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

Type 1 Diabetes Mellitus Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04025762
• Other study ID #: DAN06
• Status: Completed
• Phase: N/A
• Start date: September 1, 2019
• Est. completion date: August 20, 2021

Study information

• Verified date: September 2021
• Source: University of Cambridge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: August 20, 2021
• Est. primary completion date: August 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arrythmia
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes Mellitus

Intervention

Device:
• Hybrid closed-loop system (CamAPS FX)
Hybrid closed-loop system
• Sensor augmented pump therapy
Sensor augmented pump therapy

Locations

Country	Name	City	State
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Manchester Royal Infirmary	Manchester

Sponsors (4)

Lead Sponsor	Collaborator
University of Cambridge	Manchester University NHS Foundation Trust, Medical University of Graz, University Hospital Birmingham NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Utility evaluation	The frequency and duration of use of the closed-loop system at home.	16 weeks
Other	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
Other	Cardiac arrythmia analysis	Holter monitor data at the fourth month in the two treatment groups	5-7 days
Other	Sleep quality assessment	Sleep quality assessment using data collected by Actiwatch	14 days
Primary	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	HbA1c at the end of treatment period		16 weeks
Secondary	Time spent below target glucose (3.9mmol/l) (70mg/dl) based on CGM		16 weeks
Secondary	Time spent above target glucose (10.0 mmol/l) (180 mg/dl) based on CGM		16 weeks
Secondary	Average, standard deviation, and coefficient of variation of CGM glucose levels		16 weeks
Secondary	Time with glucose levels < 3.5 mmol/l (63mg/dl) and < 3.0 mmol/l (54mg/dl) based on CGM		16 weeks
Secondary	Time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)		16 weeks
Secondary	Total, basal and bolus insulin dose		16 weeks