Clinical trial NCT06579404: Closed-loop in Adults With Type 2 Diabetes
Official title: An Open-label, Multinational, Multicentre, Randomised, Single-period Parallel Study to Assess the Efficacy, Safety and Utility of Fully Closed-loop Insulin Delivery Compared to Standard Insulin Therapy With CGM in Adults With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Treated With Insulin
Keywords: Closed-loop insulin delivery
Type 2 diabetes
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: University of Edinburgh
name: Jaeb Center for Health Research
name: Swansea University
First posted: 2024-08-30
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multicentre, multinational, open-label, randomised single period, parallel design study contrasting fully closed-loop insulin delivery and standard insulin therapy with CGM over 26 weeks in adults with type 2 diabetes.
Primary purpose: TREATMENT

Brief 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.

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)

Eligibility criteria: 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:

* 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

Primary outcomes:
measure: Glycated haemoglobin (HbA1c) at 26 weeks
timeFrame: at 26 weeks
Secondary outcomes:
measure: Proportion of time spent in target glucose range (3.9 to 10.0mmol/L)
timeFrame: over 26 weeks
measure: Mean glucose (mmol/L)
timeFrame: over 26 weeks
measure: Proportion of time spent above target glucose (>10.0mmol/l)
timeFrame: over 26 weeks
measure: Proportion of time spent below target glucose (<3.9mmol/L)
timeFrame: over 26 weeks
measure: Standard deviation of sensor glucose
timeFrame: over 26 weeks
measure: Coefficient of variation of sensor glucose
timeFrame: over 26 weeks
measure: Proportion of time spent below target glucose (<3.5mmol/L)
timeFrame: over 26 weeks
measure: Proportion of time spent below target glucose (<3.0mmol/L)
timeFrame: over 26 weeks
measure: Proportion of time spent above target glucose (>13.9mmol/l)
timeFrame: over 26 weeks
measure: Proportion of time spent above target glucose (>16.7mmol/l)
timeFrame: over 26 weeks
measure: Proportion of time spent above target glucose (>20.0mmol/l)
timeFrame: over 26 weeks
measure: Proportion of participants with HbA1c <7.0% [53mmol/mol] (%)
timeFrame: at 26 weeks
measure: Proportion of participants with HbA1c <7.5% [58mmol/mol] (%)
timeFrame: at 26 weeks
measure: Total daily insulin dose
timeFrame: over 26 weeks
measure: Body weight
timeFrame: at 26 weeks
measure: Waist hip ratio
timeFrame: 26 weeks
measure: Body Mass Index (BMI)
timeFrame: 26 weeks
measure: Fasted lipid profile
timeFrame: 26 weeks
measure: Renal function
timeFrame: 26 weeks
measure: Renal function
timeFrame: 26 weeks
measure: Renal function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
measure: Liver function
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
city: Praha
country: Czechia
facility: Diabetes Centre, Institute of Clinical and Experimental Medicine
city: Toulouse
country: France
facility: CHU de Toulouse
city: Freiburg
country: Germany
facility: Medical Center - University of Freiburg
city: Bern
country: Switzerland
facility: Bern University Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust
city: Leicester
country: United Kingdom
facility: Leicester Diabetes Centre
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: King's College Hospital, King's College NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
Study officials:
affiliation: University of Cambridge
name: Roman Hovorka
role: PRINCIPAL_INVESTIGATOR
References: