Closing the Loop in Adults With Type 1 Diabetes (CLEAR)

NCT04977908 | Completed DMC

• 1 other identifier: 291543
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this study is to determine whether home use of fully closed-loop glucose control applying ultra-rapid Lispro insulin is superior to standard insulin pump therapy with continuous glucose monitoring (CGM) in adults with type 1 diabetes on insulin pump therapy with sub-optimal glycaemic control (HbA1c ≥ 8.0%). This is an open-label, single centre, randomised, crossover design study, involving a run-in period followed by two study periods during which glucose levels will be controlled either by an automated closed-loop system using ultra-rapid Lispro insulin or by participants usual insulin pump therapy with continuous glucose monitoring in random order. A total of up to 30 adults (aiming for 24 completed participants) with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods. Participants who drop out of the study within the first 4 weeks of the first intervention arm will be replaced. Participants will receive appropriate training in the safe use of the closed-loop devices. Participants will have access to the study team during the home study phase with 24/7 telephone support. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM over the 8 week period. Secondary outcomes are HbA1c, 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 severe hypoglycaemic episodes, diabetic ketoacidosis (DKA) events and other adverse and serious adverse events.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• Time in target glucose range

  Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on continuous glucose monitoring (CGM)

  8-week home use

Secondary Outcomes (8)

• Time spent above the target glucose range

  8-week home use

• Time spent below the target glucose range

  8-week home use

• Mean glucose

  8-week home use

• Standard deviation and coefficient of variation of glucose

  8-week home use

• Time spent in hypoglycaemia

  8-week home use

Other Outcomes (3)

• Safety evaluation

  8-week home use

• Utility evaluation

  8-week home use

• Human Factor assessment

  8-week home use

Study Arms (2)

Fully closed-loop system with ultra-rapid Lispro insulin

EXPERIMENTAL

The fully closed-loop system (CamAPS HX) will consist of: * Dana insulin pump (Diabecare, Sooil, Seoul, South Korea) * Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA) * An Android smartphone hosting CamAPS HX app with the Cambridge model predictive control algorithm * Cloud upload system to review CGM/insulin data. Participants will use ultra-rapid Lispro insulin in the closed-loop system

Device: CamAPS HX

Standard insulin pump therapy with CGM

ACTIVE COMPARATOR

Participants will use their own insulin pump and usual insulin throughout this study period. The CGM will be the Dexcom G6 real-time CGM sensor (Dexcom, Northridge, CA, USA)

Device: Standard insulin pump therapy with CGM

Interventions

CamAPS HX DEVICE

Fully automated closed-loop system (CamAPS HX) with ultra-rapid Lispro insulin

Fully closed-loop system with ultra-rapid Lispro insulin

Standard insulin pump therapy with CGM DEVICE

Participants usual insulin pump therapy with Dexcom G6 CGM

Standard insulin pump therapy with CGM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant has type 1 diabetes as defined by WHO for at least 1 year
• The participant is 18 years of age or older
• The participant will have been on an insulin pump for at least 6 months with good knowledge of insulin self-adjustment
• The participant is treated with one of the rapid acting or ultra-rapid acting insulin analogues (Insulin Aspart, faster acting insulin Aspart, Insulin Lispro, ultra-rapid Lispro insulin or Insulin Glulisine)
• HbA1c ≥8.0% (64 mmol/mol) based on analysis from local laboratory
• The participant is willing to wear closed-loop devices
• The participant is willing to follow study specific instructions
• Female participants of child bearing age should using effective contraception and must have a negative urine-HCG pregnancy test at screening.

You may not qualify if:

• Any physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
• Known or suspected allergy against insulin
• Total daily insulin dose \> 2 IU/kg/day
• Use of a closed-loop system within the past 30 days
• Participant is pregnant or breast feeding or planning pregnancy within next 12 months
• Severe visual impairment
• Severe hearing impairment
• Lack of reliable telephone facility for contact
• Participant not proficient in English

Sponsors & Collaborators

• University of Cambridge: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (2)

• Lakshman R, Hartnell S, Ware J, Allen JM, Wilinska ME, Nwokolo M, Evans ML, Hovorka R, Boughton CK. Lived Experience of Fully Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes. Diabetes Technol Ther. 2024 Apr;26(4):211-221. doi: 10.1089/dia.2023.0394. Epub 2024 Feb 28.

  PMID: 38426909 DERIVED

• Boughton CK, Hartnell S, Lakshman R, Nwokolo M, Wilinska ME, Ware J, Allen JM, Evans ML, Hovorka R. Fully Closed-Loop Glucose Control Compared With Insulin Pump Therapy With Continuous Glucose Monitoring in Adults With Type 1 Diabetes and Suboptimal Glycemic Control: A Single-Center, Randomized, Crossover Study. Diabetes Care. 2023 Nov 1;46(11):1916-1922. doi: 10.2337/dc23-0728.

  PMID: 37616583 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Continuous Glucose Monitoring

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Monitoring, Physiologic; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Metabolic Technology

Model Details: An open-label, single-centre, randomised, two-period, crossover study comparing closed-loop glucose control compared to standard insulin pump therapy combined with continuous glucose monitoring

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: July 27, 2021
• Study Start: August 31, 2021
• Primary Completion: March 31, 2023
• Study Completion: May 31, 2023
• Last Updated: November 21, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication.
• Access Criteria: Study protocol, statistical analysis plan and fully anonymised individual participant data that underlie the results reported in the manuscript will be available 6 months following publication and ending 36 months following manuscript publication to investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose, to achieve aims in the approved proposal. Proposals should be directed to rh347@cam.ac.uk and may be submitted up to 36 months following article publication.

Locations

GB (1)