Randomized, Parallel Group, Dose Escalation Trial of Pioglitazone Versus Empagliflozin for Chronic Pancreatitis/Recurrent Acute Pancreatitis/Acute Pancreatitis Associated Diabetes Mellitus: The PEP-DM Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- Hemoglobin A1c (HbA1c)
研究概览
简要总结
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) or Acute Pancreatitis (AP) 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.
详细描述
This trial will test the efficacy of PIO versus EMPA in improving glycemic control in CP-DM, RAP-DM and DM after one episode AP. The anticipated enrollment will consist of 40 subjects, age 18-80 years who have been diagnosed with CP or RAP or AP 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 or AP associated with DM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18-80 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, or acute pancreatitis followed by diabetes (AP-DM) 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
- •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.
- •HbA1c level 6.5-10.5% at screening visit.
- •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.
- •Willing to perform blood glucose and ketone testing on study provided meters as per study protocol.
排除标准
- •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)
- •Patients on PIO or EMPA at the time of screening
- •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 without definitive treatment according to PI discretion.
- •Recent inflammatory illness within the 30 days preceding enrollment (e.g.: URTI, episode of AP, etc)
- •History of heart failure classified by NYHA as Class III or greater
- •History of kidney dysfunction classified by an 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 (Whipple procedure, total pancreatectomy, and distal pancreatectomy)
- •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).
- •Recent DKA or signs of decompensated diabetes in last 6 months or increased β hydroxybutyrate levels (>0.4 mmol/L) at screening.
研究组 & 干预措施
Pioglitazone (PIO)
PIO (Actos) is a thiazolidinedione and an agonist for peroxisome proliferator activated receptor (PPAR) gamma indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 DM in multiple clinical settings. Its use has limitation for type 1 DM or for treatment of diabetic ketoacidosis. It is contraindicated to use in established NYHA class III or IV heart failure.
干预措施: Pioglitazone (PIO) (Drug)
Empagliflozin (EMPA)
EMPA is a sodium-glucose co-transporter 2 inhibitor, FDA approved drug. It is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, to reduce the risk of cardiovascular death in adults with type 2 DM and established cardiovascular disease and as an adjunct to diet and exercise to improve glycemic control in adults with type 2 DM. It is not recommended in patients with type 1 DM. It may increase the risk of diabetic ketoacidosis. Not recommended for use to improve glycemic control in adults with type 2 DM with an eGFR less than 30mL/min/1.73m2.
干预措施: Empagliflozin (EMPA) (Drug)
结局指标
主要结局
Hemoglobin A1c (HbA1c)
时间窗: 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
时间窗: Baseline to 24 weeks
Pre-post study difference in AUC for glucose
AUC for C-peptide
时间窗: Baseline to 24 weeks
Pre-post study difference in AUC for C-Peptide
AUC for Insulin
时间窗: Baseline to 24 weeks
Pre-post study difference in AUC for Insulin
AUC for glucagon
时间窗: Baseline to 24 weeks
Pre-post study difference in AUC for glucagon
次要结局
- Fasting plasma glucose(Baseline to 24 weeks)
- Fat mass(Baseline to 24 weeks)
- High Sensitivity C-Reactive Protein (Hs-CRP)(Baseline to 24 weeks)
- Body Mass Index (BMI)(Baseline to 24 weeks)
- Total cholesterol, LDL, HDL and Triglyceride(Baseline to 24 weeks)
- Blood Pressure(Baseline to 24 weeks)
- Insulin sensitivity(Baseline to 24 weeks)
- Lean mass(Baseline to 24 weeks)
- Visceral fat(Baseline to 24 weeks)
- Fecal elastase(Baseline to 24 weeks)
- β-Hydroxybutyrate(Baseline to 24 weeks)
- Body weight(Baseline to 24 weeks)
- Patient-Reported Outcomes Measurement Information System - 29 Profile v2.1 (PROMIS-29 Profile v2.1)(Baseline to 24 weeks)
- Beta cell function(Baseline to 24 weeks)
研究者
Yogish C. Kudva
Principal Investigator
Mayo Clinic