An Open-label, Multicentre, Randomised, Single-period, Parallel Design Study to Assess the Effect of Closed Loop Insulin Delivery From Onset of Type 1 Diabetes in Youth on Residual Beta Cell Function Compared to Standard Insulin Therapy
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 96
- 试验地点
- 14
- 主要终点
- Area under the meal stimulated C-peptide curve (AUC) during a mixed meal tolerance test (MMTT)
研究概览
简要总结
The purpose of the study is to use a novel treatment approach, the artificial pancreas, after diagnosis of type 1 diabetes (T1D) to improve glucose control with the anticipated improvements of residual C-peptide secretion.
This is an open-label, multicentre, single-period, randomised, parallel group design study. It is expected that a total of up to 190 subjects (aiming for 96 randomised subjects) will be recruited within ten working days of diagnosis of type 1 diabetes through paediatric diabetes centres in the UK. Half of the participants aged 10 to 16.9 years will be treated by conventional insulin injections and the other half by the artificial pancreas (closed loop insulin delivery system). Each treatment will last 24 months. All participants completing the 24 month study period will be invited to continue in an optional extension phase with the treatment allocated at randomisation for a further 24 months.
Subjects in the intervention group will receive additional training on components of the artificial pancreas, i.e. insulin pump and continuous glucose monitoring (CGM), prior to starting closed loop insulin delivery. Subjects in the control intervention group will continue with standard therapy, i.e. multiple daily injection therapy. The study includes up to 14 visits and 1 telephone/email contact for subjects completing the study. After run-in and randomisation, visits will be conducted every 3 months in both arms. Beta-cell function will be assessed by serial measurement of C-peptide in response to a standardised mixed meal tolerance test (MMTT). MMTTs will be conducted at baseline, 6-,12- and 24 months post diagnosis.
The primary outcome is the between group difference in the area under the stimulated C-peptide curve (AUC) of the MMTT at 12 month post diagnosis. Secondary outcomes include between group differences in stimulated C-peptide AUC over 24 months, differences in glycaemic control as assessed by HbA1c, time spent in glucose target range, glucose variability, hypo- and hyperglycaemia as recorded by periodically applied CGM, as well as insulin requirements and change in bodyweight. Additionally, cognitive, emotional and behavioural characteristics of participating subjects and parents will be assessed, and a cost utility analysis on the benefits of closed loop insulin delivery will be performed. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes, diabetic ketoacidosis (DKA) and number, nature and severity of other adverse events.
详细描述
Purpose of the study:
- To determine whether continued intensive metabolic control using closed loop insulin delivery (CL) following diagnosis of type 1 diabetes can preserve C-peptide secretion as a marker of residual beta cell function compared to standard multiple daily injections (MDI) therapy
Primary objective:
- To assess residual C-peptide secretion 12 months after diagnosis of type 1 diabetes in participants receiving either CL insulin delivery or standard MDI therapy
Secondary Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 16 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 1 diabetes within previous 21 days. Day 1 will be defined as the day insulin was first administered. Type 1 diabetes will be defined according to WHO criteria using standard diagnostic practice.
- •[WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).']
- •The subject is at least 10 years and not older than 16.9 years
- •The subject/carer is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day
- •The subject is literate in English
- •The subject is willing to wear glucose sensor
- •The subject is willing to wear closed loop system at home
- •The subject is willing to follow study specific instructions
- •The subject is willing to upload pump and CGM data at regular intervals
排除标准
- •Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- •Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
- •Known or suspected allergy to insulin
- •Regular use of acetaminophen
- •Lack of reliable telephone facility for contact
- •Pregnancy, planned pregnancy, or breast feeding
- •Living alone
- •Severe visual impairment
- •Severe hearing impairment
- •Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
- •Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor
- •Illicit drugs abuse
- •Prescription drugs abuse
- •Alcohol abuse
- •Sickle cell disease, haemoglobinopathy, receiving red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- •Eating disorder such as anorexia or bulimia
- •Milk protein allergy
结局指标
主要结局
Area under the meal stimulated C-peptide curve (AUC) during a mixed meal tolerance test (MMTT)
时间窗: 12 months post diagnosis
次要结局
- Standard deviation of sensor glucose levels(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Coefficient of variation of sensor levels(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Percentage of time with sensor glucose levels <3.5 mmol/l and <2.8 mmol/l(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- AUC of sensor glucose below 3.5mmol/l(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Time with sensor glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/l)(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Blood pressure(Baseline, 6, 12 and 24 months post diagnosis)
- Insulin Requirements(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Percentage of patients in each group with HbA1c <7.5% (58mmol/mol)(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Percentage of time spent below target glucose (3.9mmol/l)(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Lipid profile(Baseline, 12 and 24 months post diagnosis)
- Mean stimulated C-peptide AUC during a mixed meal tolerance test(Baseline, 6 months and 24 months post diagnosis)
- Percentage of time spent with sensor glucose readings in the target range (3.9 to 10mmol/l)(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Mean sensor glucose level(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Time spent with sensor glucose above target (10.0 mmol/l)(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
- Weight(Baseline, 6, 12 and 24 months post diagnosis)
- HbA1c Levels(Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis)
研究者
Dr Roman Hovorka
Director of Research
University of Cambridge