24/7 Closed-loop in Older Subjects With Type 1 Diabetes

Study Overview
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Brief Summary
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The main objective of this open-label, multi-centre, randomised, crossover design study is to determine whether automated day and night closed-loop insulin delivery for 16 weeks under free living conditions is safer and more efficacious compared to sensor augmented insulin pump therapy in older adults with type 1 diabetes. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L (70 and 180 mg/dl) as recorded by CGM. Secondary outcomes are the HbA1c, time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Measures of human factor assessments, cardiac arrhythmias and objective sleep quality assessment will also be evaluated in this study.

Detailed Description
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No study thus far has specifically evaluated use of closed-loop insulin delivery in older adults with type 1 diabetes. During our previous closed-loop studies, if there is a communication failure between the algorithm device and the insulin pump, the pump is set to deliver pre-programmed basal insulin rates after about 30 to 60 minutes.The main objective of this study is to determine whether automated day and night closed-loop insulin delivery for 16 weeks under free living conditions is safer and more efficacious compared to sensor augmented insulin pump therapy in older adults with type 1 diabetes. This is an open-label, multi-centre, randomised, crossover design study, involving a 4-6 week run-in period, followed by two 4 months study periods during which glucose levels will be controlled either by an automated closed-loop system or by sensor-augmented pump therapy in random order. A total of up to 42 adults (aiming for 36 completed subjects) aged 60 years and older with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods in participating centres. Subjects who drop out of the study within the first 6 weeks of the first intervention period will be replaced. Subjects will receive appropriate training in the safe use of closed-loop insulin delivery system. Subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L (70 and 180mg/dl) as recorded by CGM. Secondary outcomes are the HbA1c, time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Measures of human factor assessments, cardiac arrhythmia and objective sleep quality assessment will also be evaluated in this study.

Official Title
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An Open-label, Multi-centre, Randomised, Two-period, Crossover Study to Assess the Efficacy, Safety and Utility of 16 Week Day and Night Automated Closed-loop Glucose Control Under Free Living Conditions Compared to Sensor Augmented Insulin Pump Therapy in Older Adults With Type 1 Diabetes.

Conditions
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Type 1 Diabetes Mellitus, Hypoglycemia, Arrythmia

Intervention / Treatment
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* Device: Hybrid closed-loop system (CamAPS FX)
* Device: Sensor augmented pump therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60 years and above Type 1 diabetes as defined by WHO for at least 1 year or confirmed C-peptide negative On insulin pump for at least 3 months with good knowledge of insulin self-adjustment Treated with one of the U-100 rapid acting insulin analogues only (insulin Aspart, Lispro, Faster insulin Aspart but not Glulisine) Willing to perform regular capillary blood glucose monitoring HbA1c ≤ 10% (86 mmol/mmol) based on analysis from central laboratory or equivalent Literate in English Having a care partner who is aware of the subject's location and is trained to administer intramuscular glucagon and able to seek emergency assistance Willing to wear closed-loop system at home and at work place Willing to follow study specific instructions Willing to upload pump and CGM data at regular intervals Has access to WiFi Exclusion Criteria: Non-type 1 diabetes mellitus Use of a closed-loop system within the last 30 days Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results Use of any glucose-lowering agent (such as Pramlintide, Metformin, GLP-1 analogs) in the 3 months prior to enrolment or any use of SGLT2 inhibitors Untreated coeliac disease, adrenal insufficiency or hypothyroidism Known or suspected allergy against insulin More than one episodes of severe hypoglycaemia as defined by American Diabetes Association in preceding 6 months Random C-peptide > 200pmol/l with concomitant plasma glucose >4 mmol/l (72 mg/dl) Lack of reliable telephone facility for contact Total daily insulin dose >/= 2 IU/kg/day Total daily insulin dose < 15 IU/day 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 could potentially 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 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) known to affect glucose metabolism and/or blood glucose levels during the course of their participation in the study Subject not proficient in English (UK), or German (Austria) Additional exclusion criteria specific for Austria Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates). Positive alcohol breath test. Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus (HIV) 1 antibodies, anti-HIV2 antibodies.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: An open-label, multi-centre randomised, two-period crossover study comparing day and night automated closed-loop glucose control with sensor-augmented pump therapy.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Day and night hybrid closed loop control<br>The day and night hybrid closed-loop system (CamAPS FX) will consist of: Dana RS insulin pump (Sooil) G6 real-time CGM sensor (Dexcom) An unlocked android smartphone hosting the CamAPS FX app with Cambridge control algorithm | Device: Hybrid closed-loop system (CamAPS FX)<br>* Hybrid closed-loop system<br>|
| Active Comparator: Sensor augmented pump therapy<br>The comparator will consist of Dana RS insulin pump (Sooil) and G6 real-time CGM sensor (Dexcom) | Device: Sensor augmented pump therapy<br>* Sensor augmented pump therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent in the target sensor glucose range | Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on continuous glucose monitoring (CGM) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c at the end of treatment period |  | 16 weeks | 
| Time spent below target glucose (3.9mmol/l) (70mg/dl) based on CGM |  | 16 weeks | 
| Time spent above target glucose (10.0 mmol/l) (180 mg/dl) based on CGM |  | 16 weeks | 
| Average, standard deviation, and coefficient of variation of CGM glucose levels |  | 16 weeks | 
| Time with glucose levels < 3.5 mmol/l (63mg/dl) and < 3.0 mmol/l (54mg/dl) based on CGM |  | 16 weeks | 
| Time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl) |  | 16 weeks | 
| Total, basal and bolus insulin dose |  | 16 weeks |