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

This study has been completed.
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
American Diabetes Association
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00505375
First received: July 20, 2007
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Type 1 Diabetes Mellitus
Drug: CTLA-4 Ig
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Effects of CTLA-4 Ig (Abatacept) On The Progression of Type 1 Diabetes In New Onset Subjects

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Insulin production (C-peptide secretion) [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HbA1c [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
  • Number and severity of hypoglycemic events [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
  • Immunologic outcomes [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]

Enrollment: 112
Study Start Date: February 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   6 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00505375

Locations
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
Juvenile Diabetes Research Foundation
American Diabetes Association
Investigators
Principal Investigator: Tihamer Orban, MD Joslin Diabetes Center
Study Chair: Jay Skyler, MD University of Miami
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00505375     History of Changes
Other Study ID Numbers: CTLA (IND)
Study First Received: July 20, 2007
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
DPT-1
treatment of type 1 diabetes
new onset type 1 diabetes
juvenile diabetes
T1D
diabetes mellitus
Type 1 diabetes TrialNet
CTLA4-Ig
Abatacept
Beta-cell function
T-cells
treatment
TrialNet

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014