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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Hemodialysis; Peritoneal Dialysis; Chronic Kidney Disease; Dialysis
• Intervention / Treatment: Device: 2nd Generation Automated Insulin Delivery (AID) system

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kirsten Nørgaard, MD, DMSc; Phone Number: +45 27131011; Email: Kirsten.Noergaard@regionh.dk
• Study Contact Backup: Name: Christine L. Meyer-Olesen, MD; Phone Number: +45 35450630; Email: Christine.Olesen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Tobias Bomholt
    • Contact: Tobias Bomholt, MD, PhD; Phone Number: +4535457952; Email: Tobias.bomholt@regionh.dk
    • Contact: Christine Meyer Olesen, MD; Phone Number: 21495144; Email: clmolesen@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention Group; 2nd Generation Automated Insulin Delivery system (Medtronic MiniMed 780G)	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.; Other Names: Medtronic MiniMed 780G
No Intervention: Control Group; Usual care consisting of participants current insulin-treatment (either multiple daily injection with insulin or traditional insulin pump therapy with manual determination of insulin dosing) and real-time CGM if already used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
Diabetic ketoacidosis og Hyperosmolar non-ketotic hyperglycemia	Hospital presentations with either of the above	Week 0-22
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
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
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
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
Sleep diary		Week 6-22
Proportion of time Automode is active	Registered through uploads from insulin pump in the intervention arm	Weekly assessed: week 6-22
Diabetic ketoacidosis		Week 0-22
Severe hypoglycemia	Requiring third party assistance	Week 0-22
Serious Adverse Event		Week 0-22
Unanticipated Serious Adverse Device Event		Week 0-22
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
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
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
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
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
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
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
Sarcopenia	SARC-F questionnaire	End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22
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
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
Frailty	Questionnaire: Fried Frailty	End of run in phase: week 6; end of phase 1: week 14; end of phase 2: week 22

Collaborators and Investigators

• Sponsor: Steno Diabetes Center Copenhagen
• Collaborators: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Tobias Bomholt, MD, PhD, Department of Nephrology, Rigshospitalet, University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Continuous Glucose Monitoring; Randomized Controlled Trial; Glycemic Control; Time-in-range; Insulin Infusion Systems; Equipment Safety
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: AID-study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No