Diabetes RElated to Acute Pancreatitis and Its Mechanisms: Metabolic Outcomes Using Novel CGM Metrics

Official title

Diabetes RElated to Acute Pancreatitis and Its Mechanisms: Metabolic Outcomes Using Novel CGM Metrics (DREAM-ON) - An Observational Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)

Overview

The DREAM-ON study will investigate whether continuous glucose monitoring (CGM) is useful to predict risk for developing diabetes mellitus (DM) and pre-diabetes mellitus (PDM), the need for insulin therapy among those who develop DM, and to determine whether CGM can provide insight into the pathophysiology and DM subtype among participants who have experienced an episode of acute pancreatitis (AP). Thus, the results of the DREAM-ON study could inform future clinical practice guidelines for the management AP as well as potentially extending the licensing authorization for CGM to include use in patients with pancreatogenic (Type 3c) DM.

Detailed description

The primary objective of the DREAM-ON study is to determine if continuous glucose monitoring (CGM) metrics can predict the incidence of prediabetes mellitus (PDM) and diabetes mellitus (DM) after an episode of acute pancreatitis (AP). Secondary objectives of the DREAM-ON study include determining if CGM metrics predict the need for insulin therapy in participants who develop diabetes mellitus after AP, and if CGM metrics correlate with measures of insulin secretion and insulin resistance.

The specific aims of the DREAM-ON study are as follows:

Aim 1: To test whether standard CGM metrics predict incident DM. The investigators will perform blinded CGM in DREAM-ON participants at their scheduled visits at months 3, 12, 24 and subsequent annual visits. The investigators will test whether standard CGM metrics (mean glucose, time in tight range 70-140, time in range 70-180, time above 180 mg/dL, time above 250 mg/dL and glucose CV) predict incident DM determined by fasting plasma glucose (FPG), HbA1c, oral glucose tolerance testing (OGTT) and clinical report.

Aim 2: To test whether CGM metrics predict need for insulin therapy in patients who develop DM after AP. From blinded CGM, we will test whether standard CGM metrics (mean glucose, time in tight range 70-140, time in range 70-180, time above 180 mg/dL, time above 250 mg/dL and glucose CV) as well as other indices of glucose variability, including mean amplitude of glycemic excursions (MAGE), predict need for long-term insulin therapy.

Aim 3: To determine whether CGM metrics correlate with measures of insulin secretion and insulin resistance. The investigators will test whether standard and advanced CGM metrics correlate with measures of insulin secretion and insulin resistance derived from the OGTT, the mixed meal tolerance test (MMT) and the frequently sampled intravenous glucose tolerance test (FSIGTT). The investigators also will test whether these metrics can be used as a surrogate to predict diabetes subtype (i.e., insulin deficient vs. insulin resistant).

Interventions

• Device Dexcom Continuous Glucose Monitor (CGM)
  Dexcom Continuous Glucose Monitor which measures and records a participant's serum glucose level

Primary outcome measures

• pre-diabetes mellitus following an episode of acute pancreatitis [Time frame: any time during the 36-month longitudinal follow-up period]
• diabetes mellitus following an episode of acute pancreatitis [Time frame: any time during the 36-month longitudinal follow-up period]

Secondary outcome measures (7)

• initiation of insulin therapy [Time frame: any time during the 36-month longitudinal follow-up period]
• insulin secretion [Time frame: during the oral glucose tolerance test (OGTT) administered at 3, 12, 24, and 36 months]
• insulin sensitivity [Time frame: during the oral glucose tolerance test (OGTT) administered at 3, 12, 24, and 36 months]
• fasting glucose [Time frame: during the mixed meal tolerance test (MMTT) administered at 3, 12, 24, and 36 months]
• peak value glucose [Time frame: during the mixed meal tolerance test (MMTT) administered at 3, 12, 24, and 36 months]
• meal-stimulated insulin [Time frame: during the mixed meal tolerance test (MMTT) administered at 3, 12, 24, and 36 months]
• acute insulin response to glucose [Time frame: during the frequently sampled intravenous glucose tolerance test (FSIGTT) administered at 3 and 12 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Diagnosis of definite chronic pancreatitis (CP) at enrollment (see also study definitions) 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 (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 diabetes mellitus 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 estimated glomerular filtration rate (eGFR) < 30 or on dialysis prior to AP, and decompensated 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 as detailed in the Manual of Procedures
• Incarceration
• Any other condition or factor that would compromise the participant's safety or the scientific integrity of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 13 centers

• University of Southern California — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles
• Stanford University — Stanford
• University of Florida — Gainesville
• AdventHealth — Orlando
• Northwestern University — Chicago
• University of Illinois at Chicago — Chicago
• Indiana University — Indianapolis
• … and 5 more centers

Identifiers

NCT: NCT06401577 · STUDY00015937 · R01DK138060 · U01DK127384

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