A Randomised Clinical Trial of the Effect of Interleukin-1 Receptor Antagonism on the Insulin Production in Patients With New Onset Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 17
- 主要终点
- Δ 2-h AUC C-peptide response
研究概览
简要总结
A draw trial of the effect of Interleukin-1 Receptor Antagonist (anakinra, Kineret®) on the insulin production in patients with new onset Type 1 diabetes.
Kineret® is already being used in the treatment of patients suffering from rheumatoid arthritis and preclinical studies are now suggesting that it may also be useful for patients with Type 1 diabetes. The active substance in Kineret is interleukin-1 receptor antagonist, a blocker of an immune-signal molecule named interleukin-1.
The trial is a blinded randomised trial, in which the patient is allocated to receive the active drug (Kineret®) or placebo (saline). The hypothesis is that anti-IL-1 treatment as add-on therapy to conventional insulin therapy will preserve or enhance beta-cell function.
详细描述
Objectives:
The aim of the Anti-Interleukin-1 in Diabetes Action trial (AIDA) study is to test the feasibility, safety/tolerability and potential efficacy of anti-IL-1 therapy in maintaining or enhancing beta-cell function in people with new onset Type 1 diabetes.
Trial Design:
A randomized, placebo controlled, double masked, parallel group, multicentre trial of IL-1 antagonism in subjects with newly-diagnosed Type 1 diabetes. Patients are instructed to inject 100 mg human recombinant interleukin-1 receptor antagonist (anakinra, Kineret®, Amgen, CA) or placebo s.c. once daily for 2 years. Endpoints will be evaluated every three months, with an interim analysis after 6 months.
Trial population:
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 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 1 diabetes diagnosed according to WHO 1999 criteria
- •Positive GAD auto-antibodies
- •Age 18-35 yrs at onset of diabetes
- •Time from first symptoms of diabetes < 12 weeks
- •Peak C-peptide more than or equal to 200 pM after a standardized mixed meal test (Boost) at a test carried out when the subject is metabolically stable, i.e. after resolution of any polyuria, polydypsia or ketoacidosis.
排除标准
- •Severe liver or renal disease (creatinine > 100 μmol/L, ASAT/ALAT > 2* ULN, alkaline phosphatase > 2 * ULN)
- •History of heart disease, signs of cardiac failure or abnormal ECG
- •Present or previous malignancy
- •Pregnancy or failure of fertile female to comply with contraceptional planning, or breast-feeding. (Safe contraceptive methods include birth control pills, IUD, and gestagen implants) . Plans of pregnancy within 2 years.
- •Participation in other clinical intervention studies
- •Anti-inflammatory therapy (except aspirin £ 100 mg/d)
- •Active infections (CRP>30), history of recurrent infection or predisposition to infections
- •Neutropenia: ANC < 1.5*109/L, or anaemia: Haemoglobin < 8.0 g/dL
- •Immune-suppressive treatment or immune-deficiency
- •Presence at diagnosis of late diabetic complications
- •Concurrent vaccination with live vaccine. Known need for live vaccinations within 2 years.
- •Use of Etanercept within 6 months before screening or during the double-blinded study period
- •Hypersensitivity to E. coli-derived proteins, anakinra or any components of the product.
研究组 & 干预措施
2
The patients are instructed to administer placebo by subcutaneous injection
干预措施: saline (Drug)
1
The patients are instructed to administer anti-IL-1 therapy in the form of recombinant human non-glycosylated interleukin-1 receptor antagonist (IL-1Ra, anakinra, Kineret®, Amgen, CA, USA) [13] at a dose of 100 mg once daily by subcutaneous injection
干预措施: anakinra (Drug)
结局指标
主要结局
Δ 2-h AUC C-peptide response
时间窗: 1 month, 3 months, 6 months, 9 months
次要结局
- Incremental and/or peak C-peptide response, Time to peak C-peptide, insulin requirement per kg body weight per day,frequency of insulin free state with maintenance of HbA1c <7.5%, HbA1c, Means of fasting glucose values, circulating IL-6 and CRP(1 month, 3 months, 6 months, 9 months)
研究者
Lise Tarnow
professor
Steno Diabetes Center Copenhagen