Combination Therapy With Sitagliptin and Lansoprazole to Restore Pancreatic Beta Cell Function in Recent-Onset Type 1 Diabetes (REPAIR-T1D)

Combination Therapy With Sitagliptin (DPP 4 Inhibitor) and Lansoprazole (PPI) Inhibitor) to Restore Pancreatic Beta Cell Function in Recent-Onset Type 1 Diabetes

Sanford Research/USD proposes to study the combination therapy of oral administration of sitagliptin and lansoprazole versus placebo for the preservation of pancreatic beta cells still present in patients with recent-onset diabetes and possibly regenerating their beta cells, while safely down-regulating the autoimmune response directed against the beta cells.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Sitagliptin and Lansoprazole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123-4282
      • Rady Children's Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Children's - St. Paul
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Research/USD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 43 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of type 1 diabetes, based on American Diabetes Association criteria, recently diagnosed (within the 6 months before Screening) and confirmed by the presence of at least 1 diabetes related autoantibody (either glutamic acid decarboxylase [GAD], insulinoma-associated protein [IA 2], or insulin, the latter measured within 10 days after starting insulin therapy).
• Male or female aged between 11 and 45 years, inclusive.
• Able to swallow study capsules.
• Willing to comply with "intensive diabetes management" as directed by the investigator, with the goal of maintaining blood glucose as close to American Diabetes Association recommendations as possible.
• Willing to comply with the schedule of study visits and protocol requirements.

Exclusion Criteria:

• Use of a GLP 1R agonist or DPP 4 inhibitor within 1 month before enrollment.
• Use of a PPI within 1 month before enrollment.
• Use of an oral hypoglycemic agent within 1 month before enrollment or use of thiazolidinediones within 3 months before enrollment (although thiazolidinediones may be used <7days before enrollment).
• Females of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
• Females who are pregnant or breastfeeding at the time of enrollment.

• Subjects with any of the following conditions:

  • Renal insufficiency, defined as estimated glomerular filtration rate (GFR) less than 50 mL/min at Screening, calculated using the Modification of Diet in Renal Disease (MDRD) equation.
  • History of a serious hypersensitivity reaction to sitagliptin or lansoprazole, such as anaphylaxis or angioedema.
  • Severe hepatic insufficiency.
  • History of pancreatitis or gallbladder disease
  • Any significant medical condition, which in the opinion of the investigator or medical monitor would interfere with study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin and Lansoprazole; Sitagliptin 50mg co-administered with Lansoprazole 30mg. Subjects age 11-17 years at Visit 2 will take 1 capsule of each once daily Subjects age 18-45 years at Visit 2 will take 2 capsules of each once daily	Drug: Sitagliptin and Lansoprazole; Sitagliptin (dispensed as 50 mg capsules)and Lansoprazole(dispensed as 30 mg capsules) or matching placebo; Subjects age 11-17 years at Visit 2 will take 1 capsule once daily; Subjects age 18-45 years at Visit 2 will take 2 capsules once daily; Other Names: Januvia; Prevacid
Placebo Comparator: Placebo; Sitagliptin Placebo and Lansoprazole placebo capsules will be administered. Subjects age 11-17 years at Visit 2 will take 1 placebo capsule of each once daily Subjects age 18-45 years at Visit 2 will take 2 placebo capsules of each once daily	Drug: Placebo; Sitagliptin 50mg and Lansoprazole 30 mg or matching placebo will be given daily for 12 months. Subjects age 11-17 at visit 2 will take 1 capsule daily; age 18-45 will take 2 capsules daily.; Other Names: Januvia; Prevacid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 Hour C-peptide AUC in Response to MMTT	Blood samples for C-peptide were collected at baseline (pre-meal) and 15, 30, 60, 90 and 120 minutes post-meal.	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 Hour C-peptide AUC in Response to MMTT	Blood samples for C-peptide were collected at baseline (pre-meal) and 15, 30, 60, 90, and 120 minutes post-meal.	Month 6

Collaborators and Investigators

• Sponsor: Sanford Health
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Alex Rabinovitch, MD, Sanford Research/USD; Study Director: Diane L Hahn, LPN, Sanford Research/USD

Publications and helpful links

General Publications

• Griffin KJ, Thompson PA, Gottschalk M, Kyllo JH, Rabinovitch A. Combination therapy with sitagliptin and lansoprazole in patients with recent-onset type 1 diabetes (REPAIR-T1D): 12-month results of a multicentre, randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2014 Sep;2(9):710-8. doi: 10.1016/S2213-8587(14)70115-9. Epub 2014 Jul 2.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: June 3, 2010
• First Submitted That Met QC Criteria: June 30, 2010
• First Posted (Estimate): July 1, 2010

Study Record Updates

• Last Update Posted (Actual): September 18, 2017
• Last Update Submitted That Met QC Criteria: August 18, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: diabetes; HGB A1C; Beta Cell Regeneration
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Dexlansoprazole; Lansoprazole; Sitagliptin Phosphate
• Other Study ID Numbers: REPAIR-T1D