Clinical trial NCT06330194: Next Generation Advanced Insulin Delivery System in Adults With Diabetes and Advanced Renal Disease
Official title: Glucose Control With a Next Generation Advanced Insulin Delivery System in Adults With Diabetes and Advanced Renal Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Dialysis
Chronic Kidney Disease
Diabetes Mellitus, Type 2
Diabetes Mellitus, Type 1
Hemodialysis
Peritoneal Dialysis
Keywords: Insulin Infusion Systems
Continuous Glucose Monitoring
Randomized Controlled Trial
Equipment Safety
Glycemic Control
Time-in-range
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
First posted: 2024-03-26
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Design: Prospective, open-label, two-stage randomised-crossover study.

Population: Patients with type 1 or type 2 diabetes undergoing hemodialysis (n=5), peritoneal dialysis (n=5) or chronic kidney disease stage 3b to stage 5 (n=5).

Methods: Participants entering the study will have a four-to-six-week run-in phase with diabetes education. During the run-in phase three weeks of unblinded continous glucose monitoring (CGM) will be performed to assess baseline glucose levels.

All participants will be randomized to receive either eight weeks with an advanced insulin delivery (AID) System or eight weeks of control (usual care) with cross over at the end of the first eight weeks.

CGM study outcome data will be collected by identical methods, using unblinded-CGM devices, for participants in both intervention and control study arms.
Primary purpose: TREATMENT

Brief summary: The goal of this this randomized, clinical trial is to test an automated insulin delivery system (AID) in people with type 1 or type 2 diabetes who are on hemodialysis, peritoneal dialysis, or have advanced chronic kidney disease (CKD).

The main objective is:

• To test if the AID is superior in regulating blood sugar levels compared with usual care in patients with advanced renal disease

Secondary objectives are:

• To evaluate the impact on life quality, incidence of low blood sugar, and if the treatment is feasible in this population

Participants will be randomized to receive either eight weeks with the AID System (780G from Medtronic) or eight weeks of Control (usual care) with cross over at the end of the first eight weeks.

Researchers will compare blood sugar levels between the AID group and the Control group to determine if the AID system is superior in regulating blood sugar levels.

Detailed description: Dialysis patients with diabetes have a very short life expectancy likely caused by a high incidence of co-morbidities combined with an increased risk of hypoglycaemia and poor glycaemic control. In the past decades various diabetes technologies have revolutionised treatment, primarily in type 1 diabetes, but have also shown effect in type 2 diabetes. The Automated Insulin Delivery (AID) system combines continuous glucose monitoring (CGM) with an insulin pump that automatically infuse short-acting insulin subcutaneously and has shown remarkable results in improving glucose levels. We hypothesise that the AID system can lead to a substantial improvement in glycaemic control for patients receiving haemodialysis (HD), peritoneal dialysis (PD) and patients with chronic kidney disease (CKD) stage 3b to 5 (not on dialysis).

The primary objective is to determine if the AID system is superior in regulating glucose levels, in people living with type 1 and type 2 diabetes, receiving HD, PD or having advanced CKD, compared with usual care. Secondary objectives are to evaluate the impact on life quality, incidence of hypoglycaemia and if this treatment is feasible for this population

This prospective, open-label, two-stage randomized-crossover study is conducted at the Department of Nephrology, Rigshospitalet Copenhagen and Steno Diabetes Center Copenhagen. The study is performed in collaboration with six Australian centres (St Vincent's Melbourne, Royal Melbourne, Austin, Cairns Base, Flinders, and Canberra Hospitals).

A total of 15 participants will be recruited in Copenhagen, with participants evenly distributed across the three disease categories (HD, PD, and advanced CKD). Data collected from Copenhagen will be pooled with data obtained from the Australian centers.

Participants entering the study will have a four-to-six-week run-in phase with diabetes education (carbohydrate counting, inserting of CGM etc). Training will consist of three sessions of 2-4 hours with a dedicated diabetes nurse. During the run-in phase three weeks of unblinded CGM will be performed to assess baseline glucose levels. All participants will be randomized 1:1 to receive either eight weeks with the AID System (780G from Medtronic) or eight weeks of control (usual care) with cross over at the end of the first eight weeks.

