Diabetes Mellitus, Pancreatitis, Acute, Pancreatitis, Chronic
Conditions
Keywords
pancreatitis, diabetes, diabetes mellitus, empagliflozin, pioglitazone
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 18-80 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.
Interventions
Subjects will take 30 mg tablet, once daily in the morning, taken with or without food for 12 weeks and after 12 weeks dose will be escalated to 45 mg based on Hemoglobin A1c (HbA1c) levels (HbA1c \>7.0% at 12 weeks, escalate the dose) once daily in the morning, taken with or without food till 24 weeks.
Subjects will start with 10 mg dose, once daily in the morning, taken with or without food for 12 weeks and after 12 weeks dose will be escalated to 25 mg based on Hemoglobin A1c (HbA1c) levels (HbA1c \>7.0% at 12 weeks, escalate the dose) once daily in the morning, taken with or without food.
Sponsors
Mayo Clinic
University of Pittsburgh Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18-80 years at the time of enrollment. 2. 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) 3. Able to provide written informed consent and participate in longitudinal follow-up 4. A Stable retinal exam within 1 year prior to enrollment unless new onset diabetes was diagnosed within 6 months prior to study enrollment. If an eye exam within the past year is not available but the most recent exam is stable, a standard of care eye exam needs to be scheduled during the study period. 5. HbA1c level 6.5-10.5% at screening visit. 6. Current ongoing treatment with metformin and/or insulin and other antihyperglycemic medications will be accepted at screening. Patients will be willing to safely withdraw one or more study medication or mealtime insulin under the supervision of the study team by the time of screening. The patients clinical team will be informed promptly. Patients not on any antihyperglycemic medications are also eligible. a. If on a GLP-1 medication (e.g., semaglutide \[Ozempic, Wegovy, Rybelsus\], liraglutide, dulaglutide, exenatide, tirzepatide, etc.), the patient must be on a stable dose for at least 3 months prior to enrollment, with stable weight status at the time of enrollment and the GLP-1 dose cannot be escalated during the study period. 7. Willing to perform blood glucose and ketone testing on study provided meters as per study protocol.
Exclusion criteria
1. 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) 2. Patients on PIO or EMPA at the time of screening 3. Diagnosed with Type 1 Diabetes 4. Pregnancy or lactation in women (positive urine pregnancy test at screening will lead to exclusion) 5. History of bleeding disorders (e.g., Hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), von Willebrand disease, platelet disorders etc) 6. 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 7. Ongoing treatment for any malignancy requiring systemic treatment (non-melanoma skin cancers treated in dermatologists' office would be acceptable) 8. Presence of osteoporosis without definitive treatment according to PI discretion. 9. Recent inflammatory illness within the 30 days preceding enrollment (e.g.: URTI, episode of AP, etc) 10. History of heart failure classified by NYHA as Class III or greater 11. History of kidney dysfunction classified by an eGFR of \<30 mL/min/min 12. Participation in any clinical trial within 30 days before screening for an approved or non-approved investigational medical product. 13. Active alcohol dependence or chemical dependence including tobacco based on investigator discretion 14. On a ketogenic diet 15. Autoimmune pancreatitis, obstructive pancreatitis, and prior surgery of pancreas (Whipple procedure, total pancreatectomy, and distal pancreatectomy) 16. Any condition which could jeopardize participant safety as per investigator opinion, (hemolytic anemia limiting A1c reliability, any evidence of fluid overload, presence of Congestive heart failure etc). 17. Recent DKA or signs of decompensated diabetes in last 6 months or increased β hydroxybutyrate levels (\>0.4 mmol/L) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c (HbA1c) | Baseline to 24 weeks | Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin, or glycates. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin. An HbA1C level below 5.7 percent is considered normal. Reported as percentage of glycated hemoglobin |
| Area under curve (AUC) for glucose | Baseline to 24 weeks | Pre-post study difference in AUC for glucose |
| AUC for C-peptide | Baseline to 24 weeks | Pre-post study difference in AUC for C-Peptide |
| AUC for Insulin | Baseline to 24 weeks | Pre-post study difference in AUC for Insulin |
| AUC for glucagon | Baseline to 24 weeks | Pre-post study difference in AUC for glucagon |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting plasma glucose | Baseline to 24 weeks | Pre-post study difference in Fasting plasma glucose |
| Lean mass | Baseline to 24 weeks | Pre-post study difference in lean mass |
| Fat mass | Baseline to 24 weeks | Pre-post study difference in fat mass |
| Visceral fat | Baseline to 24 weeks | Pre-post study difference in visceral fat |
| Fecal elastase | Baseline to 24 weeks | Pre-post study difference in Fecal elastase (ELISA quantitative test, normal \>200 mcg/g) |
| High Sensitivity C-Reactive Protein (Hs-CRP) | Baseline to 24 weeks | Pre-post study difference in Hs-CRP |
| Total cholesterol, LDL, HDL and Triglyceride | Baseline to 24 weeks | Pre-post study difference in Total cholesterol, LDL, HDL and Triglyceride |
| β-Hydroxybutyrate | Baseline to 24 weeks | Pre-post study difference in β-Hydroxybutyrate |
| Body weight | Baseline to 24 weeks | Pre-post study difference in body weight |
| Blood Pressure | Baseline to 24 weeks | Pre-post study difference in Blood Pressure |
| Body Mass Index (BMI) | Baseline to 24 weeks | Pre-post study difference in BMI |
| Patient-Reported Outcomes Measurement Information System - 29 Profile v2.1 (PROMIS-29 Profile v2.1) | Baseline to 24 weeks | The PROMIS-29 Profile assesses following domains: * Physical function * Pain interference * Anxiety * Depression * Fatigue * Sleep disturbance * Ability to participate in social roles and activities PROMIS-29 is scored using T-scores. Higher T-scores indicate a higher level of the underlying construct. Each domain has a set of questions, typically 4 to 6 items, and responses are rated on a 5-point Likert scale (e.g., "Never," "Rarely," "Sometimes," "Often," "Always" or "Not at all," "A little bit," "Somewhat," etc.). The responses are then scored on a T-score scale (with a mean of 50 and a standard deviation of 10 in the general population). T-scores Interpretation: * A T-score of 50 is the average score for the general population. * T-scores above 50 indicate better functioning or less severe symptoms. * T-scores below 50 indicate worse functioning or more severe symptoms. |
| Insulin sensitivity | Baseline to 24 weeks | Change in sensitivity from baseline vs 24 weeks (Homeostatic Model Assessment, Matsuda Index) |
| Beta cell function | Baseline to 24 weeks | Change in Beta cell function from baseline vs 24 weeks using oral disposition index |
Countries
United States
Contacts
CONTACTRavinder Jeet Kaur, M.B.B.S
PRINCIPAL_INVESTIGATORYogish Kudva
Mayo Clinic
Outcome results
None listed