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

Primary Purpose

Type 1 Diabetes Mellitus, Hypoglycemia, Arrythmia

Status

Completed

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Hybrid closed-loop system (CamAPS FX)

Sensor augmented pump therapy

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Cambridge University Hospitals NHS Foundation Trust
Manchester Royal Infirmary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Day and night hybrid closed loop control

Sensor augmented pump therapy

Arm Description

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

The comparator will consist of Dana RS insulin pump (Sooil) and G6 real-time CGM sensor (Dexcom)

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

HbA1c at the end of treatment period

Time spent below target glucose (3.9mmol/l) (70mg/dl) based on CGM

Time spent above target glucose (10.0 mmol/l) (180 mg/dl) based on CGM

Average, standard deviation, and coefficient of variation of CGM glucose levels

Time with glucose levels < 3.5 mmol/l (63mg/dl) and < 3.0 mmol/l (54mg/dl) based on CGM

Time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)

Total, basal and bolus insulin dose

Full Information

NCT ID

NCT04025762

First Posted

July 16, 2019

Last Updated

September 4, 2021

Sponsor

University of Cambridge

Collaborators

Manchester University NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Medical University of Graz

1. Study Identification

Unique Protocol Identification Number

NCT04025762

Brief Title

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

Acronym

DAN06

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

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

September 1, 2019 (Actual)

Primary Completion Date

August 20, 2021 (Actual)

Study Completion Date

August 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Cambridge

Collaborators

Manchester University NHS Foundation Trust, University Hospital Birmingham NHS Foundation Trust, Medical University of Graz

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus, Hypoglycemia, Arrythmia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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)

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Day and night hybrid closed loop control

Arm Type

Experimental

Arm Description

Arm Title

Sensor augmented pump therapy

Arm Type

Active Comparator

Arm Description

The comparator will consist of Dana RS insulin pump (Sooil) and G6 real-time CGM sensor (Dexcom)

Intervention Type

Device

Intervention Name(s)

Hybrid closed-loop system (CamAPS FX)

Intervention Description

Hybrid closed-loop system

Intervention Type

Device

Intervention Name(s)

Sensor augmented pump therapy

Intervention Description

Sensor augmented pump therapy

Primary Outcome Measure Information:

Title

Time spent in the target sensor glucose range

Description

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

Secondary Outcome Measure Information:

Title

HbA1c at the end of treatment period

Time Frame

16 weeks

Title

Time spent below target glucose (3.9mmol/l) (70mg/dl) based on CGM

Time Frame

16 weeks

Title

Time spent above target glucose (10.0 mmol/l) (180 mg/dl) based on CGM

Time Frame

16 weeks

Title

Average, standard deviation, and coefficient of variation of CGM glucose levels

Time Frame

16 weeks

Title

Time with glucose levels < 3.5 mmol/l (63mg/dl) and < 3.0 mmol/l (54mg/dl) based on CGM

Time Frame

16 weeks

Title

Time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)

Time Frame

16 weeks

Title

Total, basal and bolus insulin dose

Time Frame

16 weeks

Other Pre-specified Outcome Measures:

Title

Utility evaluation

Description

The frequency and duration of use of the closed-loop system at home.

Time Frame

16 weeks

Title

Human Factor assessment

Description

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

Time Frame

30 minutes

Title

Cardiac arrythmia analysis

Description

Holter monitor data at the fourth month in the two treatment groups

Time Frame

5-7 days

Title

Sleep quality assessment

Description

Sleep quality assessment using data collected by Actiwatch

Time Frame

14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roman Hovorka, PhD

Organizational Affiliation

University of Cambridge

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cambridge University Hospitals NHS Foundation Trust

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Facility Name

Manchester Royal Infirmary

City

Manchester

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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

IPD Sharing Access Criteria

Citations:

PubMed Identifier

35359882

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.

Results Reference

derived

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

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