The trial will be conducted in compliance with the Good Clinical Practice (GCP) guidelines, and written informed consent will be obtained before any trial activities are performed. The project including a plan for the handling of personal information will be approved by the Danish Data Protection Agency before initiation. If necessary, the Danish Medicines Agency and the responsible GCP unit will be granted access to journals, documents, and other materials relevant to the project. All participants will be assigned with a subject number and will be recorded on data sheets. Only tubes will appear with subject number and trial ID. Information on full name and social security and subject numbers will be stored separately.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained before any trial-related procedures are performed
2. Type 1 diabetes of at least 1-year duration or insulin requiring type 2 diabetes (Total insulin dose should be below 200 IE per day)
3. Maintenance HD, PD, or CKD stage 3b-5 (not on dialysis).
4. Subject must be willing and able to comply with trial protocol
5. HbA1c \<91 mmol/mol (10.5%)

All participants will require to have internet or mobile phone access enabling upload of the AID system data to cloud based software.

Exclusion Criteria:

1. History of ketoacidosis within the past 6 months
2. Moderate to severe cognitive impairment
3. Major allergy to tape/ adhesives
4. Women who are pregnant or planning pregnancy
5. Life-expectancy to \<6 months
6. Major psychiatric history
7. Treatment with sulphonylureas in pre-dialysis participants (SGLT2 inhibitors, metformin, and GLP1 analogues may be used within regulatory guidelines)
8. Treatment with non-insulin glucose lowering therapies may not be used on dialysis participants (with the exception of GLP1 agonists used in preparation for transplantation)
9. Systemic steroid treatment within 4 weeks (stable doses of steroids \>8 weeks allowed)
10. Visual impairment

Primary outcomes:
measure: Percent time in sensor glucose target range (3.9-10.0 mmol/L)
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary outcomes:
measure: Proportion of time spent <2.8 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent <3.0 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent <3.3 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent <3.9 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent 3.9-7.8
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent >10.0 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent >13.9 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Proportion of time spent >16.7 mmol/L
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Glucose variability (SD and coefficient of variation)
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Mean glucose
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: HbA1c
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Episodes of CGM time in < 3.0 mmol/L range lasting >15 minutes
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Diabetic ketoacidosis og Hyperosmolar non-ketotic hyperglycemia
timeFrame: Week 0-22
measure: eGFR (estimated glomerular filtration rate)
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Potassium pre-dialysis
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Urine albumine-to-creatinine ratio
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Actigraph Metrics for sleep architecture
timeFrame: End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
measure: Sleep diary
timeFrame: Week 6-22
measure: Proportion of time Automode is active
timeFrame: Weekly assessed: week 6-22
measure: Diabetic ketoacidosis
timeFrame: Week 0-22
measure: Severe hypoglycemia
timeFrame: Week 0-22
measure: Serious Adverse Event
timeFrame: Week 0-22
measure: Unanticipated Serious Adverse Device Event
timeFrame: Week 0-22
measure: Satisfaction with diabetes treatment
timeFrame: Enrollment visit: week 0; end of phase 1: week 14; end of phase 2: week 22
measure: Satisfaction with diabetes treatment
timeFrame: End of phase 1: week 14; end of phase 2: week 22
measure: Fear of hypoglycaemia
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Hypoglycaemia awareness
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Diabetes distress
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Sleep Quality
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Cognitive function
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Sarcopenia
timeFrame: End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Semi-structured interview
timeFrame: End of phase 1: week 14; end of phase 2: week 22
measure: Health-related quality of life
timeFrame: Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
measure: Frailty
timeFrame: End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Tobias Bomholt
Study officials:
affiliation: Department of Nephrology, Rigshospitalet, University of Copenhagen
name: Tobias Bomholt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: