Clinical trial NCT06729996: Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis Associated Diabetes Mellitus
Official title: Randomized, Parallel Group, Dose Escalation Trial of Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis Associated Diabetes Mellitus: The PEP-DM Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pancreatitis, Chronic
Pancreatitis, Acute
Diabetes Mellitus
Keywords: pancreatitis
diabetes
diabetes mellitus
empagliflozin
pioglitazone
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh Medical Center
First posted: 2024-12-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy of pioglitazone (PIO) versus empagliflozin (EMPA) to improve glycemic control in people with Chronic Pancreatitis (CP) or Recurrent Acute Pancreatitis (RAP) associated with Diabetes Mellitus (DM). To evaluate mixed meal response in PIO versus EMPA group to better understand physiology of both therapies in CP-DM.

Detailed description: This trial will test the efficacy of PIO versus EMPA in improving glycemic control in CP-DM. The anticipated enrollment will consist of 40 subjects, age 18-70 years who have been diagnosed with CP or RAP with DM, at two clinical sites in the United States. The primary objective is to evaluate the efficacy of PIO vs. EMPA to improve glycemic control in people with CP or RAP associated with DM.

Eligibility criteria: Inclusion Criteria:

* Age ≥18-70 years at the time of enrollment.
* RAP or CP with DM diagnosed before or after CP diagnosis (Confirmed CP on imaging or RAP based on PROCEED study criteria, and confirmed DM as per ADA criteria or clinically diagnosed with DM and on antihyperglycemic therapy)
* Able to provide written informed consent and participate in longitudinal follow-up
* Stable last annual retinal exam within 1 year prior to enrollment.
* HbA1c level 7-10% at screening visit.
* Fasting plasma glucose \<220 mg/dL at screening visit.
* Not on any antihyperglycemic medication except Metformin
* Willing to perform blood glucose and ketone testing on study provided meters as per study protocol.

Exclusion Criteria:

* Inability to take PIO or EMPA due to prior hypersensitivity or allergic reaction or current use of medications with potential for drug-drug interactions (Pioglitazone: Drug information - UpToDate, Empagliflozin: Drug information - UpToDate)
* Diagnosed with Type 1 Diabetes
* Pregnancy or lactation in women (positive urine pregnancy test at screening will lead to exclusion)
* History of bleeding disorders (e.g., Hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), von Willebrand disease, platelet disorders etc)
* Presence of hepatic impairment, ALT \>3 x ULN with no etiology known at the time of enrollment or any evidence of acute/chronic liver disease
* Ongoing treatment for any malignancy requiring systemic treatment (non-melanoma skin cancers treated in dermatologists' office would be acceptable)
* Presence of osteoporosis (the threshold of bone density value below the -2.5 SDS of T-score or presence of one or more fragility fractures), on electronic medical record.
* Recent inflammatory illness within the 30 days preceding enrollment (e.g.: URTI, episode of AP, etc)
* History of heart failure classified by New York Heart Association as Class III or greater
* History of kidney dysfunction classified by eGFR of \<30 mL/min/min
* Participation in any clinical trial within 30 days before screening for an approved or non-approved investigational medical product.
* Active alcohol dependence or chemical dependence including tobacco based on investigator discretion
* On a ketogenic diet
* Autoimmune pancreatitis, obstructive pancreatitis, and prior surgery of pancreas
* Any condition which could jeopardize participant safety as per investigator opinion, (hemolytic anemia limiting HbA1c reliability, any evidence of fluid overload, presence of Congestive heart failure etc).
* Recent DKA or signs of decompensated diabetes in last 6 months or increased β hydroxybutyrate levels (\>0.4 mmol/L) at screening.

Primary outcomes:
measure: Hemoglobin A1c (HbA1c)
timeFrame: Baseline to 24 weeks
measure: Area under curve (AUC) for glucose
timeFrame: Baseline to 24 weeks
measure: AUC for C-peptide
timeFrame: Baseline to 24 weeks
measure: AUC for Insulin
timeFrame: Baseline to 24 weeks
measure: AUC for glucagon
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Fasting plasma glucose
timeFrame: Baseline to 24 weeks
measure: Lean mass
timeFrame: Baseline to 24 weeks
measure: Fat mass
timeFrame: Baseline to 24 weeks
measure: Visceral fat
timeFrame: Baseline to 24 weeks
measure: Fecal elastase
timeFrame: Baseline to 24 weeks
measure: High Sensitivity C-Reactive Protein (Hs-CRP)
timeFrame: Baseline to 24 weeks
measure: Total cholesterol, LDL, HDL and Triglyceride
timeFrame: Baseline to 24 weeks
measure: β-Hydroxybutyrate
timeFrame: Baseline to 24 weeks
measure: Body weight
timeFrame: Baseline to 24 weeks
measure: Blood Pressure
timeFrame: Baseline to 24 weeks
measure: Body Mass Index (BMI)
timeFrame: Baseline to 24 weeks
measure: Patient-Reported Outcomes Measurement Information System - 29 Profile v2.1 (PROMIS-29 Profile v2.1)
timeFrame: Baseline to 24 weeks
measure: Insulin sensitivity
timeFrame: Baseline to 24 weeks
measure: Beta cell function
timeFrame: Baseline to 24 weeks
Other outcomes:
measure: Ketosis
timeFrame: Baseline to 24 weeks
measure: Diabetic Ketoacidosis (DKA) events
timeFrame: Baseline to 24 weeks
measure: Insulin needs
timeFrame: Baseline to 24 weeks
measure: Chronic pancreatitis exacerbation
timeFrame: Baseline to 24 weeks
measure: Acute pancreatitis episodes
timeFrame: Baseline to 24 weeks
measure: Exocrine pancreatic insufficiency
timeFrame: Baseline to 24 weeks
measure: Vitamin D
timeFrame: Baseline to 24 weeks
measure: Bone fractures
timeFrame: Baseline to 24 weeks
measure: Adverse events
timeFrame: Baseline to 24 weeks
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: Mayo Clinic
name: Yogish Kudva
role: PRINCIPAL_INVESTIGATOR
References: