taRgeting bEtA-Cell Function To achIeVe Remission of Type 2 diAbeTEs (REACTIVATE)

Targeting Beta-cell Function to Achieve Remission of Type 2 Diabetes (REACTIVATE). An Open-label, Single-centre, Randomised, Parallel Study to Assess the Efficacy, Safety and Utility of Fully Closed-loop Insulin Delivery in Achieving Remission of Diabetes Compared to Standard Therapy With a Glucose Sensor in Adults With Recent Onset Type 2 Diabetes

The main objective of the REACTIVATE study is to investigate whether a period of intensive insulin therapy using closed-loop technology, when combined with diet and lifestyle education, can restore beta-cell function and achieve remission of recent-onset type 2 diabetes.

This is a single-centre, open-label, randomised, parallel design study comparing up to 12 weeks of fully closed-loop insulin delivery to standard care with a glucose sensor in adults with recent-onset type 2 diabetes. The primary outcome is the number of participants achieving remission of diabetes at 52 weeks, defined as HbA1c below 48mmol/mol after 12 or more weeks off all diabetes medications.

Other key outcomes include area under the curve for C-peptide and glucose during mixed meal tolerance test, the proportion of time spent with glucose levels within and above the target glucose range and mean sensor glucose as recorded by glucose sensor at 52 weeks.

Safety evaluation comprises severe hypoglycaemic episodes, and other adverse and serious adverse events. Utility and human factors outcomes include glucose sensor and closed-loop usage, questionnaires and semi-structured interviews.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Device: Fully automated insulin delivery with CamAPS HX; Device: Standard diabetes therapy with a glucose sensor

Detailed Description

This is a single-centre, open-label, randomised, parallel design study comparing up to 12 weeks of fully closed-loop insulin delivery to standard care with a glucose sensor in adults with recent-onset type 2 diabetes.

Recruitment will target up to 56 participants to allow for drop-outs. Participants will be recruited from outpatient clinics at Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, local GP surgeries, social media advertising or other established practices at the centre. Written informed consent will be obtained from all participants before any study related activities.

After obtaining informed consent, the baseline visit (including mixed meal tolerance test) and a 2-3 week run-in period, participants will be randomised to either 12 weeks use of fully closed-loop insulin delivery or 12 weeks during which they will apply their standard diabetes therapy with a glucose sensor. Participants in both groups will receive diet and lifestyle advice with specific focus on the impact of diet and lifestyle choices on glucose sensor readings and trends.

Following the 12 weeks intervention period (and repeat mixed meal tolerance test) all participants will continue with standard diabetes therapy for nine months of follow-up (and final mixed meal tolerance test). Diabetes therapies will be adjusted every 3 months based on HbA1c.

The study includes up to 5 visits and 6 telephone/email contacts. Visits 2 and 3 may be combined. All participants will continue to be seen by their clinical team at frequencies as appropriate in line with usual clinical practice. All study visits will be scheduled in addition to routine clinical visits and will be performed by the research team. Maximum time in the study is 56 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charlotte K Boughton; Phone Number: +44 (0)1223 769066; Email: cb2000@cam.ac.uk

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Recruiting
      • Addenbrooke's Hospital NHS Foundation Trust
      • Contact: Charlotte Boughton; Phone Number: +441223769066; Email: cb2000@cam.ac.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 years and older
• Type 2 diabetes diagnosed >6 months and ≤5 years ago
• Treatment with glucose lowering medication for at least 3 months
• HbA1c >48 mmol/mol on analysis from local laboratory or equivalent
• Willing to wear study devices and follow study instructions
• Capacity to consent to participate in the study

Exclusion Criteria:

