Clinical trial NCT04025762: 24/7 Closed-loop in Older Subjects With Type 1 Diabetes
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Hypoglycemia
Arrythmia
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Manchester University NHS Foundation Trust
name: University Hospital Birmingham NHS Foundation Trust
name: Medical University of Graz
First posted: 2019-07-19
Enrollment: 38
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 60 years and above
2. Type 1 diabetes as defined by WHO for at least 1 year or confirmed C-peptide negative
3. On insulin pump for at least 3 months with good knowledge of insulin self-adjustment
4. Treated with one of the U-100 rapid acting insulin analogues only (insulin Aspart, Lispro, Faster insulin Aspart but not Glulisine)
5. Willing to perform regular capillary blood glucose monitoring
6. HbA1c ≤ 10% (86 mmol/mmol) based on analysis from central laboratory or equivalent
7. Literate in English
8. 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
9. Willing to wear closed-loop system at home and at work place
10. Willing to follow study specific instructions
11. Willing to upload pump and CGM data at regular intervals
12. Has access to WiFi

Exclusion Criteria:

1. Non-type 1 diabetes mellitus
2. Use of a closed-loop system within the last 30 days
3. Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
4. 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
5. Untreated coeliac disease, adrenal insufficiency or hypothyroidism
6. Known or suspected allergy against insulin
7. More than one episodes of severe hypoglycaemia as defined by American Diabetes Association in preceding 6 months
8. Random C-peptide \> 200pmol/l with concomitant plasma glucose \>4 mmol/l (72 mg/dl)
9. Lack of reliable telephone facility for contact
10. Total daily insulin dose \>/= 2 IU/kg/day
11. Total daily insulin dose \< 15 IU/day
12. Severe visual impairment
13. Severe hearing impairment
14. Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
15. 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)
16. Subject is currently abusing illicit drugs
17. Subject is currently abusing prescription drugs
18. Subject is currently abusing alcohol
19. Subject has elective surgery planned that requires general anaesthesia during the course of the study
20. Subject is a shift worker with working hours between 10pm and 8am
21. Subject has a sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
22. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
23. Subject diagnosed with current eating disorder such as anorexia or bulimia
24. 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
25. Subject not proficient in English (UK), or German (Austria)

Additional exclusion criteria specific for Austria

1. Positive results on urine drug screen (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
2. Positive alcohol breath test.
3. 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.

Primary outcomes:
measure: Proportion of Time Spent in the Target Sensor Glucose Range During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
Secondary outcomes:
measure: HbA1c at the End of the 16 Week Intervention Period (mmol/Mol)
timeFrame: 16 weeks
measure: Proportion of Time Spent Below Target Glucose (3.9mmol/l) (70mg/dl) Based on CGM During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
measure: Proportion of Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl) Based on CGM During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
measure: Average (mmol/L) of CGM Glucose Levels During the 16 Week Intervention Period
timeFrame: 16 weeks
measure: Proportion of Time With Glucose Levels < 3.5 mmol/l (63mg/dl) Based on CGM During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
measure: Proportion of Time With Glucose Levels in the Significant Hyperglycaemia (Glucose Levels > 16.7 mmol/l) (300mg/dl) Based on CGM During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
measure: Total Daily Insulin Dose During the 16 Week Intervention Period (Units/Day)
timeFrame: 16 weeks
measure: Standard Deviation (mmol/L) of CGM Glucose Levels During the 16 Week Intervention Period
timeFrame: 16 weeks
measure: Proportion of Time With Glucose Levels < 3.0 mmol/l (54mg/dl) Based on CGM During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
Other outcomes:
measure: The Proportion of Time of Use of the Closed-loop System at Home During the 16 Week Intervention Period (%)
timeFrame: 16 weeks
measure: Cardiac Arrythmia Analysis
timeFrame: 5-7 days
measure: Sleep Quality Assessment
timeFrame: 14 days
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: University of Cambridge
name: Roman Hovorka, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boughton CK, Hartnell S, Thabit H, Mubita WM, Draxlbauer K, Poettler T, Wilinska ME, Hood KK, Mader JK, Narendran P, Leelarathna L, Evans ML, Hovorka R. Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study. Lancet Healthy Longev. 2022 Mar;3(3):e135-e142. doi: 10.1016/S2666-7568(22)00005-8. Epub 2022 Mar 7.