Open-label, Multi-centre, Multi-national, Randomized 2-period Crossover Study Comparing Closed-loop Insulin Delivery With Sensor-augmented Pump Therapy Over 4 Months in Children 1-7 Years With Type 1 Diabetes at Home, With an Extension.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 8
- 主要终点
- Time in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)
研究概览
简要总结
The suggested clinical trial is part of the KidsAP project funded by the European Commission's Horizon 2020 Framework Programme and JDRF. It evaluates the use of the Artificial Pancreas (closed loop system) in very young children with type 1 diabetes (T1D) aged 1-7 years. This outcome study aims to determine whether 24/7 automated closed loop glucose control improves time in range compared to sensor augmented pump therapy. An extension phase will evaluate the effect of long-term home use of the 24/7 automated hybrid closed loop insulin delivery system on glucose control (UK sites only).
The study employs an open-label, multi-centre, multi-national, randomized, two-period, crossover design. Participants undergo a 2-4 week run-in period, followed by two 16-week treatment periods (one for each therapy) separated by a 1-4 week washout. The order of treatments is randomized. Up to 80 young children (with a target of 72 randomized subjects) on insulin pump therapy will be recruited from paediatric outpatient diabetes clinics.
Before using the study devices, participants and their parents/guardians receive training on the safe use of the study pump, continuous glucose monitoring (CGM) device, and hybrid closed loop system. Nursery or school carers may also be trained if needed. During the closed loop arm, subjects use the system for 16 weeks under free-living conditions at home and in nursery/school without remote monitoring. In the control arm, subjects use sensor augmented pump therapy for 16 weeks under similar conditions, with regular contact and 24/7 telephone support from the study team.
The primary endpoint is the time spent in the target glucose range (3.9-10.0 mmol/l) as recorded by CGM. Secondary outcomes include the time spent with glucose levels above and below target and other CGM metrics. Safety assessments include the frequency and severity of hypoglycaemic episodes and diabetic ketoacidosis (DKA). In the extension phase, participants have follow-up contacts every 3 months, with the primary endpoint measured over 18 months from the end of the primary phase and compared to sensor augmented pump therapy during that phase. Secondary outcomes, safety, and utility will be assessed similarly.
详细描述
Purpose of clinical trial:
To determine whether 24/7 automated hybrid closed loop will improve glucose control as measured by time within the target range compared with sensor augmented pump therapy in very young children with T1D.
Study objectives:
The study objective is to evaluate the safety, efficacy and utility of automated hybrid closed loop glucose control in very young children with type 1 diabetes.
- EFFICACY: The objective is to assess the ability of a hybrid closed loop system to maintain CGM glucose levels within the target range of 3.9 to 10 mmol/l (70 to 180 mg/dl) in comparison with sensor augmented pump therapy in very young children with type 1 diabetes.
- SAFETY: The objective is to evaluate the safety of closed loop glucose control compared with sensor augmented pump therapy in terms of episodes and severity of hypoglycaemia, frequency of diabetic ketoacidosis (DKA) and nature and severity of other adverse events.
- UTILITY: The objective is to determine the acceptability and duration of use of the closed loop system in this population.
- HUMAN FACTORS: The objective is to assess emotional and behavioural characteristics of participants and parents/guardians and their response to the closed loop system and clinical trial using validated surveys and semi-structured qualitative interviews.
- HEALTH ECONOMICS: The objective is to perform a cost utility analysis to inform reimbursement decision-making.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 7 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 1 and 7 years (inclusive) (Luxembourg and Austria)
- •Age between 2 and 7 years (inclusive) (Germany and UK)
- •Type 1 diabetes as defined by WHO for at least 6 months [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases which 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.).']
