Intravenous CTLA4-lg Treatment in Recent Onset Type 1 Diabetes Mellitus (TN09)

April 27, 2020 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Effects of CTLA-4 Ig (Abatacept) On The Progression of Type 1 Diabetes In New Onset Subjects

The purpose of this study is to determine whether treatment with CTLA4-Ig (Abatacept) in individuals with new onset T1DM will improve insulin secretion (C-peptide production) compared to placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Type 1 diabetes mellitus (T1DM) is a T-cell mediated autoimmune disease in which insulin-producing beta cells are completely or near completely destroyed resulting in life-long dependence on exogenous insulin.

CTLA4-Ig (Abatacept) inhibits a crucial stimulatory pathway in the activation of T cells. By this mechanism, the drug is thought to arrest or slow the T cell mediated autoimmune destruction of beta-cells and preserve their function. At the time of clinical onset of T1DM, a significant amount of insulin producing beta cells are destroyed, but as many as 10-20% are still capable of insulin production. By using CTLA4-Ig close to the onset of T1DM, we hope to arrest or slow down the autoimmune destruction of these beta-cells and extend the endogenous insulin production. CTLA4-Ig regulates T cell function but does not deplete T cells. Therefore, its safety profile appears to be better than other immunosuppressive agents.

Eligible participants will be randomized to the experimental or control groups. The experimental group will receive intravenous infusions of CTLA-4 Ig. The first infusion will occur at the time of randomization, followed by another infusion 2 and 4 weeks later. Subsequent infusions will be given monthly for two years during the treatment phase of the study. There is a total of 27 infusions during the treatment phase of the study.

Participants in the control group will receive intravenous infusions of placebo according to the same schedule outlined above.

Both groups will receive standard intensive diabetes treatment with insulin and dietary management.

All participants randomized into the study will be seen at study site monthly for 24 months and then every 6 months for up to an additional 2 years. Participants will undergo assessments of their insulin production, immunologic status, overall health and well being and diabetes care.

Study Type

Interventional

Enrollment (Actual)

112

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G-1X8
        • The Hospital for Sick Children
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Childrens Hospital Los Angeles
      • San Francisco, California, United States, 94143
        • University of California - San Francisco
      • Stanford, California, United States, 94305
        • Stanford University
    • Colorado
      • Aurora, Colorado, United States, 80045
        • The Barbara Davis Center for Childhood Diabetes
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of Florida
      • Miami, Florida, United States, 33136
        • University of Miami
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Joslin Diabetes Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • New York
      • New York, New York, United States, 10032
        • Columbia University, Naomi Berrie Diabetes Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh, Children's Hospital of Pittsburgh
    • Texas
      • Dallas, Texas, United States, 75235-8858
        • University of Texas, Southwestern Medical School
    • Washington
      • Seattle, Washington, United States, 98101
        • Benaroya Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 6-45
  2. Within 3 months (100 days) of diagnosis of T1DM based on ADA criteria
  3. At least one diabetes-related autoantibody
  4. Stimulated C-peptide level >0.2 pmol/ml by MMTT conducted 21 days after diagnosis of T1DM and within 37 days of randomization
  5. At least three months from last live immunization received and willing to forgo live vaccinations for three months following last dose of study treatment

Exclusion Criteria:

  1. Immunodeficiency, chronic lymphopenia, active infection, positive PPD result or a history of malignancy
  2. Serologic evidence of current or past HIV, Hepatitis B or C
  3. Pregnancy, lactation, or intention of pregnancy while on study
  4. Current use of immunosuppressive agents, or medications known to influence glucose tolerance or glycemic control
  5. Current participation in another T1DM treatment study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Intravenous infusions of CTLA-4 Ig
Drug: CTLA-4 Ig
Intravenous infusion of 10 mg/kg of CTLA-4 Ig every other week for the first two doses and then every 28 days for a total of 27 doses
Other Names:
  • Abatacept
Placebo Comparator: 2
Intravenous infusions of placebo
Other: Placebo
Intravenous infusions of placebo every other week for the first two doses and then every 28 days for a total of 27 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area Under the Stimulated C-peptide Curve Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 2 Year Visit
Time Frame: 2 years of follow up
The primary outcome is the area under the stimulated C-peptide curve (AUC) based on data collected at time 0 to 2 hours of a 4-hour mixed meal glucose tolerance test (MMTT) conducted at the primary endpoint visit. The timed measurements are done at: 0, 15, 30 60, 90, and 120 minutes.
2 years of follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Juvenile Diabetes Research Foundation
American Diabetes Association

Investigators

  • Principal Investigator: Tihamer Orban, MD, Joslin Diabetes Center
  • Study Chair: Jay Skyler, MD, University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2008

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

July 20, 2007

First Submitted That Met QC Criteria

July 20, 2007

First Posted (Estimate)

July 23, 2007

Study Record Updates

Last Update Posted (Actual)

May 6, 2020

Last Update Submitted That Met QC Criteria

April 27, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TN09 CTLA
  • UC4DK097835 (U.S. NIH Grant/Contract)
  • U01DK061055 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data are available at the NIDDK Central Repository: https://repository.niddk.nih.gov/studies/tn09-ctla4-ig/?query=TN09

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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