Closed-loop in Adults With T2D Not Requiring Dialysis (AP-Renal)

An Open-label, Single-centre, Randomised, 2-period Cross-over Study to Assess the Efficacy, Safety and Utility of Fully Closed-loop Insulin Delivery in Comparison With Standard Care in Adults With Type 2 Diabetes Not Requiring Dialysis

The main objective of this study is to determine the efficacy, safety and utility of fully automated closed-loop glucose control in the home setting over an 8 week period in adults with type 2 diabetes (T2D). This study builds on previous and on-going studies of closed-loop systems that have been performed in Cambridge in adults with type 1 diabetes in the home setting, and in adults with type 2 diabetes in the inpatient setting.

This is an open-label, single centre, randomised, cross-over study, involving two home study periods during which glucose levels will be controlled either by a fully automated closed-loop system or by participants' usual insulin therapy in random order. Each treatment arm is 8 weeks long with a 2-4 week washout period between treatments. A total of up to 30 participants with T2D will be recruited through outpatient clinics to allow for 24 completed participants available for assessment.

Participants will receive appropriate training by the research team on the safe use of the study devices (insulin pump and continuous glucose monitoring (CGM) and closed-loop insulin delivery system). Participants in the control arm will continue with standard therapy and will wear a blinded CGM system.

The primary outcome is time spent with glucose levels in the target range between 3.9 and 10.0 mmol/L as recorded by CGM. Secondary outcomes are the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics in addition to insulin requirements. Safety evaluation comprises the tabulation of severe hypoglycaemic episodes.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Device: CamAPS HX Closed-loop; Other: Multiple Daily Insulin Injections (Control)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Cambridge University Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years or over
2. Diagnosis of type 2 diabetes using standard diagnostic practice
3. Current treatment with subcutaneous insulin
4. Screening HbA1c ≤ 11% (97mmol/mol) on analysis from local laboratory
5. Subject is willing to perform regular finger-prick blood glucose monitoring
6. Willingness to wear study devices
7. Literate in English

Exclusion Criteria:

1. Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
2. Known or suspected allergy to insulin
3. Lack of reliable telephone facility for contact
4. Pregnancy, planned pregnancy, or breast feeding
5. Severe visual impairment
6. Severe hearing impairment
7. Medically documented allergy towards the adhesive (glue) of plasters
8. Serious skin diseases located at places of the body, which potentially are possible to be used for localisation of the glucose sensor
9. Illicit drugs abuse
10. Prescription drugs abuse
11. Alcohol abuse

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
Experimental: Closed loop insulin delivery; Unsupervised home use of day and night fully automated closed loop insulin delivery system (CamAPS HX) for 8 weeks The CamAPS HX closed-loop system comprises: Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) An Android smartphone hosting CamAPS HX Application with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump Glooko/Diasend cloud upload system to monitor CGM/insulin data	Device: CamAPS HX Closed-loop; The CamAPS HX closed-loop system comprises: Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) An Android smartphone hosting CamAPS HX Application with the Cambridge model predictive control algorithm and communicating wirelessly with the insulin pump Glooko/Diasend cloud upload system to monitor CGM/insulin data.
Active Comparator: Standard therapy; Participants in the control arm will continue to follow their current diabetes management plan for the 8 week study period. Participants will be wear a masked continuous glucose monitoring (CGM) system during the 8 week study period	Other: Multiple Daily Insulin Injections (Control); Multiple Daily Insulin Injections with masked Dexcom G6 CGM sensor (Dexcom, Northridge, CA, USA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in the target glucose range (3.9 to 10.0 mmol/l)	Percentage of time spent with sensor glucose readings in the target range from 3.9 to 10.0mmol/l	8 week intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent above target glucose (10.0 mmol/l)	Percentage of time spent with sensor glucose readings above target glucose (10.0 mmol/l)	8 week intervention period, both arms
Mean glucose	Mean sensor glucose level	8 week intervention period, both arms
Time spent in hypoglycaemia (<3.9 mmol/l)	Percentage of time spent with sensor glucose readings <3.9 mmol/L	8 week intervention period, both arms
Standard deviation of glucose levels	Standard deviation of glucose levels	8 week intervention period, both arms
Coefficient of variation of glucose levels	Coefficient of variation of glucose levels	8 week intervention period, both arms
Time spent below <3.0 mmol/l	Percentage of time spent with sensor glucose readings <3.0 mmol/l	8 week intervention period, both arms
Time in hyperglycaemia > 16.7 mmol/l	Percentage of time with glucose levels in hyperglycaemia > 16.7 mmol/l	8 week intervention period, both arms
Time in significant hyperglycaemia (> 20 mmol/l)	Percentage of time with glucose levels in significant hyperglycaemia (> 20 mmol/l)	8 week intervention period, both arms
Glycated haemoglobin (HbA1c)	HbA1c measured at the end of each study period	8 week intervention period, both arms
Total insulin dose	Average daily total insulin requirements	8 week intervention period, both arms

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of episodes of severe hypoglycaemia	Safety evaluation	8 week intervention period, both arms
Number of subjects experiencing severe hypoglycaemia	Safety evaluation	8 week intervention period, both arms
Frequency and nature of other adverse events or serious adverse events	Safety evaluation	8 week intervention period, both arms
Percentage of time of closed-loop operation	Utility evaluation	8 week intervention period, both arms
Percentage of time of CGM availability	Utility evaluation	8 week intervention period, both arms

Collaborators and Investigators

• Sponsor: University of Cambridge
• Investigators: Principal Investigator: Roman Hovorka, PhD, University of Cambridge

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2020
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: diabetes; type 2 diabetes; artificial pancreas; closed-loop; continuous glucose monitoring; insulin pump therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: RG97920

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Fully anonymised data may be shared with third parties (EU or non-EU based) for the purposes of advancing management and treatment of diabetes.

Drug and device information, study documents

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