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Diabetes Islet Preservation Immune Treatment (DIPIT)

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ClinicalTrials.gov Identifier: NCT02586831
Recruitment Status : Not yet recruiting
First Posted : October 26, 2015
Last Update Posted : December 9, 2019
Sponsor:
Collaborator:
Diabetes Research Institute Foundation
Information provided by (Responsible Party):
Camillo Ricordi and Jay Skyler, University of Miami

Tracking Information
First Submitted Date  ICMJE October 23, 2015
First Posted Date  ICMJE October 26, 2015
Last Update Posted Date December 9, 2019
Estimated Study Start Date  ICMJE July 2020
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
Stimulated C-peptide AUC from a 4-hour MMTT [ Time Frame: 1 Year Visit ]
The primary statistical hypothesis to be assessed in this study is 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02586831 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Diabetes Islet Preservation Immune Treatment
Official Title  ICMJE A Pilot, Safety and Feasibility Trial of Anti-Thymocyte Globulin (ATG), Pegylated Granulocyte Colony Stimulating Factor (GCSF), Low Dose Interleukin-2 (IL-2), Etanercept and Exenatide in the Treatment of New Onset Type 1 Diabetes
Brief Summary 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.
Detailed Description There is a critical need to test therapies that afford long-lasting immunomodulation through the combined use of short courses of depleting agents, more chronic use of drugs that promote immunoregulation and critically control the rebounding effector populations, together with interventions that quell inflammation and support beta cell function and glucose metabolism. Such combined regimens would rely on lower doses of many of these agents, for increased safety and tolerability. Here, we propose a combinatorial regimen based on the administration of drugs that are already FDA approved and marketed, all of which have been used in clinical trials in patients with T1D, alone or in some combination. This trial will test if the regimen proposed, for the first time combining all of these agents, will be successful in preserving insulin secretion in recent onset type 1 diabetes.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes Mellitus, Type 1
  • Hypoglycemia
  • Autoimmune Diseases
  • Diabetes Mellitus
Intervention  ICMJE
  • Drug: Anti-Thymocyte Globulin (ATG)
    Concomitant Drug Administration
    Other Name: Thymoglobulin
  • Drug: Placebo
    Drug Administration
  • Drug: Pegylated GCSF
    Concomitant Drug Administration
    Other Name: Neulasta
  • Drug: Interleukin 2
    Concomitant Drug Administration
    Other Name: Aldesleukin; IL-2 or Proleukin®
  • Drug: Etanercept
    Concomitant Drug Administration
    Other Name: Enbrel®
  • Drug: Exenatide
    Concomitant Drug Administration
    Other Name: Bydureon®
Study Arms  ICMJE
  • Active Comparator: Arm A

    The treatment arm A includes commercially available drugs approved for other indications:

    • Anti-Thymocyte Globulin (ATG or Thymoglobulin®) will be administered at a dose of 2.5mg/kg as two divided IV infusions of 0.5mg/kg and 2mg/kg (day 0 and 1).
    • Pegylated GCSF (Neulasta®) will be administered at a dose of 6mg SC every two weeks for a total of 6 doses (Day 2, 14, 28, 42, 56, and 70).
    • Low-dose Interleukin 2 (Aldesleukin; IL-2 or Proleukin®), 1 million IU/dose will be given SC for 5 consecutive days (days 10-14), and then every two weeks.
    • Etanercept (Enbrel®) will be administered at a dose of 25 mg SC weekly up to 52 weeks.
    • Exenatide (Bydureon®): 2 mg SC weekly up to 52 weeks; Adjust according to symptoms.
    Interventions:
    • Drug: Anti-Thymocyte Globulin (ATG)
    • Drug: Pegylated GCSF
    • Drug: Interleukin 2
    • Drug: Etanercept
    • Drug: Exenatide
  • Placebo Comparator: Arm B
    The subjects randomized in Arm B (control group) will receive respective placebos in a blinded fashion.
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2015)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 35 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rodolfo Alejandro, M.D. (305) 243-5324 ralejand@med.miami.edu
Contact: David A Baidal, M.D. (305) 243-7740 dbaidal@med.miami.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02586831
Other Study ID Numbers  ICMJE 20150856
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Camillo Ricordi and Jay Skyler, University of Miami
Study Sponsor  ICMJE Camillo Ricordi and Jay Skyler
Collaborators  ICMJE Diabetes Research Institute Foundation
Investigators  ICMJE
Principal Investigator: Rodolfo Alejandro, M.D. Diabetes Research Institute, University of Miami
PRS Account University of Miami
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP