index months 3, 12, 24, and 36 Oral Glucose Tolerance Testing (OGTT) Insulin Sensitivity Index, as measured by the glucose disposal rate divided by the average plasma insulin concentration
FSIGTT Total Body Insulin Sensitivity Index (SI) Disposition Index months 3 and 12 Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Disposition Index (DI), calculated as the product of the AIRglu and the Total Body Insulin SI
Fecal Elastase months 3, 12, 24, and 36 Fecal Elastase (ug/g)
PROMIS Global Health months 3, 12, 24, and 36 Patient Reported Outcomes Measurement Information System (PROMIS) Global Health, converted to a t-score with a mean of 50 and a standard deviation of 10
OGTT Insulin Secretion months 3, 12, 24, and 36 Oral Glucose Tolerance Testing (OGTT) Insulin Secretion, as measured by the insulin area under the curve relative to the glucose area under the curve
MMTT Glucagon months 3, 12, 24, and 36 Mixed Meal Tolerance Testing (MMTT) Glucagon (pg/mL)
PROMIS-29 Depression months 3, 12, 24, and 36 PROMIS-29 Depression, converted to a t-score with a mean of 50 and a standard deviation of 10
PROMIS-29 Sleep Disturbance months 3, 12, 24, and 36 PROMIS-29 Sleep Disturbance, converted to a t-score with a mean of 50 and a standard deviation of 10
PROMIS-29 Pain Interference months 3, 12, 24, and 36 PROMIS-29 Pain Interference, converted to a t-score with a mean of 50 and a standard deviation of 10
MMTT Incretin Hormones: GIP and GLP-1 months 3, 12, 24, and 36 Mixed Meal Tolerance Testing (MMTT) Incretin Hormones: Glucose-dependent Insulinotropic Polypeptide (GIP, pmol/L) and Glucagon-like Peptide-1 (GLP-1, pmol/L)
FSIGTT Acute Insulin Response to Glucose (AIRglu) months 3 and 12 Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Acute Insulin Response to Glucose (AIRglu)
FSIGTT Acute C-peptide Response to Glucose (ACRglu) months 3 and 12 Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Acute C-peptide Response to Glucose (ACRglu)
Trial Locations
- Locations (13)
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Benaroya Research Institute
🇺🇸Seattle, Washington, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Stanford, California, United States
AdventHealth
🇺🇸Orlando, Florida, United States