A Phase I Trial of Proleukin and Rapamune in Recent-onset Type 1 Diabetes Mellitus (ITN018AI)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 3
- 主要终点
- Incidence and severity of adverse events and laboratory anomalies
研究概览
简要总结
This is a phase I trial in individuals who have been diagnosed with type 1 diabetes within the previous 3-48 months. The study is testing whether two immune system modifying drugs are safe when used in combination and if they have immune altering effects that indicate they can halt the progression of type 1 diabetes progression.
详细描述
At the time of diagnosis with type 1 diabetes, 15-40% of beta cells may remain active and healthy in the pancreas, capable of producing insulin the body needs to regulate blood glucose levels. Because even small amounts of natural insulin production can decrease the long term effects of diabetes, it is essential that these cells are preserved.
This trial will test whether a combination of the drugs Proleukin (IL-2) and Rapamune (sirolimus) may be safely administered to recently diagnosed type 1 diabetes patients and whether it causes changes to the immune system that can halt the autoimmune destruction of the remaining beta cells. This drug combination has been found to be effective for long-term diabetes prevention in mouse models of type 1 diabetes.
This study is a phase I study for individuals 18-45 years of age who have been diagnosed with type 1 diabetes in the past 3-48 months. All participants will be treated with Proleukin (administered subcutaneously 3x per week) for 28 days and Rapamune (taken orally, daily) for 12 weeks. The study will last for 12 months, with additional follow-up of 24 months. The majority of study visits occur within the first 6 months. Mixed meal tolerance tests, in which participants take a milkshake-like drink and have blood sampled over a 2 or 4-hour period, will take place during an initial screening visit and three additional times during the first year. All participants will also receive intensive diabetes management designed to maintain stable blood glucose levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with type 1 diabetes (per ADA criteria) more than 3 but less than 48 months prior to enrollment;
- •18 to 45 years of age;and
- •Positive for at least one islet cell autoantibody (GAD65-antibody, CA512-antibody and/or ICA).
排除标准
- •Chronic use of glucocorticoids or other immunosuppressive ages 4 weeks before enrollment;
- •History of recurrent infections, other autoimmune diseases, cardiac disease, cataracts or other chronic medical conditions that investigators believe could compromise participant safety;
- •Females who are pregnant, lactating intend to get pregnant, or are unwilling to undergo pregnancy testing during the study;
- •Males who intend to father a pregnancy during the first 6 months of the study; or
- •Participation in another clinical study within the last 30 days.
研究组 & 干预措施
Rapamycin/IL-2 combination therapy
IL-2 (Proleukin) was administered at 4.5 3 106 IU s.c., three times per week for 4 weeks for a total of 12 doses. Rapamycin (Rapamune or Sirolimus) was administered without a loading dose at 2 mg/day, with adjustments to maintain trough blood levels of 5-10 ng/mL for 3 months.
干预措施: IL-2 (Drug)
Rapamycin/IL-2 combination therapy
IL-2 (Proleukin) was administered at 4.5 3 106 IU s.c., three times per week for 4 weeks for a total of 12 doses. Rapamycin (Rapamune or Sirolimus) was administered without a loading dose at 2 mg/day, with adjustments to maintain trough blood levels of 5-10 ng/mL for 3 months.
干预措施: Rapamycin (Drug)
结局指标
主要结局
Incidence and severity of adverse events and laboratory anomalies
时间窗: through day 364
次要结局
- Insulin dose in units per kilogram(various)
- AUC for C-peptide responses following MMTT(various)
- Frequency of severe hypoglycemia(various)
- HbA1c levels(various)