An Open-label, Multi-centre, Randomised, Single-period, Parallel Design Study to Assess the Efficacy, Safety, Utility and Psychosocial Effect of 12 Week Day and Night Automated Closed Loop Glucose Control Combined With Pump Suspend Feature Compared to Sensor Augmented Insulin Pump Therapy in Youth and Adults With Type 1 Diabetes With Sub-optimal Glucose Control Under Free Living Conditions
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 15
- 主要终点
- Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels
研究概览
简要总结
The main study objective is to determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy alone.
This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a three-month period of home study during which day and night glucose levels will be controlled either by a closed loop system combined with pump suspend feature (intervention group) or by sensor augmented insulin pump therapy (control group).
It is expected that up to 100 subjects, aiming for 84 randomised subjects [42 youth (6 to 21 years), and 42 adults (22 years and older)], with type 1 diabetes will be recruited through paediatric and adult outpatient diabetes clinics in each of the investigation centres. Subjects who drop out within the first four weeks of the intervention may be replaced. Participants will all be on subcutaneous insulin pump therapy and will have proven competencies both in the use of the study insulin pump and the study CGM device.
Subjects in the intervention group will receive appropriate training in the safe use of closed loop insulin delivery system and pump suspend feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in the time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels during the 12 week free living phase. Secondary outcomes are HbA1 at the end of treatment period, the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes.
详细描述
Purpose of the study:
To determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy.
Study objectives:
- EFFICACY: The objective is to assess efficacy of day and night automated closed loop glucose control combined with pump suspend feature in maintaining glucose levels within the target range from 3.9 to 10.0mmol/l (70 to 180mg/dl) based on subcutaneous continuous glucose monitoring (CGM), as compared to sensor augmented insulin pump therapy.
- SAFETY: The objective is to evaluate the safety of day and night automated closed loop glucose control combined with pump suspend feature, in terms of episodes of severe hypoglycaemia and other adverse events.
- UTILITY: The objective is to determine the frequency and duration of the use of the automated closed loop system.
- PSYCHOSOCIAL: Subjects' and family members' perception in terms of life-style change, diabetes management and fear of hypoglycaemia will be assessed using validated questionnaires and semi-structured qualitative interviews. Cognitive functions will be assessed using validated computerized cognitive tests.
Study design:
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
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject is at least 6 years or older [with equal proportion of youth (6 to 21 years) and adults (22 years and older)]
- •The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative
- •The subject will have been an insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator
- •The subject is treated with one of the rapid acting insulin analogues (insulin Aspart, Lispro or Glulisine)
- •The subject is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day
- •Screening HbA1c ≥ 7.5% (58.5mmol/mol) and ≤ 10 % (86mmol/mol) based on analysis from local laboratory or equivalent [with equal proportion of subjects above and below HbA1c 8.5% (69mmol/mol)]
- •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
- •The subject is willing to restrict alcohol consumption to ≤ 2 units per day throughout the study period
- •Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening.
- •The subject lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance.
- •The subject has access to WIFi at home.
排除标准
- •Non-type 1 diabetes mellitus including those secondary to chronic disease
- •Subject using real-time CGM on regular basis in preceding 3 months
- •Any other 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 or subject is being treated for hypothyroidism at time of screening
- •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
- •Subjects with clinically significant nephropathy (eGFR < 45ml/min) or on dialysis, neuropathy or active retinopathy (defined as presence of maculopathy or proliferative changes) as judged by the investigator
- •Adults: one or more episodes of severe hypoglycaemia as defined by American Diabetes Association (33) in preceding 6 months; Youth: recurrent incidents of severe hypoglycaemia during the previous 6 months (Adults and adolescents: severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions including episodes of hypoglycaemia severe enough to cause unconsciousness, seizures or attendance at hospital; children: severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness);
- •Random C-peptide > 100pmol/l with concomitant plasma glucose >4 mmol/l (72 mg/dl)
- •Regular use of acetaminophen
- •Lack of reliable telephone facility for contact
- •Total daily insulin dose ≥ 2 IU/kg/day
- •Total daily insulin dose < 15 IU/day
- •Pregnancy, planned pregnancy, or breast feeding
- •Severe visual impairment
- •Severe hearing impairment
- •Significantly reduced hypoglycaemia awareness in subjects 18 year and older (screening Gold score > 4)
- •Subjects using implanted internal pace-maker
- •Patients with 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 at places of the body, which potentially are possible to be used for localisation of the glucose sensor)
- •Subject is currently abusing illicit drugs
- •Subject is currently abusing prescription drugs
- •Subject is currently abusing alcohol
- •Subject is using pramlintide (Symlin) at time of screening
- •Subject has elective surgery planned that requires general anaesthesia during the course of the study
- •Subject is a shift worker with working hours between 10pm and 8am
- •Subject has a sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- •Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
- •Subject diagnosed with current eating disorder such as anorexia or bulimia
- •Subject plans to use significant quantity of herbal preparations (use of over the counter herbal preparation for 30 consecutive days or longer period during the study) or significant quantity of vitamin supplements (four times the recommended daily allowance used for 30 consecutive days or longer period during the study) during the course of their participation in the study
结局指标
主要结局
Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels
时间窗: 12 week intervention phase
both arms
次要结局
- AUC of glucose below 3.5mmol/l (63mg/dl)(12 week intervention phase)
- The time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)(12 week intervention phase)
- Change of body weight from screening to end of study(12 week intervention phase)
- The time with glucose levels < 3.5 mmol/l (63mg/dl) and <2.8 mmol/l (50mg/dl)(12 week intervention phase)
- HbA1c at the end of treatment period(HbA1c will be taken at the end of 12-week study intervention.)
- Time spent above target glucose (10.0 mmol/l) (180 mg/dl)(12 week intervention phase)
- Total, basal and bolus insulin dose(12 week intervention phase)
- Coefficient of variation of glucose levels(12 week intervention phase)
- Time spent below target glucose (3.9mmol/l)(70mg/dl)(12 week intervention phase)
- Average of glucose levels(12 week intervention phase)
- Standard deviation of glucose levels(12 week intervention phase)
- Number of pump suspend events(12 week intervention phase)
研究者
Dr Roman Hovorka
Director of Research
University of Cambridge