Effects of CTLA-4 Ig (Abatacept) On The Progression of Type 1 Diabetes In New Onset Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 13
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
2
Intravenous infusions of placebo
干预措施: Placebo (Other)
1
Intravenous infusions of CTLA-4 Ig
干预措施: CTLA-4 Ig (Drug)
结局指标
主要结局
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
时间窗: 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.
次要结局
未报告次要终点