Double-blind, Investigator-initiated Study to Determine the Effect of Alum-GAD (Diamyd) in Combination With Vitamin D3 on the Progression to Type 1 Diabetes in Children With Multiple Islet Autoantibodies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Type 1 Diabetes Month 24
研究概览
简要总结
The purpose of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), in combination with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes in non-diabetic children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.
详细描述
The primary objective of this study is to evaluate if immune-tolerance with Alum-formulated GAD (Diamyd), combined with high dose Vitamin D3, may delay or stop the autoimmune process leading to clinical type 1 diabetes (diagnosed according to American Diabetes Association criteria) in non-diabetic 4-17.99 year old children with ongoing beta-cell autoimmunity as indicated by positive islet autoantibodies.
The secondary objective is to demonstrate that treatment with Diamyd is safe in children at risk for type 1 diabetes.
The children will be followed for 5 years in the study. Primary endpoint is proportion of subjects diagnosed with type 1 diabetes in each treatment arm. Secondary endpoints are 1) safety, 2) change in metabolic status from normal to impaired glucose metabolism in the group of children with normal glucose metabolism at baseline screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children 4-17.99 years of age with positive autoantibodies to glutamate decarboxylase (GADA) and at least one additional type 1 diabetes associated autoantibody (to insulinoma associated protein 2 (IA-2A), Zinktransporter 8 (ZnT8R/Q/WA) or insulin (IAA)).
- •Written informed consent from the child and the childs legal representative(s).
排除标准
- •Ongoing treatment with immunosuppressant therapy.
- •Treatment with any oral or injected anti-diabetic medications
- •Significantly abnormal hematology results at screening.
- •Clinically significant history of acute reaction to vaccines or other drugs
- •Treatment with any vaccine within one month prior to the first dose of the study drug or planned treatment with vaccine up to three months after the last injection with the study drug.
- •A history of epilepsy, serious head trauma or cerebrovascular accident, or Clinical features of continuous motor unit activity in proximal muscles
- •Participation in other Clinical trials with a new chemical entity within the previous 3 months.
- •History of hypercalcemia.
- •Unwilling to abstain from other medication with Vitamin D during the study period.
- •Significant illness within 2 weeks prior to first dosing.
- •Known Human Immuno Deficiency Virus infection or hepatitis.
- •Presence of associated serious disease or condition.
- •Diabetes-protective Human Leucocyte Antigen (HLA) DQ
- •Females who are lactating or pregnant.
- •Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last Diamyd administration.
研究组 & 干预措施
Alum-GAD, Vitamin D3
Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years.
干预措施: Alum-GAD (Drug)
Alum-GAD, Vitamin D3
Two doses à 20 microgram of subcutaneous alum-GAD (Diamyd), 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years.
干预措施: Vitamin D3 (Drug)
Placebo, Vitamin D3
Two doses of subcutaneous placebo, 30 Days apart. Vitamin D 2000 U/Daily with start 30 days before the first injection of Diamyd. Vitamin D treatment will continue throughout the whole study period of 5 years
干预措施: Vitamin D3 (Drug)
结局指标
主要结局
Type 1 Diabetes Month 24
时间窗: 24 months
Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm month 24
Type 1 Diabetes Status Overall
时间窗: Over the entire study period up to 2 years
Number of patients diagnosed with type 1 diabetes according to ADA (American Diabetes Association) criteria in each study arm overall. Including one patient diagnosed shortly after the month 24 visit.
次要结局
- Change From Baseline in GADA Month 1(Month 1)
- Change From Baseline in GADA Month 12(Month 12)
- Number of Patients Developing Impaired Glucose Metabolism Until Month 18(During 18 months follow-up)
- Injection Site Reactions Day 1(Day 1)
- Number of Patients With Progressive Impaired Glucose Metabolism Until Month 18(During 18 months follow-up)
- Injection Site Reactions Month 1(Month 1)
- Change From Baseline in GADA Month 24(Month 24)
研究者
Helena Elding Larsson
Docent, MD, PhD
Lund University