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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00505375
Recruitment Status : Completed
First Posted : July 23, 2007
Results First Posted : August 16, 2016
Last Update Posted : May 6, 2020
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
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: CTLA-4 Ig Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effects of CTLA-4 Ig (Abatacept) On The Progression of Type 1 Diabetes In New Onset Subjects
Actual Study Start Date : February 2008
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Abatacept

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 Name: 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

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   6 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00505375

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United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
University of California - San Francisco
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Colorado
The Barbara Davis Center for Childhood Diabetes
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0296
University of Miami
Miami, Florida, United States, 33136
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Columbia University, Naomi Berrie Diabetes Center
New York, New York, United States, 10032
United States, Pennsylvania
University of Pittsburgh, Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas, Southwestern Medical School
Dallas, Texas, United States, 75235-8858
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G-1X8
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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
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Principal Investigator: Tihamer Orban, MD Joslin Diabetes Center
Study Chair: Jay Skyler, MD University of Miami
Additional Information:
Publications of Results:
Other Publications:

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Identifier: NCT00505375    
Other Study ID Numbers: TN09 CTLA
U01DK061055 ( U.S. NIH Grant/Contract )
UC4DK097835 ( U.S. NIH Grant/Contract )
First Posted: July 23, 2007    Key Record Dates
Results First Posted: August 16, 2016
Last Update Posted: May 6, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data are available at the NIDDK Central Repository:

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Beta-cell function
treatment of type 1 diabetes
new onset type 1 diabetes
juvenile diabetes
diabetes mellitus
Type 1 diabetes TrialNet
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents