Clinical trial NCT06463483: Automated Insulin Delivery in Adults With Advanced Kidney Disease
Official title: Glucose Control With Medtronic 780G System in Adults With Diabetes and Advanced Renal Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chronic Kidney Diseases
Diabetes Mellitus
Keywords: Diabetes
Automated Insulin Delivery
Dialysis
Chronic Kidney Diseases
Insulin
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2024-06-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Diabetes is the leading cause of kidney failure in the UK. Many people with diabetes and advanced kidney failure inject themselves with insulin and do finger-prick blood glucose tests. Managing diabetes in people with advanced kidney disease is hard, with fluctuating glucose levels and an increased risk of unsafe low glucose levels.

There are currently continuous glucose monitors (CGM), which allow people to monitor glucose without painful fingerprick tests. CGM can be combined with insulin pumps to create automated insulin delivery systems (AID) that deliver insulin automatically to control glucose. AID systems are currently used in people with type 1 diabetes, but they are not used in people with type 2 diabetes. There is little information on how these systems might help people with diabetes and advanced kidney failure and on dialysis.

This study will investigate whether automated insulin delivery can improve glucose levels and quality of life in people with diabetes treated with more than one insulin injection with advanced kidney failure and/or undergoing regular dialysis treatment. This study will be a feasibility study conducted in a single centre (Imperial College, London) and be of a cross-over design. The study will aim to complete 12 people. Participants will wear a glucose sensor at the start. In random order, half will start AID followed by the usual treatment, while the other half will start the usual treatment followed by AID treatment. The duration of each treatment stage is eight weeks. The study will last about 22 weeks for each participant. Investigators will compare the glucose levels in the AID group with the usual care group to see if there is a difference. Questionnaires and interviews will help us understand participants' experiences. Investigators will carefully monitor the safety of participants.

Detailed description: This will be a single-centre, prospective, open-label, two-stage, randomized crossover study comparing automated subcutaneous insulin delivery (AID), also known as Hybrid Closed Loop (HCL) therapy using the 780G system with usual insulin therapy plus continuous glucose monitoring (CGM) in people with type 1 and type 2 diabetes complicated by advanced renal disease and managed with insulin. The study will be conducted at Imperial College Healthcare NHS Trust.

Duration of each treatment arm is 8 weeks

Eligibility criteria: Inclusion Criteria:

* 1. Age 18-70 years inclusive
* 2. Type 1 diabetes of at least 1-year duration or insulin-requiring type 2 diabetes managed with multiple daily injections (MDI \[ie separate rapid-acting and basal insulin injections\]) or insulin pump therapy (CSII)
* 3. The HbA1c \<10.5% (\<91 mmol/mol)
* 4. The total daily dose of insulin \<200Units
* 5. The participant is willing and able to implement the study requirements.
* 6. Participant has advanced renal disease (Group A: Stage 3b or greater renal failure (eGFR \<45millilitres/minute/1.73m2); Group B: ESKD requiring peritoneal dialysis; Group C: ESKD requiring haemodialysis
* 7. Participants (and carer where applicable) should be able to speak and understand English sufficiently for safe study conduct
* 8. The participant has internet or smartphone access, enabling upload of the 780G system data to cloud-based software

Exclusion Criteria:

* 1. The participant is already using an AID system
* 2. The participant is treated with sulphonylureas (SGLT2 inhibitors, metformin, and GLP1 analogues may be used within regulatory guidelines) in pre-dialysis participants (Group A). In Groups B \& C, noninsulin glucose-lowering therapies are not permitted, with the exception of GLP1 agonists used in preparation for transplantation
* 3. The participant has a recent history of diabetic ketoacidosis (\<6 months)
* 4. The use of systemic steroid therapy within the past four weeks (stable doses of steroids for \>8 weeks permitted)
* 5. The participant has significant cognitive impairment or major psychiatric history affecting safe study conduct
* 6. Known significant allergy to tape/ adhesives
* 7. Women who are pregnant or planning pregnancy
* 8. The participant has an active major life-threatening illness limiting the participants life expectancy to \<6 months
* 9. The participant is on hydroxyurea treatment or taking regular / daily paracetamol treatment (sensor interference)

Primary outcomes:
measure: Percent time in sensor glucose target range (3.9-10.0 mmol/L)
timeFrame: 3 weeks
Secondary outcomes:
measure: Percent time in sensor glucose target range (<3.0 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (<3.9 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (>10 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (<2.8 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (<3.3 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (>13.9 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (>16.7 mmol/L)
timeFrame: 3 weeks
measure: Percent time in sensor glucose target range (3.9-7.8 mmol/L)
timeFrame: 3 weeks
measure: Mean sensor glucose
timeFrame: 3 weeks
measure: Standard deviation and coefficient of variation of sensor glucose
timeFrame: 3 weeks
measure: The Diabetes Treatment Satisfaction Questionnaire status
timeFrame: 8 weeks
measure: Hypoglycaemia Fear Survey
timeFrame: 8 weeks
measure: EQ-5D-5L
timeFrame: 8 weeks
measure: Episodes of CGM time in <3.0mmol/L range lasting >15minutes
timeFrame: 3 weeks
measure: Number of hospital admissions with diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycaemia
timeFrame: 8 weeks
measure: Number of hospitalised and non-hospitalised patients with severe hypoglycaemia
timeFrame: 8 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: Boughton CK, Tripyla A, Hartnell S, Daly A, Herzig D, Wilinska ME, Czerlau C, Fry A, Bally L, Hovorka R. Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial. Nat Med. 2021 Aug;27(8):1471-1476. doi: 10.1038/s41591-021-01453-z. Epub 2021 Aug 4.
citation: Bally L, Gubler P, Thabit H, Hartnell S, Ruan Y, Wilinska ME, Evans ML, Semmo M, Vogt B, Coll AP, Stettler C, Hovorka R. Fully closed-loop insulin delivery improves glucose control of inpatients with type 2 diabetes receiving hemodialysis. Kidney Int. 2019 Sep;96(3):593-596. doi: 10.1016/j.kint.2019.03.006. Epub 2019 Mar 20.
citation: Lu JC, Lee P, Ierino F, MacIsaac RJ, Ekinci E, O'Neal D. Challenges of Glycemic Control in People With Diabetes and Advanced Kidney Disease and the Potential of Automated Insulin Delivery. J Diabetes Sci Technol. 2024 Nov;18(6):1500-1508. doi: 10.1177/19322968231174040. Epub 2023 May 10.