Diabetes Islet Preservation Immune Treatment (DIPIT)

A Pilot, Safety and Feasibility Trial of Anti-Thymocyte Globulin (ATG), Low Dose Interleukin-2 (IL-2), Adalimumab and Exenatide in the Treatment of New-Onset Type 1 Diabetes

To assess whether there is a difference in endogenous insulin secretion, measured as stimulated C-peptide secretion (area under the curve during a 4-hour mixed meal tolerance test), at the 1 year visit, for study subjects receiving combinational therapy versus those receiving placebo. The study will also examine the effect of the proposed treatments on immunological outcomes, specifically proportion of regulatory T cells at the 1 year visit.

Study Overview

• Status: Not yet recruiting
• Conditions: Autoimmune Diseases; Diabetes Mellitus; Hypoglycemia; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: Anti-Thymocyte Globulin (ATG); Drug: Interleukin 2; Drug: Exenatide; Drug: Adalimumab; Other: ATG Placebo; Other: IL-2 Placebo; Other: Adalimumab Placebo; Other: Exenatide Placebo

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: David A Baidal, M.D.; Phone Number: (305) 243-7740; Email: dbaidal@med.miami.edu
• Study Contact Backup: Name: Rodolfo Alejandro, M.D.; Phone Number: (305) 243-5324; Email: RAlejand@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Diabetes Research Institute, University of Miami Miller School of Medicine
      • Contact: Rodolfo Alejandro, M.D.; Phone Number: 305-243-5324; Email: ralejand@med.miami.edu
      • Contact: David A Baidal, M.D.; Phone Number: (305) 243-7740; Email: dbaidal@med.miami.edu
      • Principal Investigator: Rodolfo Alejandro, M.D.
      • Principal Investigator: David A Baidal, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must meet all of the following criteria to be eligible to participate in this study:

  1. Subject must be able to understand and provide informed consent.
  2. Males and females, 18-35 years of age.
  3. New onset T1D for no longer than 120 days at the time of randomization.
  4. Affected by T1D, according to ADA standard criteria, and confirmed by positivity of at least one T1D-associated autoantibody, to GAD65, IA-2, ZnT8, or insulin autoantibodies (if patient has been treated with insulin for less than 2 weeks).
  5. Being on insulin therapy.
  6. Stimulated C-peptide peak level >0.2 nmol/L at the baseline 1 visit MMTT.
  7. Female subjects of childbearing potential must have a negative pregnancy test upon study entry.
  8. Female (and male) subjects with reproductive potential must agree to use two FDA approved methods of birth control for the entire duration of the study.
  9. Adequate venous access to support study required blood draws.

Exclusion Criteria:

• Potential participants must not meet any of the following exclusion criteria:

  1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
  2. BMI>30 Kg/m2.
  3. Contra-indications to ATG, GCSF, exenatide, etanercept and IL-2 (as per package insert, e.g., knowledge of hypersensitivity to drugs or its excipients).
  4. Uncompensated heart failure, fluid overload, myocardial infarction or liver disease or severe impairment of a vital organ within the last 6 weeks before enrollment.
  5. Any of the following laboratory findings: hemoglobin <10.0 g/dL; leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets <100,000/μL.
  6. Any sign or diagnosis of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, or CMV), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, IGRA test for TB, or hepatitis B-C).
  7. Ongoing acute infections, e.g., acute respiratory tract urinary tract, or gastrointestinal tract infections.
  8. Ongoing or anticipated use of diabetes medications other than insulin.
  9. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within prior 7 days of screening.
  10. Current or prior use of immunomodulators or systemic steroids in the last 2 months that could potentially affect diabetes or immunologic status.
  11. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 6 weeks of randomization.
  12. Use of investigational drugs within 3 months of participation.
  13. Concomitant therapy with immunosuppressive drugs, immunomodulators, or cytotoxic agents, or previous therapy less than 3 months from randomization.
  14. History or diagnosis of malignancy. Any history of gastroparesis or other severe gastrointestinal disease, pancreatitis, thyroid nodules or malignancy with the exception of a history of localized basal cell carcinoma.
  15. Presence of an allograft.
  16. AST, ALT or Alkaline Phosphatase >2 times upper limit of normal or total bilirubin >1.5 times upper limit of normal.
  17. Current, diagnosed, mental illness or current, diagnosed or self-reported drug or alcohol abuse; or any situation that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
  18. Pregnancy or ongoing breastfeeding for women; unwillingness or inability of both females and males of childbearing age to use a reliable and effective form of contraception, for the entire duration of the study.
  19. Past or current medical problems, or findings from physical examination, or laboratory testing, that are not listed above which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained.

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: Arm A; Participants in this group will receive Thymoglobulin, Aldesleukin, Adalimumab, and Exenatide over a period of 52 weeks.; Anti-Thymocyte Globulin (ATG or Thymoglobulin®) will be administered at a dose of 2.5mg/kg (2 infusions, 0.5 and 2mg/kg) Days 1 and 2; Adalimumab (Humira®) will be administered at a dose of 50 mg every month, for 1 year; Low-dose Interleukin 2 (Aldesleukin; IL-2 or Proleukin®) will be administered 1 million IU/dose; 5 consecutive days (days 10-14), & then every 2 weeks, for 52 weeks; Exenatide (Bydureon®): 2 mg SC weekly up to 52 weeks.	Drug: Anti-Thymocyte Globulin (ATG); 2.5 mg/kg administered as two divided infusions of 0.5 mg/kg and 2 mg/kg on Days 1 and 2.; Other Names: Thymoglobulin; Drug: Interleukin 2; 1 million IU per dose administered subcutaneously for 5 consecutive days on Days 10-14, and then every two weeks.; Other Names: Aldesleukin; IL-2 or Proleukin®; Drug: Exenatide; 2 mg administered subcutaneously weekly for up to 52 weeks.; Other Names: Bydureon®; Drug: Adalimumab; 50 mg administered subcutaneously once a month for 1 year.; Other Names: HUMIRA®
Placebo Comparator: Arm B; Participants in this group will receive the placebos for Thymoglobulin, Aldesleukin, Adalimumab, Exenatide, and Neulasta over a period of 52 weeks.	Other: ATG Placebo; ATG placebo mimicking Thymoglobulin administered intravenously.; Other: IL-2 Placebo; IL-2 placebo mimicking Aldesleukin administered subcutaneously.; Other: Adalimumab Placebo; Placebo mimicking Adalimumab administered subcutaneously.; Other: Exenatide Placebo; Placebo mimicking Exenatide administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Simulated C-peptide AUC	Endogenous insulin secretion as measured as stimulated C-peptide section Area Under the Curve (AUC) during a 4 hour mixed meal tolerance test (MMTT)	1 Year Visit
Proportion of regulatory T cells	As measured from blood samples	1 Year Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1c (HbA1c) levels	Measure of glycemic control as evaluated by HbA1c levels from blood samples	Up to 18 months
Insulin dose	Measure of glycemic control as evaluated by insulin dose	Up to 18 months
Mean daily plasma glucose levels	Measure of glycemic control as evaluated by the mean daily plasma glucose levels from blood samples	Up to 18 months
Incidence of immune response adverse events	Incidence of immune response adverse events as assessed by treating physician	Up to 18 months

Collaborators and Investigators

• Sponsor: Camillo Ricordi and Jay Skyler
• Collaborators: Diabetes Research Institute Foundation
• Investigators: Principal Investigator: Rodolfo Alejandro, M.D., Diabetes Research Institute, University of Miami

Publications and helpful links

General Publications

• Skyler JS. Prevention and reversal of type 1 diabetes--past challenges and future opportunities. Diabetes Care. 2015 Jun;38(6):997-1007. doi: 10.2337/dc15-0349.
• Skyler JS, Ricordi C. Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man. Diabetes. 2011 Jan;60(1):1-8. doi: 10.2337/db10-1114. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: October 23, 2015
• First Submitted That Met QC Criteria: October 23, 2015
• First Posted (Estimated): October 26, 2015

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia; Autoimmune Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Tumor Necrosis Factor Inhibitors; Aldesleukin; Adalimumab; Exenatide; Thymoglobulin; Antilymphocyte Serum; Interleukin-2
• Other Study ID Numbers: 20150856

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No