Diabetes Islet Preservation Immune Treatment

NCT ID: NCT02586831

Last Updated: 2026-01-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-01

Study Completion Date

2024-06-01

Brief Summary

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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

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Conditions

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Diabetes Mellitus, Type 1 Hypoglycemia Autoimmune Diseases Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Anti-Thymocyte Globulin (ATG)

Intervention Type DRUG

2.5 mg/kg administered as two divided infusions of 0.5 mg/kg and 2 mg/kg on Days 1 and 2.

Interleukin 2

Intervention Type DRUG

1 million IU per dose administered subcutaneously for 5 consecutive days on Days 10-14, and then every two weeks.

Exenatide

Intervention Type DRUG

2 mg administered subcutaneously weekly for up to 52 weeks.

Adalimumab

Intervention Type DRUG

50 mg administered subcutaneously once a month for 1 year.

Arm B

Participants in this group will receive the placebos for Thymoglobulin, Aldesleukin, Adalimumab, Exenatide, and Neulasta over a period of 52 weeks.

Group Type PLACEBO_COMPARATOR

ATG Placebo

Intervention Type OTHER

ATG placebo mimicking Thymoglobulin administered intravenously.

IL-2 Placebo

Intervention Type OTHER

IL-2 placebo mimicking Aldesleukin administered subcutaneously.

Adalimumab Placebo

Intervention Type OTHER

Placebo mimicking Adalimumab administered subcutaneously.

Exenatide Placebo

Intervention Type OTHER

Placebo mimicking Exenatide administered subcutaneously.

Interventions

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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.

Intervention Type DRUG

Interleukin 2

1 million IU per dose administered subcutaneously for 5 consecutive days on Days 10-14, and then every two weeks.

Intervention Type DRUG

Exenatide

2 mg administered subcutaneously weekly for up to 52 weeks.

Intervention Type DRUG

Adalimumab

50 mg administered subcutaneously once a month for 1 year.

Intervention Type DRUG

ATG Placebo

ATG placebo mimicking Thymoglobulin administered intravenously.

Intervention Type OTHER

IL-2 Placebo

IL-2 placebo mimicking Aldesleukin administered subcutaneously.

Intervention Type OTHER

Adalimumab Placebo

Placebo mimicking Adalimumab administered subcutaneously.

Intervention Type OTHER

Exenatide Placebo

Placebo mimicking Exenatide administered subcutaneously.

Intervention Type OTHER

Other Intervention Names

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Thymoglobulin Aldesleukin; IL-2 or Proleukin® Bydureon® HUMIRA®

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Diabetes Research Institute Foundation

OTHER

Sponsor Role collaborator

Camillo Ricordi and Jay Skyler

OTHER

Sponsor Role lead

Responsible Party

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Camillo Ricordi and Jay Skyler

Professors, University of Miami Miller School of Medicine and Director/Deputy Director, Diabetes Research Institute

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Rodolfo Alejandro, M.D.

Role: PRINCIPAL_INVESTIGATOR

Diabetes Research Institute, University of Miami

References

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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.

Reference Type BACKGROUND
PMID: 25998292 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21193733 (View on PubMed)

Other Identifiers

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20150856

Identifier Type: -

Identifier Source: org_study_id

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