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 17, 2022
• 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

Study Description

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).

Condition or disease
Acute Pancreatitis

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 Design

• Study Type: Observational
• Estimated Enrollment: 800 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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)
• Actual Study Start Date: January 14, 2022
• Estimated Primary Completion Date: April 30, 2025
• Estimated Study Completion Date: April 30, 2025

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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
2. 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)
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
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
11. 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
12. 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)
13. MMTT Glucagon [ Time Frame: months 3, 12, 24, and 36 ]
    Mixed Meal Tolerance Testing (MMTT) Glucagon (pg/mL)
14. MMTT Pancreatic Polypeptide (PP) [ Time Frame: months 3, 12, 24, and 36 ]
    Mixed Meal Tolerance Testing (MMTT) Pancreatic Polypeptide (PP, pg/mL)
15. 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)
16. 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)
17. 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)
18. 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
19. Islet Autoantibodies [ Time Frame: months 3, 12, 24, and 36 ]
    Islet Autoantibodies
20. Fecal Elastase [ Time Frame: months 3, 12, 24, and 36 ]
    Fecal Elastase (ug/g)

Biospecimen Retention:   Samples Without DNA

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized for acute pancreatitis

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

Contacts and Locations

Contacts

Contact: Anne-Marie Dyer, MS; 717-531-4232; adyer@phs.psu.edu

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

Locations

United States, California

University of Southern California; Recruiting

Los Angeles, California, United States, 90033

Contact: Jessica Serna 323-409-6939 sernaj@usc.edu

Principal Investigator: James L Buxbaum, MD

Cedars-Sinai Medical Center; Recruiting

Los Angeles, California, United States, 90048

Contact: Eleanor Chang 310-423-0747 eleanor.chang@cshs.org

Principal Investigator: Mark O Goodarzi, MD, PhD

Principal Investigator: Stephen J Pandol, MD

Stanford University; Recruiting

Stanford, California, United States, 94305

Contact: Breanna Collins 650-723-4519 collinsb@standord.edu

Principal Investigator: Walter Park, MD

Principal Investigator: Marina Basina, MD

United States, Florida

University of Florida; Recruiting

Gainesville, Florida, United States, 32610-0214

Contact: Amber Bouton 352-273-9774 amber.bouton@surgery.ufl.edu

Principal Investigator: Chris Forsmark, MD

Principal Investigator: Steven J Hughes, MD

AdventHealth; Recruiting

Orlando, Florida, United States, 32804

Contact: Gina Mercouffer 407-303-7106 Gina.Mercouffer@adventHealth.com

Principal Investigator: Richard E Pratley, MD

United States, Illinois

Northwestern University; Recruiting

Chicago, Illinois, United States, 60611

Contact: Christine Nelson 312-695-4513 c-ebert@northwestern.edu

Principal Investigator: Rajesh N Keswani, MD, MS

University of Illinois at Chicago; Recruiting

Chicago, Illinois, United States, 60612

Contact: Haya Al Rashdan 312-413-0306 halras2@uic.edu

Principal Investigator: Cemal Yazici, MD, MSc

Principal Investigator: Brian Layden, MD

United States, Indiana

Indiana University; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Maureen Mullen-Montagano 317-274-7677 maamulle@iu.edu

Principal Investigator: Evan L Fogel, MD

Principal Investigator: Carmella Evans-Molina, MD, PhD

United States, Maryland

Johns Hopkins University; Recruiting

Baltimore, Maryland, United States, 21205

Contact: Mahya Faghih 443-287-4680 mfaghih2@jhu.edu

Principal Investigator: Vikesh Singh, MD, MSc

Principal Investigator: Zhaoli Sun, MD, PhD

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55454

Contact: Heather Hodgkins 612-626-5293 Hodg0007@umn.edu

Principal Investigator: Melena D Bellin, MD

Principal Investigator: Guru Trikudanathan, MD

United States, Ohio

Ohio State University; Recruiting

Columbus, Ohio, United States, 43210

Contact: Zoe Krebs 614-685-6374 Zoe.krebs@osumc.edu

Principal Investigator: Darwin Conwell, MD, MS

Principal Investigator: Phillip A Hart, MD

Principal Investigator: Georgios Papchristou, MD, PhD

United States, Pennsylvania

University of Pittsburgh; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Shari Reynolds 412-383-0570 Reynoldss12@upmc.edu

Principal Investigator: Dhiraj Yadav, MD, MPH

Principal Investigator: Frederico GS Toledo, MD

United States, Washington

Benaroya Research Institute; Recruiting

Seattle, Washington, United States, 98101

Contact: Kim Varner 206-341-8936 kvarner@benaroyaresearch.org

Principal Investigator: Carla J Greenbaum, MD

Principal Investigator: Richard A Kozarek, MD

Sponsors and Collaborators

Milton S. Hershey Medical Center

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

More Information

Additional Information:

Public web site for the Type 1 Diabetes in Acute Pancreatitis Consortium 

• Responsible Party: Vernon Michael Chinchilli, Distinguished Professor, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT05197920
• Other Study ID Numbers: Penn State College of Medicine; U01DK127384 ( U.S. NIH Grant/Contract )
• First Posted: January 20, 2022
• Last Update Posted: May 17, 2022
• Last Verified: May 2022

Individual Participant Data (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; Statistical Analysis Plan (SAP); 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/

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

Keywords provided by Vernon Michael Chinchilli, Milton S. Hershey Medical Center:

Diabetes

Additional relevant MeSH terms:

Pancreatitis; Pancreatic Diseases; Digestive System Diseases