Next Generation Advanced Insulin Delivery System in Adults With Diabetes and Advanced Renal Disease

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Glucose Control With a Next Generation Advanced Insulin Delivery System in Adults With Diabetes and Advanced Renal Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06330194
• Other study ID #: AID-study
• Status: Recruiting
• Phase: N/A
• Start date: April 18, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Steno Diabetes Center Copenhagen
• Contact: Kirsten Nørgaard, MD, DMSc
• Phone: +45 27131011
• Email: Kirsten.Noergaard[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Dialysis
• Hemodialysis
• Kidney Diseases
• Peritoneal Dialysis
• Renal Insufficiency, Chronic

Intervention

Device:
• 2nd 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.

Locations

Country	Name	City	State
Denmark	Tobias Bomholt	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Steno Diabetes Center Copenhagen	Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent time in sensor glucose target range (3.9-10.0 mmol/L)	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent <2.8 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent <3.0 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent <3.3 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent <3.9 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent 3.9-7.8	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent >10.0 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent >13.9 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Proportion of time spent >16.7 mmol/L	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Glucose variability (SD and coefficient of variation)	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Mean glucose	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	HbA1c	Blood sample	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Episodes of CGM time in < 3.0 mmol/L range lasting >15 minutes	Assessed by 3 continuous weeks of CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Diabetic ketoacidosis og Hyperosmolar non-ketotic hyperglycemia	Hospital presentations with either of the above	Week 0-22
Secondary	eGFR (estimated glomerular filtration rate)	Based on serum creatinine measurements, using the CKD-EPI equation. Only measured in patients from the CKD-group	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Potassium pre-dialysis	Blood sample. Only measured in patients from the HD-group	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Urine albumine-to-creatinine ratio	Urine sample. Only measured in patients from the CKD-group	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Actigraph Metrics for sleep architecture	Used concurrently with the CGM	End of run in phase: week 3-5; end of phase 1: week 11-13; end of phase 2: week 20-22
Secondary	Sleep diary		Week 6-22
Secondary	Proportion of time Automode is active	Registered through uploads from insulin pump in the intervention arm	Weekly assessed: week 6-22
Secondary	Diabetic ketoacidosis		Week 0-22
Secondary	Severe hypoglycemia	Requiring third party assistance	Week 0-22
Secondary	Serious Adverse Event		Week 0-22
Secondary	Unanticipated Serious Adverse Device Event		Week 0-22
Secondary	Satisfaction with diabetes treatment	Questionnaire: The Diabetes Treatment Satisfaction Questionnaire status [DTSQs]	Enrollment visit: week 0; end of phase 1: week 14; end of phase 2: week 22
Secondary	Satisfaction with diabetes treatment	Questionnaire: The Diabetes Treatment Satisfaction Questionnaire control version [DTSQc]	End of phase 1: week 14; end of phase 2: week 22
Secondary	Fear of hypoglycaemia	Questionnaire: Hypoglycaemia Fear Survey [HFS-II]	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Hypoglycaemia awareness	Questionnaire: Gold Score and Clarke Score	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Diabetes distress	Questionnaire: Problem Areas in Diabetes [PAID]	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Sleep Quality	Questionnaire: Pittsburgh Sleep Quality Index [PSQI]	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Cognitive function	Questionnaire: Montreal Cognitive Assessment (MOCA)	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Sarcopenia	SARC-F questionnaire	End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Semi-structured interview	Influence of kidney disease on diabetes management and experience with the AID. Only performed in intervention arm.	End of phase 1: week 14; end of phase 2: week 22
Secondary	Health-related quality of life	Questionnaire: EQ-5D	Enrollment visit: week 0; end of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
Secondary	Frailty	Questionnaire: Fried Frailty	End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22