Intravenous CTLA4-lg Treatment in Recent Onset Type 1 Diabetes Mellitus
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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 |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.
| 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 |
- Insulin production (C-peptide secretion) [ Time Frame: 2 years of follow up ] [ Designated as safety issue: No ]
- 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 ]
| Estimated Enrollment: | 108 |
| Study Start Date: | February 2008 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | February 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 |
Inclusion Criteria:
- Age 6-45
- Within 3 months (100 days) of diagnosis of T1DM based on ADA criteria
- At least one diabetes-related autoantibody
- Stimulated C-peptide level >0.2 pmol/ml by MMTT conducted 21 days after diagnosis of T1DM and within 37 days of randomization
- 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:
- Immunodeficiency, chronic lymphopenia, active infection, positive PPD result or a history of malignancy
- Serologic evidence of current or past HIV, Hepatitis B or C
- Pregnancy, lactation, or intention of pregnancy while on study
- Current use of immunosuppressive agents, or medications known to influence glucose tolerance or glycemic control
- Current participation in another T1DM treatment study
Contacts and 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 | |
| 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: | Tihamer Orban, MD, Joslin Diabetes Center |
| ClinicalTrials.gov Identifier: | NCT00505375 History of Changes |
| Other Study ID Numbers: | CTLA (IND) |
| Study First Received: | July 20, 2007 |
| Last Updated: | January 31, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
|
CTLA4-Ig Abatacept Beta-cell function T-cells DPT-1 treatment treatment of type 1 diabetes |
new onset type 1 diabetes juvenile diabetes T1D diabetes mellitus Type 1 diabetes TrialNet TrialNet |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Autoimmune Diseases Immune System Diseases Cytotoxic T-lymphocyte antigen 4 |
Abatacept Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 16, 2013