• Type 1 diabetes
• Current use of insulin pump
• Current use of any closed-loop system
• Any physical/psychological disease or medication(s) likely to interfere with the conduct of the study and interpretation of the study results, as judged by study clinician
• Known or suspected allergy against insulin
• Pregnancy, planned pregnancy, or breast feeding
• Severe visual or hearing impairment
• Medically documented allergy towards the adhesive of plasters
• Serious skin diseases located at places of the body potentially used for localisation of the glucose sensor
• Drug or alcohol misuse
• Group 2 driving licence holder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fully automated insulin delivery; Fully automated insulin delivery with CamAPS HX, Freestyle Libre 3 Sensor and Ypsopump insulin pump for 12 weeks	Device: Fully automated insulin delivery with CamAPS HX; Fully automated insulin delivery with CamAPS HX app, Libre 3 glucose sensor and Ypsopump insulin pump.
Active Comparator: Standard therapy with a glucose sensor; Standard diabetes therapy with a glucose sensor for 12 weeks	Device: Standard diabetes therapy with a glucose sensor; Standard diabetes therapy with a Freestyle Libre 3 glucose sensor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants achieving remission of diabetes at 52 weeks	The between group difference in the number of participants achieving remission of diabetes at 52 weeks, defined as HbA1c <48mmol/mol after ≥12 weeks off all diabetes medications.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Body weight (kg)	12 weeks
Blood pressure	Blood pressure (mmHg)	52 weeks
Mixed meal tolerance test (MMTT) area under the curve for C-peptide	Mixed meal tolerance test (MMTT) area under the curve for C-peptide	12 weeks
Mixed meal tolerance test (MMTT) area under the curve for C-peptide	Mixed meal tolerance test (MMTT) area under the curve for C-peptide	52 weeks
Mixed meal tolerance test (MMTT) area under the curve for glucose	Mixed meal tolerance test (MMTT) area under the curve for glucose	12 weeks
Mixed meal tolerance test (MMTT) area under the curve for glucose	Mixed meal tolerance test (MMTT) area under the curve for glucose	52 weeks
Proportion of time spent in tight target glucose range (3.9 to 7.8mmol/l)	Proportion of time spent with sensor glucose in tight target glucose range (3.9 to 7.8mmol/l)	12 weeks
Proportion of time spent in tight target glucose range (3.9 to 7.8mmol/l)	Proportion of time spent with sensor glucose in tight target glucose range (3.9 to 7.8mmol/l)	52 weeks
Proportion of time spent in target glucose range (3.9 to 10.0mmol/l)	Proportion of time spent with sensor glucose in target glucose range (3.9 to 10.0mmol/l)	12 weeks
Proportion of time spent intarget glucose range (3.9 to 10.0mmol/l)	Proportion of time spent with sensor glucose in target glucose range (3.9 to 10.0mmol/l)	52 weeks
Proportion of time spent below target glucose range (<3.9mmol/l)	Proportion of time spent below target glucose range (<3.9mmol/l)	12 weeks
Proportion of time spent below target glucose range (<3.9mmol/l)	Proportion of time spent below target glucose range (<3.9mmol/l)	52 weeks
Proportion of time spent above target glucose range (>10.0mmol/l)	Proportion of time spent above target glucose range (>10.0mmol/l)	12 weeks
Proportion of time spent above target glucose range (>10.0mmol/l)	Proportion of time spent above target glucose range (>10.0mmol/l)	52 weeks
Mean sensor glucose	Mean sensor glucose (mmol/l)	12 weeks
Mean sensor glucose	Mean sensor glucose (mmol/l)	52 weeks
Glycated haemoglobin	HbA1c (mmol/mol)	12 weeks
Glycated haemoglobin	HbA1c (mmol/mol)	52 weeks
Blood pressure	Blood pressure (mmHg)	12 weeks
Body weight	Body weight (kg)	52 weeks
Number of diabetes medications	Number of diabetes medications	52 weeks

Collaborators and Investigators

• Sponsor: University of Cambridge
• Collaborators: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Charlotte K Boughton, University of Cambridge

Study record dates

Study Major Dates

• Study Start (Estimated): April 24, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: closed-loop; Remission
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Physiological Effects of Drugs; Hypoglycemic Agents; Insulin
• Other Study ID Numbers: REACTIVATE 346139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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 cb2000@cam.ac.uk and may be submitted up to 36 months following article publication. To gain access, data requestors will need to sign a data access agreement.

Fully anonymised data may be shared with third parties (EU or non-EU based) for the purposes of advancing management and treatment of diabetes.

• IPD Sharing 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 cb2000@cam.ac.uk and may be submitted up to 36 months following article publication.
• IPD Sharing 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 cb2000@cam.ac.uk and may be submitted up to 36 months following article publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No