Clinical Investigation of Efficacy of Tauroursodeoxycholic Acid (TUDCA) to Enhance Pancreatic Beta Cell Survival In Type 1 Diabetes by Reducing Endoplasmic Reticulum Stress
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in C-peptide Measurement as Reflection of Insulin Secretion at 6 Months
研究概览
简要总结
Clinically, the ability to slow or prevent beta cell demise can prevent or improve the course of type 1 diabetes. The immune-mediated destruction of beta cells that is an apparent major pathological basis for the disease, has led to efforts to prevent or suppress this immune assault. Here the investigators propose to buttress the beta cell's capacity to withstand this assault by improving the function of the endoplasmic reticulum stress resolving mechanisms within these cells. The ability to do so could have a major impact on preventive and therapeutic strategies for type 1 diabetes (and possibly other types of diabetes). The type of endoplasmic reticulum stress relieving agent (TUDCA) proposed here could ultimately be applied on an anticipatory basis to individuals at high risk for type 1 diabetes.
详细描述
Reducing endoplasmic reticulum stress will promote beta cell survival in new-onset type 1 diabetes.
The primary aim is to test the clinical efficacy of an already approved agent, TUDCA, re-purposed to reduce endoplasmic reticulum stress and improve beta cell survival in patients with new onset type 1 diabetes. The primary endpoint of this proposed double-blinded randomized placebo-controlled pilot study is c-peptide measured after mixed meal stimulation test at randomization and then at 6 and 12 months of treatment with TUDCA compared to treatment with placebo and at 6 months following treatment.
TUDCA is an oral medication with a safety profile that is approved for use in Europe for gall stones and liver disease. The drug and similar compounds has been used in children, as young as newborns, and in adults. TUDCA's ability to lower endoplasmic reticulum stress has only recently been recognized and will be applied to new-onset type 1 diabetes in this proposal. If this pilot trial is successful, future studies could include broadening the recipients to antibody-positive pre-type 1 diabetes patients and/or combining TUDCA with other agents shown to have a beneficial effect on insulin secretion in new-onset type 1 diabetes.
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
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes according to American Diabetes Association criteria
- •Diagnosis of type 1 diabetes within 100 days of randomization
- •One positive diabetes-related autoantibody
- •Ages 18-45 years
排除标准
- •Drugs known to affect glucose other than insulin
- •Stimulated C-peptide levels < 0.2 pmol/ml measured during a mixed meal tolerance test conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization to either TUDCA or placebo.
- •Women during pregnancy
研究组 & 干预措施
Taurourodeoxycholic Acid (TUDCA)
TUDCA 1750 mg/day x 12 months
干预措施: Tauroursodeoxycholic Acid (TUDCA) (Drug)
Sugar pill (placebo)
Placebo at same dose, frequency, and duration as experimental treatment
干预措施: Sugar Pill (placebo) (Drug)
结局指标
主要结局
Change in C-peptide Measurement as Reflection of Insulin Secretion at 6 Months
时间窗: Baseline and 6 months
The primary endpoint will be the change from baseline in area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at 6 months.
Change in C-peptide Measurement as Reflection of Insulin Secretion at 12 Months
时间窗: Baseline and 12 months
The primary endpoint will be the change from baseline in area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at 12 months.
Change in C-peptide Measurement as Reflection of Insulin Secretion at 18 Months
时间窗: Baseline and 18 months
The primary endpoint will be the change from baseline in area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at 18 months
次要结局
- Number of Participants With Liver Function Test Abnormalities(18 months)
- Change in Insulin Use at 6 Months(Baseline and 6 months)
- Change in Insulin Use at 12 Months(Baseline and 12 months)
- Change in Insulin Use at 18 Months(Baseline and 18 months)
- Change in HbA1c at 6 Months(Baseline and 6 months)
- Change in HbA1c at 12 Months(Baseline and 12 months)
- Change in HbA1c at 18 Months(Baseline and 18 Months)
研究者
Robin Goland, MD
J. Merrill Eastman Professor of Clinical Diabetes, Co-Director, Berrie Center
Columbia University