Chronic Kidney Disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Dialysis, Hemodialysis, Peritoneal Dialysis
Conditions
Keywords
Insulin Infusion Systems, Continuous Glucose Monitoring, Randomized Controlled Trial, Equipment Safety, Glycemic Control, Time-in-range
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.
Interventions
DEVICE2nd Generation Automated Insulin Delivery (AID) system
The AID system will initially commence delivery by insulin pump post-randomisation without the AID in operation and with predictive low glucose suspend activated for a period of two weeks. Once safety has been established, the autocorrect function can be activated and the setpoint reduced to 5.5 mmol/L. Throughout the study insulin pump uploads will be reviewed twice weekly initially and at least weekly thereafter.
Sponsors
Steno Diabetes Center Copenhagen
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent time in sensor glucose target range (3.9-10.0 mmol/L) | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Quality | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: Pittsburgh Sleep Quality Index \[PSQI\] |
| Cognitive function | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: Montreal Cognitive Assessment (MOCA) |
| Sarcopenia | End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | SARC-F questionnaire |
| Hypoglycaemia awareness | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: Gold Score and Clarke Score |
| Proportion of time spent <2.8 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent <3.0 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent <3.3 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent <3.9 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent 3.9-7.8 | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent >10.0 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent >13.9 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Proportion of time spent >16.7 mmol/L | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Glucose variability (SD and coefficient of variation) | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Mean glucose | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| HbA1c | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Blood sample |
| Episodes of CGM time in < 3.0 mmol/L range lasting >15 minutes | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Assessed by 3 continuous weeks of CGM |
| Diabetic ketoacidosis og Hyperosmolar non-ketotic hyperglycemia | Week 0-22 | Hospital presentations with either of the above |
| eGFR (estimated glomerular filtration rate) | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Based on serum creatinine measurements, using the CKD-EPI equation. Only measured in patients from the CKD-group |
| Potassium pre-dialysis | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Blood sample. Only measured in patients from the HD-group |
| Urine albumine-to-creatinine ratio | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Urine sample. Only measured in patients from the CKD-group |
| Actigraph Metrics for sleep architecture | End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22 | Used concurrently with the CGM |
| Sleep diary | Week 6-22 | — |
| Proportion of time Automode is active | Weekly assessed: week 6-22 | Registered through uploads from insulin pump in the intervention arm |
| Diabetic ketoacidosis | Week 0-22 | — |
| Severe hypoglycemia | Week 0-22 | Requiring third party assistance |
| Serious Adverse Event | Week 0-22 | — |
| Unanticipated Serious Adverse Device Event | Week 0-22 | — |
| Satisfaction with diabetes treatment | Enrollment visit: week 0; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: The Diabetes Treatment Satisfaction Questionnaire status \[DTSQs\] |
| Fear of hypoglycaemia | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: Hypoglycaemia Fear Survey \[HFS-II\] |
| Semi-structured interview | End of phase 1: week 14; end of phase 2: week 22 | Influence of kidney disease on diabetes management and experience with the AID. Only performed in intervention arm. |
| Health-related quality of life | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: EQ-5D |
| Diabetes distress | Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: Problem Areas in Diabetes \[PAID\] |
| Frailty | End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22 | Questionnaire: Fried Frailty |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORTobias Bomholt, MD, PhD
Department of Nephrology, Rigshospitalet, University of Copenhagen
Outcome results
None listed