- •Insulin pump user (with or without continuous glucose monitoring or flash glucose monitoring system) for at least 3 months, with subject/carer good knowledge of insulin self-adjustment as judged by the investigator
- •On sensor-augmented pump as standard clinical care (extension phase only)
- •Treated with rapid or ultra-rapid acting insulin analogue
- •Subject/carer is willing to perform regular finger-prick blood glucose monitoring, with at least 2 blood glucose measurements taken every day
- •Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
- •Willing to wear glucose sensor
- •Willing to wear closed loop system 24/7 during intervention arm
- •The subject/carer is willing to follow study specific instructions
- •The subject/carer is willing to upload pump and CGM data at regular intervals
排除标准
- •Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- •Untreated coeliac disease or thyroid disease based on local investigations prior to study enrolment
- •Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids
- •Use of closed loop insulin delivery within the past 2 months
- •Known or suspected allergy to insulin
- •Carer's lack of reliable telephone facility for contact
- •Subject/carer's severe visual impairment
- •Subject/carer's severe hearing impairment
- •Medically documented allergy towards the adhesive (glue) of plasters or subject is unable to tolerate tape adhesive in the area of sensor placement
- •Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located in parts of the body which could potentially be used for localisation of the glucose sensor)
- •Sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- •Plan to receive red blood cell transfusion or erythropoietin over the course of study participation
- •Subject/carer not proficient in English (UK, Germany, Austria, Luxembourg) or German (Germany, Austria, Luxembourg) or French (Luxembourg)
- •Additional exclusion criteria - Germany only
- •Known microvascular diabetes complications (retinopathy, renal disease, neuropathy)
- •Eating disorders
- •Psychiatric diseases of the parents that would possibly interfere with the ability to comply to study procedures
- •Major needle phobia that would complicate to wear pump catheter and sensor
- •Congenital malformations that would interfere with diabetes treatment (e.g. congenital heart malformations, lung diseases, renal malformations)
- •Growth hormone deficiency
- •Combined Hypopituitarism
- •Down Syndrome (high risk for comorbidity with coeliac disease, autoimmune thyroiditis)
- •Cancer under treatment
- •Current participation in other interventional clinical trials
研究组 & 干预措施
Automated closed loop insulin delivery (intervention arm)
Unsupervised home use of day and night automated hybrid closed loop insulin delivery system over 16 weeks.
Intervention: Device: CamAPS FX
干预措施: CamAPS FX (Device)
Sensor augmented pump therapy (control arm)
Sensor augmented pump therapy over 16 weeks.
干预措施: Sensor augmented therapy (Other)
结局指标
主要结局
Time in Target (3.9 to 10.0 mmol/l) (70 to 180 mg/dl)
时间窗: 16-week home stay
Between group difference in time spent with sensor glucose levels between 3.9 to 10.0 mmol/l (70 to 180 mg/dl) during the 4 months intervention period.
次要结局
- Time With Glucose Levels in Significant Hyperglycaemia (Glucose Levels > 16.7 mmol/l) (300 mg/dl)(16-week home stay)
- AUC of Glucose Below 3.5 mmol/l (63 mg/dl)(16-week home stay)
- Number of Episodes of Severe Hypoglycaemia(16-week home stay)
- Key Endpoint: Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl)(16-week home stay)
- BMI SDS(16-week home stay)
- Frequency of Diabetic Ketoacidosis(16-week home stay)
- Key Endpoint: HbA1c(16 weeks)
- Key Endpoint: Time Spent Below Target Glucose (3.9 mmol/l) (70 mg/dl)(16-week home stay)
- Coefficient of Variation (Percentage) of Glucose Levels(16-week home stay)
- Time With Glucose Levels <3.0 mmol/l (54 mg/dl)(16-week home stay)
- Total, Basal, and Bolus Insulin Dose(16-week home stay)
- Number of Subjects Experiencing Severe Hypoglycaemia(16-week home stay)
- Key Endpoint: Mean Sensor Glucose(16-week home stay)
- Standard Deviation(16-week home stay)
- Frequency and Nature of Other Adverse Events(16-week home stay)
- Percentage of Time of CGM Availability(16-week home stay)
- Percentage of Time of Closed-loop Operation(16-week home stay)
- Frequency and Nature of Other Serious Adverse Events(16-week home stay)
- Key Endpoint: HbA1c(16-week home stay)
研究者
Dr Roman Hovorka
Study Director
University of Cambridge