Anti-IL-1 Treatment in Children Diabetic Keto-Acidosis (DKA) at Diagnosis of Type 1 Diabetes.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Frequency of Adverse Events
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled phase 2 study. Specific aim is to evaluate feasibility and safety of anti-IL-1 (interleukin 1) treatment in the course of standard therapy for diabetic ketoacidosis in children and its effect on intracranial pressure.
详细描述
Anakinra is a fully human IL-1ra (interleukin 1 receptor agonist) licensed in 2001 by FDA for the treatment of rheumatoid arthritis. It competitively binds to the IL-1 receptor, thus blocking IL-1 signaling. It is a short-acting agent that requires daily subcutaneous administration at 1-2 mg/kg, maximum 100 mg/dose. It has been effective in lowering HbA1c (glycated haemoglobin) in T2D (type 2 diabetes) and a randomized trial of anakinra in recent onset T1D (type 1 diabetes) is underway in Europe. Overall, anakinra has been used in adults and children with a good safety record, for more than 10 years. Infrequent side effects include infections, neutropenia, nausea, diarrhea, cardiopulmonary arrest, influenza-like symptoms, and production of anti-anakinra antibodies.
Study Design: A double-blinded placebo-controlled RCT (randomized controlled trial) with 2:1 allocation (14 active treatment vs. 7 placebo). Anakinra treatment will be given as a bolus of 2 mg/kg infused intravenously over 30 minutes followed by infusion of 2 mg/kg/hour for 4 hours immediately after confirmation of the diagnosis of DKA (diabetic keto-acidosis) and when laboratory safety parameters are available (CBC (complete blood count) and pregnancy test) and after a consent is obtained. Primary outcomes: Safety and tolerability of anti-IL-1 treatment (anakinra) during the initial 24 hr period of DKA treatment. Secondary outcomes: Optic nerve sheath diameter (cut-off to define cerebral edema: 4.5 mm); Changes in cytokines levels during the treatment with anakinra.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 8-18 years at diagnosis of type 1 diabetes
- •Diabetic ketoacidosis with:
- •plasma glucose concentration >300 mg/dl,
- •venous pH <7.30 or
- •serum bicarbonate concentration <15 mmol/L, and
- •ketones in urine or serum
- •Hematology:
- •WBC >3000 x 109/L;
- •platelets >100,000 x 109/L;
- •hemoglobin >10.0 g/dL
- •Negative blood pregnancy test in females.
排除标准
- •Children with underlying disorders, including:
- •active autoimmune or immune deficiency disorder other than type 1 diabetes,
- •malignancy,
- •organ transplant,
- •any condition requiring chronic corticosteroid use
- •Previous immunotherapy to prevent type 1 diabetes
- •Current or prior infection with HIV, hepatitis B or hepatitis C assessed by history
- •Patients who present with DKA concomitant with alcohol or drug use,
- •Head trauma,
- •Meningitis or other conditions which might affect neurological function
- •Renal failure
- •Any condition, medical or otherwise that would, in the opinion of the investigator, prevent complete participation in the study, or that would pose a significant hazard to the subject's participation
- •Patients with a history of known hypersensitivity to:
- •E coli-derived proteins,
- •anakinra, or
- •any components of the investigational drug product
研究组 & 干预措施
Active Treatment
14 subjects with receive active treatment with Anakinra.
干预措施: Anakinra (Drug)
Placebo
7 subjects will receive the placebo comparator.
干预措施: Placebo Comparator (Other)
结局指标
主要结局
Frequency of Adverse Events
时间窗: 24 hours
Type and number of Adverse Events related to anti-IL-1 treatment (anakinra) during the initial 24 hour period of DKA treatment.
次要结局
未报告次要终点