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

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.

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04025762

Acronym

DAN06

Enrollment

Registered

2019-07-19

Start date

2019-09-01

Completion date

2021-08-20

Last updated

2024-12-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arrythmia, Hypoglycemia, Type 1 Diabetes Mellitus

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.

Interventions

DEVICEHybrid closed-loop system (CamAPS FX)

Hybrid closed-loop system

DEVICESensor augmented pump therapy

Sensor augmented pump therapy

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

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.

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Proportion of Time Spent in the Target Sensor Glucose Range During the 16 Week Intervention Period (%)	16 weeks	Proportion of 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)

Secondary

Measure	Time frame
Average (mmol/L) of CGM Glucose Levels During the 16 Week Intervention Period	16 weeks
Total Daily Insulin Dose During the 16 Week Intervention Period (Units/Day)	16 weeks
Standard Deviation (mmol/L) of CGM Glucose Levels During the 16 Week Intervention Period	16 weeks
Proportion of Time With Glucose Levels < 3.0 mmol/l (54mg/dl) Based on CGM During the 16 Week Intervention Period (%)	16 weeks
HbA1c at the End of the 16 Week Intervention Period (mmol/Mol)	16 weeks
Proportion of Time Spent Below Target Glucose (3.9mmol/l) (70mg/dl) Based on CGM During the 16 Week Intervention Period (%)	16 weeks
Proportion of Time Spent Above Target Glucose (10.0 mmol/l) (180 mg/dl) Based on CGM During the 16 Week Intervention Period (%)	16 weeks
Proportion of Time With Glucose Levels < 3.5 mmol/l (63mg/dl) Based on CGM During the 16 Week Intervention Period (%)	16 weeks
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 (%)	16 weeks

Other

Measure	Time frame	Description
Sleep Quality Assessment	14 days	Sleep quality assessment using data collected by Actiwatch
Cardiac Arrythmia Analysis	5-7 days	Holter monitor data at the fourth month in the two treatment groups
The Proportion of Time of Use of the Closed-loop System at Home During the 16 Week Intervention Period (%)	16 weeks	Utility evaluation

Countries

United Kingdom

Participant flow

Pre-assignment details

One participant withdrew during the run-in period

Participants by arm

Arm	Count
Initial Use of Day and Night Hybrid Closed Loop Control Followed by Sensor Augmented Pump Therapy Run-in period (3-4 weeks) 16 weeks of day and night hybrid closed-loop system (CamAPS FX) consisting 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 Hybrid closed-loop system (CamAPS FX): Hybrid closed-loop system Washout period (4 weeks)	20
Initial Use of Sensor Augmented Pump Therapy Followed by Day and Night Hybrid Closed Loop Control Run-in period (3-4 weeks) 16 weeks of the comparator consisting of Dana RS insulin pump (Sooil) and G6 real-time CGM sensor (Dexcom) Sensor augmented pump therapy: Sensor augmented pump therapy Washout period (4 weeks) 16 weeks of day and night hybrid closed-loop system (CamAPS FX) consisting 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 Hybrid closed-loop system (CamAPS FX): Hybrid closed-loop system	17
Total	37

Withdrawals & dropouts

Period	Reason	FG000	FG001
Crossover Study Period 1 (16 Weeks)	Death	0	1

Baseline characteristics

Characteristic	Initial Use of Sensor Augmented Pump Therapy Followed by Day and Night Hybrid Closed Loop Control	Initial Use of Day and Night Hybrid Closed Loop Control Followed by Sensor Augmented Pump Therapy	Total
Age, Continuous	67 years	68 years	68 years
Charlson comorbidity index (lower value indicates less comorbidity burden)	4 points on a scale (minimum 0 maximum 37) STANDARD_DEVIATION 1	4 points on a scale (minimum 0 maximum 37) STANDARD_DEVIATION 2	4 points on a scale (minimum 0 maximum 37) STANDARD_DEVIATION 1
Continuous glucose monitor user	12 participants	13 participants	25 participants
Duration of diabetes	38 years	38 years	38 years
Duration of pump therapy	9 years	11 years	10 years
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants	20 Participants	37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
HbA1c, %	7.4 % of glycated hemoglobin STANDARD_DEVIATION 0.9	7.5 % of glycated hemoglobin STANDARD_DEVIATION 1	7.4 % of glycated hemoglobin STANDARD_DEVIATION 0.9
HbA1c, mmol/mol	57 mmol/mol STANDARD_DEVIATION 9	58 mmol/mol STANDARD_DEVIATION 10	57 mmol/mol STANDARD_DEVIATION 10
Region of Enrollment Austria	2 Participants	4 Participants	6 Participants
Region of Enrollment United Kingdom	15 Participants	16 Participants	31 Participants
Sex: Female, Male Female	8 Participants	8 Participants	16 Participants
Sex: Female, Male Male	9 Participants	12 Participants	21 Participants
Total daily insulin, units per day	40.0 units/day	45.8 units/day	45.1 units/day

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 36	1 / 37	0 / 37	0 / 36
other Total, other adverse events	4 / 36	7 / 37	2 / 37	1 / 36
serious Total, serious adverse events	0 / 36	1 / 37	1 / 37	0 / 36

Outcome results

Primary

Proportion of Time Spent in the Target Sensor Glucose Range During the 16 Week Intervention Period (%)

Proportion of 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)

Time frame: 16 weeks