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

• ClinicalTrials.gov Identifier: NCT04701424
• Recruitment Status: Recruiting
• First Posted: January 8, 2021
• Last Update Posted: January 8, 2021
• Sponsor: University of Cambridge
• Information provided by (Responsible Party): Dr Roman Hovorka, University of Cambridge

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes	Device: CamAPS HX Closed-loop; Other: Multiple Daily Insulin Injections (Control)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 16, 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Time in the target glucose range (3.9 to 10.0 mmol/l) [ Time Frame: 8 week intervention period ]
   Percentage of time spent with sensor glucose readings in the target range from 3.9 to 10.0mmol/l

Secondary Outcome Measures :

1. Time spent above target glucose (10.0 mmol/l) [ Time Frame: 8 week intervention period, both arms ]
   Percentage of time spent with sensor glucose readings above target glucose (10.0 mmol/l)
2. Mean glucose [ Time Frame: 8 week intervention period, both arms ]
   Mean sensor glucose level
3. Time spent in hypoglycaemia (<3.9 mmol/l) [ Time Frame: 8 week intervention period, both arms ]
   Percentage of time spent with sensor glucose readings <3.9 mmol/
4. Standard deviation of glucose levels [ Time Frame: 8 week intervention period, both arms ]
   Standard deviation of glucose levels
5. Coefficient of variation of glucose levels [ Time Frame: 8 week intervention period, both arms ]
   Coefficient of variation of glucose levels
6. Time spent below <3.0 mmol/l [ Time Frame: 8 week intervention period, both arms ]
   Percentage of time spent with sensor glucose readings <3.0 mmol/l
7. Time in significant hyperglycaemia (> 20 mmol/l) [ Time Frame: 8 week intervention period, both arms ]
   Percentage of time with glucose levels in significant hyperglycaemia (> 20 mmol/l)
8. Total, basal and bolus insulin dose [ Time Frame: 8 week intervention period, both arms ]
   Average daily total, basal and bolus insulin requirements
9. AUC of glucose below 3.5 mmol/l [ Time Frame: 8 week intervention period, both arms ]
   Area under the curve of sensor glucose readings below 3.5mmol/l

Other Outcome Measures:

1. Number of episodes of severe hypoglycaemia [ Time Frame: 8 week intervention period, both arms ]
   Safety evaluation
2. Number of subjects experiencing severe hypoglycaemia [ Time Frame: 8 week intervention period, both arms ]
   Safety evaluation
3. Frequency and nature of other adverse events or serious adverse events [ Time Frame: 8 week intervention period, both arms ]
   Safety evaluation
4. Percentage of time of closed-loop operation [ Time Frame: 8 week intervention period, both arms ]
   Utility evaluation
5. Percentage of time of CGM availability [ Time Frame: 8 week intervention period, both arms ]
   Utility evaluation

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Roman Hovorka, PhD; +44 (0)1223 762 862; rh347@cam.ac.uk

Locations

United Kingdom

Cambridge University Hospitals NHS Foundation Trust; Recruiting

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

Contact: Roman Hovorka, PhD +44 (0)1223 762 862 rh347@cam.ac.uk

Principal Investigator: Mark Evans, MD, PhD

Sub-Investigator: Aideen Daly, MD

Sub-Investigator: Charlotte Boughton, MD, PhD

Sponsors and Collaborators

University of Cambridge

Investigators

• Principal Investigator: Roman Hovorka, PhD; University of Cambridge

More Information

• Responsible Party: Dr Roman Hovorka, Professor of Metabolic Technology, University of Cambridge
• ClinicalTrials.gov Identifier: NCT04701424
• Other Study ID Numbers: RG97920
• First Posted: January 8, 2021
• Last Update Posted: January 8, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dr Roman Hovorka, University of Cambridge:

diabetes; type 2 diabetes; closed-loop; artificial pancreas; insulin pump therapy; continuous glucose monitoring

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs