Diabetes RElated to Acute Pancreatitis and Its Mechanisms (DREAM)

• ClinicalTrials.gov Identifier: NCT05197920
• Recruitment Status: Recruiting
• First Posted: January 20, 2022
• Last Update Posted: May 6, 2024
• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Benaroya Research Institute; Cedars-Sinai Medical Center; University of Southern California; Indiana University; Johns Hopkins University; Ohio State University; Stanford University; University of Florida; AdventHealth; University of Illinois at Chicago; Northwestern University; University of Minnesota; University of Pittsburgh
• Information provided by (Responsible Party): Vernon Michael Chinchilli, Milton S. Hershey Medical Center

Tracking Information

• First Submitted Date: December 11, 2021
• First Posted Date: January 20, 2022
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: January 14, 2022
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

diabetes mellitus (DM) following a qualifying episode of acute pancreatitis (AP) [ Time Frame: any time during the 36-month longitudinal follow-up period ]

time to onset of DM during the 36-month longitudinal follow-up period

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 14, 2022)

• PROMIS Global Health [ Time Frame: 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
• PROMIS Pain Intensity [ Time Frame: 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 [ Time Frame: 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
• PROMIS-29 Anxiety [ Time Frame: 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 Depression [ Time Frame: 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 Fatigue [ Time Frame: 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 Sleep Disturbance [ Time Frame: 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 Ability to Participate in Social Roles and Activities [ Time Frame: 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
• PROMIS-29 Pain Interference [ Time Frame: 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
• OGTT Insulin Secretion [ Time Frame: 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
• OGTT Insulin Sensitivity Index [ Time Frame: 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
• MMTT Incretin Hormones: GIP and GLP-1 [ Time Frame: 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)
• MMTT Glucagon [ Time Frame: months 3, 12, 24, and 36 ]
  Mixed Meal Tolerance Testing (MMTT) Glucagon (pg/mL)
• MMTT Pancreatic Polypeptide (PP) [ Time Frame: months 3, 12, 24, and 36 ]
  Mixed Meal Tolerance Testing (MMTT) Pancreatic Polypeptide (PP, pg/mL)
• FSIGTT Acute Insulin Response to Glucose (AIRglu) [ Time Frame: 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) [ Time Frame: months 3 and 12 ]
  Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Acute C-peptide Response to Glucose (ACRglu)
• FSIGTT Total Body Insulin Sensitivity Index (SI) [ Time Frame: months 3 and 12 ]
  Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Total Body Insulin Sensitivity Index (SI)
• FSIGTT Total Body Insulin Sensitivity Index (SI) Disposition Index [ Time Frame: 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
• Islet Autoantibodies [ Time Frame: months 3, 12, 24, and 36 ]
  Islet Autoantibodies
• Fecal Elastase [ Time Frame: months 3, 12, 24, and 36 ]
  Fecal Elastase (ug/g)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

blood (fasting blood glucose, islet autoantibodies, creatinine, complete blood count (CBC), RNAseq), stool (fecal elastase)

• Sampling Method: Non-Probability Sample
• Study Population: Patients hospitalized for acute pancreatitis
• Condition: Acute Pancreatitis
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 14, 2022): 800
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2025
• Estimated Primary Completion Date: April 30, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Melissa A Butt, DrPH; 717-531-1258; mbutt1@pennstatehealth.psu.edu

Contact: Kendall T Baab, BS; 717-531-6308; kthomas4@pennstatehealth.psu.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05197920
• Other Study ID Numbers: Penn State College of Medicine; U01DK127384 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data from final locked datasets will be made available to other researchers outside the DREAM investigative team. The plan for data sharing incorporates a strategy that recognizes the importance of protecting participants' rights to individual privacy and is compliant with HIPAA regulations and NIH requirements (https://grants.nih.gov/grants/policy/data_sharing/).
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: The data will become available one year after publication of the primary manuscript of the DREAM study. The data will be available indefinitely at the NIDDK Central Repository.

Access Criteria

Instructions for requesting data from the NIDDK Central Repository appear at the following web site:

https://repository.niddk.nih.gov/pages/overall_instructions/

• URL: https://repository.niddk.nih.gov/home/

• Current Responsible Party: Vernon Michael Chinchilli, Milton S. Hershey Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Milton S. Hershey Medical Center
• Original Study Sponsor: Same as current

Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Benaroya Research Institute
• Cedars-Sinai Medical Center
• University of Southern California
• Indiana University
• Johns Hopkins University
• Ohio State University
• Stanford University
• University of Florida
• AdventHealth
• University of Illinois at Chicago
• Northwestern University
• University of Minnesota
• University of Pittsburgh

Investigators

• Principal Investigator: Vernon M Chinchilli, PhD; Penn State College of Medicine
• Study Chair: Dhiraj Yadav, MD, MPH; University of Pittsburgh
• Study Chair: Melena D Bellin, MD; University of Minnesota
• Study Chair: Phillip A Hart, MD; Ohio State University

• PRS Account: Milton S. Hershey Medical Center
• Verification Date: May 2024