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RecruitingNCT06579404COYOTEUpdated Mar 13, 2026

Closed-loop in Adults With Type 2 Diabetes

An interventional study of CamAPS HX and Standard insulin therapy with glucose sensor in Type 2 Diabetes Treated With Insulin, sponsored by University of Cambridge. Recruiting at 12 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-13.

Sponsored by University of Cambridge · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
224
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The main objective of this study is to determine the efficacy, safety and utility of fully closed-loop glucose control in the home setting 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 2 diabetes in the inpatient and in the home setting and in children and adults with type 1 diabetes.

This is an open-label, multi-national, multi-centre, randomised, single-period parallel study, involving a run-in period followed by a 26-week intervention period during which glucose levels will be controlled either by a fully closed-loop system or by participants usual insulin therapy with continuous glucose monitoring. A total of up to 224 adults with type 2 diabetes using insulin will be recruited through outpatient diabetes clinics, primary care centres, social media advertising and other established methods at participating centres. Participants will receive appropriate training in the safe use of the study devices.

The primary outcome is the between group difference in HbA1c at 26 weeks. Other key outcomes include the time spent with glucose levels within, above and below the target glucose range (3.9-10.0mmol/L) and mean sensor glucose as recorded by CGM over the 26 weeks. Insulin requirements, body weight, renal and liver function will also be compared. Safety evaluation comprises severe hypoglycaemic episodes, and other adverse and serious adverse events. Human factors outcomes include CGM \& closed-loop usage, questionnaires and semi-structured interviews.

Read the detailed description

Purpose of clinical trial:

To determine the efficacy, safety and utility of fully closed-loop insulin delivery over 26 weeks in the home setting in adults with type 2 diabetes.

Study objectives:

To determine the efficacy, safety and utility of fully closed-loop insulin delivery over 26 weeks in the home setting in adults with type 2 diabetes.

  1. EFFICACY: The objective is to assess the ability of fully closed-loop insulin delivery to improve glucose control as measured by HbA1c (primary endpoint) and sensor glucose metrics.
  2. SAFETY: The objective is to evaluate the safety of fully closed-loop insulin delivery in terms of episodes and severity of hypoglycaemia, and nature and severity of other adverse events.
  3. UTILITY: The objective is to determine the acceptability and duration of use of the CGM and closed-loop system.
  4. HUMAN FACTORS: The objective is to assess cognitive, emotional, and behavioural characteristics of participants and their response to the closed-loop system using validated questionnaires and semi-structured interviews.

    Participating clinical centres:

    UK - Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust. - Imperial College Healthcare NHS Trust, London

    - Manchester Royal Infirmary, Manchester University NHS Foundation Trust

    - King's College Hospital, King's College Hospital NHS Foundation Trust, London

    - Guy's and St Thomas' NHS Foundation Trust

    - Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust

    - University Hospitals of Leicester NHS Trust

    Switzerland

    - Inselspital, Bern University Hospital, Bern

    France

    - Centre Hospitalier Universitaire (CHU) de Toulouse

    Germany

    - Medical Center - University of Freiburg

    Austria

    - Medical University of Graz, Graz

    Czech Republic

    - Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague

    Sample Size:

224 participants (112 per group) will be randomised. Recruitment will target a minimum quota of 25% of participants using basal insulin and a minimum quota of 60% of participants using multiple daily insulin injections.

Maximum duration of study for a subject: 30 weeks

Recruitment:

Participants will be recruited through outpatient diabetes clinics, primary care centres, social media advertising or other established methods at participating centres

Consent:

Participants will be asked to provide written informed consent.

Baseline Assessment:

Eligible participants will undergo baseline evaluation involving talking a medical history including demographics, height/weight, waist hip ratio and blood pressure measurement and blood samples for HbA1c, fasted lipid profile, renal and liver function. A urine albumin-creatinine ratio (ACR) will be performed, along with a urine pregnancy test in females of child-bearing age. Human factors questionnaires will be completed and a masked glucose sensor will be applied.

Run-in Period:

During a 2-3 week run-in period, participants will use their usual insulin therapy and wear a masked CGM system. At the end of the run-in period, for compliance, at least 10 days of CGM data needs to be recorded. CGM data during the run-in period will be used to assess baseline glucose control before the start of the intervention phase.

Randomisation:

Eligible participants will be randomised in a 1:1 ratio using central randomisation software to fully closed-loop or standard insulin therapy with CGM for 26 weeks. Randomisation will be stratified by site and baseline HbA1c.

Fully closed loop insulin delivery (intervention arm):

Following randomisation, participants in the closed-loop group will receive training on the study CGM, study insulin pump and closed-loop App during a 1-2 hour outpatient session. Competency on the use of the closed-loop system will be evaluated. Further training may be delivered as required. Participants will be advised to use the closed-loop system for the next 26 weeks.

Standard insulin therapy with CGM (control arm):

Following randomisation, participants in the control group will use their usual insulin therapy and the study CGM. Training on the use of the CGM will be provided. Participants will use standard insulin therapy and CGM for the next 26 weeks.

3 month study visit: Weight, waist hip ratio and blood pressure will be measured and a blood sample will be taken for measurement of HbA1c, fasted lipid profile, renal and liver function. Data from the closed-loop system and CGM system will be reviewed. Human factors questionnaires will be completed.

End of study assessments:

Weight, waist hip ratio and blood pressure will be measured and a blood sample will be taken for measurement of HbA1c, fasted lipid profile, renal and liver function. Urinary ACR will be measured. Human factors questionnaires will be completed and a subset of participants will participate in interviews. Study devices will be returned and participants will resume their usual insulin therapy and standard glucose monitoring.

Procedures for safety monitoring during trial:

Standard operating procedures for monitoring and reporting of all adverse events and adverse device events will be in place, including serious adverse events (SAE), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia.

A data safety and monitoring board (DSMB) will be informed of all serious adverse events and any unanticipated serious adverse device effects that occur during the study and will review compiled adverse event data at periodic intervals.

Criteria for withdrawal of subjects on safety grounds:

A participant may terminate participation in the study at any time without necessarily giving a reason and without any personal disadvantage. An investigator can stop the participation of a subject after consideration of the benefit/risk ratio. Possible reasons are:

  • Participant is unable to demonstrate safe use of study devices as judged by the investigator
  • Serious adverse events
  • Significant protocol violation or non-compliance
  • Decision by the investigator, or the Sponsor, that termination is in the participant's best medical interest
  • Pregnancy, planned pregnancy, or breast feeding
  • Allergic reaction to insulin or severe allergic reaction to adhesive surface of infusion set or glucose sensor
  • Technical grounds (e.g. participant relocates)
02

Conditions studied

  • Type 2 Diabetes Treated With Insulin

Keywords

  • Closed-loop insulin delivery
  • Type 2 diabetes
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Aged 18 years and older
  • Type 2 diabetes diagnosed for at least 12 months
  • Established on an SGLT2 inhibitor and/or GLP-1 receptor agonist for at least 3 months, or have been offered these therapies previously.
  • Treatment with insulin therapy for at least 6 months
  • HbA1c ≤ 15% (140 mmol/mol) 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

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
  • Medically documented allergy towards the adhesive
  • Pregnancy, planned pregnancy, or breast feeding
  • Severe visual impairment
  • Severe hearing impairment
  • Medically documented allergy towards the adhesive (glue) of plasters
  • Serious skin diseases located at places of the body, which potentially are possible to be used for localisation of the glucose sensor
  • Illicit drugs abuse
  • Prescription drugs abuse
  • Alcohol abuse
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
224 participants (estimated)

Study arms

  • Experimental
    Fully closed-loop insulin delivery (CamAPS HX)

    The automated closed loop system (CamAPS FX) will consist of: * YpsoPump insulin pump (Ypsomed, Burgdorf, Switzerland) * FreeStyle Libre 3 glucose sensor (Abbott Diabetes Care, CA, USA) * Smartphone hosting CamAPS HX app with the Cambridge model predictive control algorithm * Cloud upload system to review CGM/insulin data. Participants will use the fully closed-loop system for 26 weeks at home

    Device: CamAPS HX

  • Active comparator
    Standard insulin therapy with glucose sensor

    Usual insulin therapy and FreeStyle Libre 3 glucose sensor (Abbott Diabetes Care, CA, USA) for 26 weeks at home.

    Other: Standard insulin therapy with glucose sensor

Interventions

  • DeviceCamAPS HX

    The automated closed loop system (CamAPS HX) will consist of: YpsoPump insulin pump Freestyle Libre 3 glucose sensor Smartphone hosting CamAPS HX app with the Cambridge model predictive control algorithm

  • OtherStandard insulin therapy with glucose sensor

    Participants usual insulin therapy with Freestyle Libre 3 glucose sensor

05

What researchers measure

Primary outcomes

  1. Glycated haemoglobin (HbA1c) at 26 weeks

    Centralised measurement of HbA1c

    Time frame: at 26 weeks

Secondary outcomes

  1. Proportion of time spent in target glucose range (3.9 to 10.0mmol/L)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  2. Mean glucose (mmol/L)

    Sensor glucose metric measured in mmol/L

    Time frame: over 26 weeks

  3. Proportion of time spent above target glucose (>10.0mmol/l)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  4. Proportion of time spent below target glucose (<3.9mmol/L)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  5. Standard deviation of sensor glucose

    Sensor glucose metric measured in mmol/L

    Time frame: over 26 weeks

  6. Coefficient of variation of sensor glucose

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  7. Proportion of time spent below target glucose (<3.5mmol/L)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  8. Proportion of time spent below target glucose (<3.0mmol/L)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  9. Proportion of time spent above target glucose (>13.9mmol/l)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  10. Proportion of time spent above target glucose (>16.7mmol/l)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  11. Proportion of time spent above target glucose (>20.0mmol/l)

    Sensor glucose metric measured as a %

    Time frame: over 26 weeks

  12. Proportion of participants with HbA1c <7.0% [53mmol/mol] (%)

    Binary metric of HbA1c

    Time frame: at 26 weeks

  13. Proportion of participants with HbA1c <7.5% [58mmol/mol] (%)

    Binary metric of HbA1c

    Time frame: at 26 weeks

  14. Total daily insulin dose

    Measured in units/day

    Time frame: over 26 weeks

  15. Body weight

    Measured in kilograms

    Time frame: at 26 weeks

  16. Waist hip ratio

    Ratio

    Time frame: 26 weeks

  17. Body Mass Index (BMI)

    Measured in kg/m2

    Time frame: 26 weeks

  18. Blood Pressure (mmHg)

    Time frame: 26 weeks

  19. Fasted lipid profile

    Measured in mmol/L

    Time frame: 26 weeks

  20. Renal function

    Renal function as measured by serum creatinine

    Time frame: 26 weeks

  21. Renal function

    Renal function as measured by estimated Glomerular Filtration Rate

    Time frame: 26 weeks

  22. Renal function

    Renal function as measured by urinary albumin creatinine ratio

    Time frame: 26 weeks

  23. Liver function

    Liver function as measured by FIB4 index

    Time frame: 26 weeks

  24. Liver function

    Liver function as measured by alanine transaminase (ALT)

    Time frame: 26 weeks

  25. Liver function

    Liver function as measured by aspartate transaminase (AST)

    Time frame: 26 weeks

  26. Liver function

    Liver function as measured by alkaline phosphatase (ALP)

    Time frame: 26 weeks

  27. Liver function

    Liver function as measured by gamma-glutamyl transferase (yGT)

