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

Phase 2

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: CTLA-4 Ig; Other: Placebo

• Registration Number: NCT00505375
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary

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.

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 Timeline

• Study First Submitted: 2007-07-20
• Study First Submitted QC: 2007-07-20
• Study First Posted: 2007-07-23
• Study Start: 2008-02
• Primary Completion: 2012-05
• Study Completion: 2012-05
• Results First Submitted: 2016-05-12
• Results First Submitted QC: 2016-07-07
• Results First Posted: 2016-08-16
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-27
• Last Update Posted: 2020-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	CTLA-4 Ig	Intravenous infusions of CTLA-4 Ig
2	Placebo	Intravenous infusions of placebo

Primary Outcome Measures

Name	Time	Method
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	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.

Trial Locations

Locations (13)

Childrens Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Benaroya Research Institute; 🇺🇸 Seattle, Washington, United States

University of Miami; 🇺🇸 Miami, Florida, United States

The Barbara Davis Center for Childhood Diabetes; 🇺🇸 Aurora, Colorado, United States

University of Pittsburgh, Children's Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Joslin Diabetes Center; 🇺🇸 Boston, Massachusetts, United States

University of California - San Francisco; 🇺🇸 San Francisco, California, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Columbia University, Naomi Berrie Diabetes Center; 🇺🇸 New York, New York, United States

Stanford University; 🇺🇸 Stanford, California, United States

University of Texas, Southwestern Medical School; 🇺🇸 Dallas, Texas, United States

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada