24/7 Closed-loop in Older Subjects With Type 1 Diabetes (DAN06)

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Type 1 Diabetes Mellitus; Arrythmia
• Intervention / Treatment: Device: Hybrid closed-loop system (CamAPS FX); Device: Sensor augmented pump therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Manchester, United Kingdom
    • Manchester Royal Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Day and night hybrid closed loop control; 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); Hybrid closed-loop system
Active Comparator: Sensor augmented pump therapy; The comparator will consist of Dana RS insulin pump (Sooil) and G6 real-time CGM sensor (Dexcom)	Device: Sensor augmented pump therapy; Sensor augmented pump therapy

What is the study measuring?

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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Utility evaluation	The frequency and duration of use of the closed-loop system at home.	16 weeks
Human Factor assessment	Cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial will be assessed using validated surveys and focus groups	30 minutes
Cardiac arrythmia analysis	Holter monitor data at the fourth month in the two treatment groups	5-7 days
Sleep quality assessment	Sleep quality assessment using data collected by Actiwatch	14 days

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Medical University of Graz; University Hospital Birmingham NHS Foundation Trust; Manchester University NHS Foundation Trust
• Investigators: Principal Investigator: Roman Hovorka, PhD, University of Cambridge

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): August 20, 2021
• Study Completion (Actual): August 20, 2021

Study Registration Dates

• First Submitted: July 16, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 4, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: DAN06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication. To gain access, data requestors will need to sign a data access agreement.

Fully anonymised data may be shared with third parties (EU or non-EU based) for the purposes of advancing management and treatment of diabetes.

• IPD Sharing Time Frame: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Access Criteria: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No