    Time frame: 26 weeks

  28. Liver function

    Liver function as measured by serum bilirubin

    Time frame: 26 weeks

  29. Liver function

    Liver function as measured by albumin

    Time frame: 26 weeks

  30. Number of severe hypoglycaemia events

    Time frame: 26 weeks

  31. Number of participants with any severe hypoglycaemia event

    Time frame: 26 weeks

  32. Number of diabetic ketoacidosis events

    Time frame: 26 weeks

  33. Number of participants with any diabetic ketoacidosis event

    Time frame: 26 weeks

  34. Number of adverse events per participant

    Time frame: 26 weeks

  35. Number of serious adverse events per participant

    Time frame: 26 weeks

  36. Proportion of CGM use (%)

    Time frame: 26 weeks

  37. Proportion of closed-loop use (%)

    Time frame: 26 weeks

06

Study locations

5 of 12 sites recruiting
  • University of Melbourne
    Melbourne, Australia
    • David O'Neal · Contact
    Not yet recruiting
  • Medical University of Graz
    Graz, Austria
    • Julia Mader · Contact
    Not yet recruiting
  • Diabetes Centre, Institute of Clinical and Experimental Medicine
    Prague, Czechia
    • Martin Haluzík · Contact
    Not yet recruiting
  • CHU de Toulouse
    Toulouse, France
    • Hélène Hanaire · Contact
    Not yet recruiting
  • Bern University Hospital
    Bern, Switzerland
    • Lia Bally · Contact
    Not yet recruiting
  • Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
    Cambridge, United Kingdom
    • Charlotte Boughton · Contact
    Recruiting
  • Royal Derby Hospital
    Derby, United Kingdom
    • Emma Wilmot · Contact
    Not yet recruiting
  • Leicester Diabetes Centre
    Leicester, United Kingdom
    • Pratik Choudhary · Contact
    Recruiting
  • Guy's and St Thomas' NHS Foundation Trust
    London, United Kingdom
    • Sufyan Hussain · Contact
    Recruiting
  • King's College Hospital, King's College NHS Foundation Trust
    London, United Kingdom
    • Yee Cheah · Contact
    Recruiting
  • Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust
    Manchester, United Kingdom
    • Hood Thabit · Contact
    Not yet recruiting
  • Norfolk and Norwich University Hospital
    Norwich, United Kingdom
    • Sankalpa Neupane · Contact
    Recruiting
07

References and documents

Publications

  • Seese R, Boughton CK, Tseung FT, Uy R, Wilinska ME, Thabit H, Cheah YS, Neupane S, Hussain S, Choudhary P, Wilmot EG, Bally L, Hanaire H, Mader JK, Haluzik M, O'Neal D, Lawton J, Rankin D, Kollman C, Dunseath G, Hovorka R. Assessing the efficacy, safety and utility of fully closed-loop insulin delivery compared to standard insulin therapy with a continuous glucose monitor in adults with type 2 diabetes (COYOTE study): a randomised parallel study protocol. BMJ Open. 2026 May 19;16(5):e115464. doi: 10.1136/bmjopen-2025-115464. PubMed 42156154 ↗

Individual participant data

Plan to share: Yes — 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. 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.

Supporting information: Study protocol, Sap

08

Registry details

Key details

Study ID
NCT06579404
Lead sponsor
University of Cambridge
Collaborators
University of Edinburgh, Jaeb Center for Health Research, Swansea University
Responsible party
Dr Roman Hovorka (Professor of Metabolic Technology, University of Cambridge) — Principal investigator
First posted
Aug 30, 2024
Start date
Dec 6, 2024
Primary completion
Mar 2027 (estimated)
Completion
Jul 2027 (estimated)
Last update
Mar 13, 2026

Study contacts

Charlotte K Boughton, PhD
Contact
cb2000@medschl.cam.ac.uk
+44 (0)1223 769066
Angel Tseung
Contact
ftt20@cam.ac.uk
Roman Hovorka
principal investigator · University of Cambridge

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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