Type 1 Diabetes MellitusPhase 2NCT01440140
Closing the Loop in Adults With Type 1 Diabetes in the Home Setting
A Phase 2 study testing Closed-loop and Conventional insulin pump delivery in people with Type 1 Diabetes Mellitus, run by University of Cambridge at 3 sites in United Kingdom.
Trial summary
The main study objective is to compare real-time continuous subcutaneous glucose monitoring (CGM) combined with overnight automated closed-loop glucose control, and real-time CGM alone in the home setting. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Closed-loop and Conventional insulin pump delivery
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Dec 2012to Jan 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes, as defined by WHO for at least 6 months or confirmed C-peptide negative.
- On insulin pump therapy for at least 3 months
Who cannot join
- Non-type 1 diabetes mellitus
- Any physical/psychological disease likely to interfere with the study
- Taking medication likely to interfere with interpretation of the results
- Known/suspected allergy against insulin
- Patients with clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator
- Ongoing severe recurrent hypoglycaemia as judged by the investigator.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Addenbrooke's Hospital
Cambridge, CB2 0QQ
King's College London
London, SE5 9RJ
Northern General Hospital
Sheffield, S5 7AU
About this study
Official title: An Open-label, Three-centre, Randomised, Two-period, Crossover Study to Assess the Efficacy, Safety and Utility of Real-time Continuous Subcutaneous Glucose Monitoring Combined With Overnight Closed-loop Glucose Control in the Home Setting in Comparison With Real-time Continuous Subcutaneous Glucose Monitoring Alone in Adults With Type 1 Diabetes on Subcutaneous Insulin Infusion Pump Therapy
The main study objective is to compare real-time continuous subcutaneous glucose monitoring (CGM) combined with overnight automated closed-loop glucose control, and real-time CGM alone in the home setting.
Read the detailed description
Achievement of tight glycaemic control in type 1 diabetes mellitus (T1D) using intensive insulin regimens, which has been shown to be important for the prevention of long term diabetes-related complications, is limited by a significantly increased risk of hypoglycaemia. The average patient with T1D suffers two symptomatic episodes of hypoglycaemia per week, and one episode of severe hypoglycaemia, defined as an event requiring assistance of another person to administer rescue treatment in the form of carbohydrate and/or glucagon, per year.Despite the rapid advancements in insulin pump technology and the ongoing development of more physiological insulin preparations, the currently available therapeutic regimens are still unable to achieve optimal glycaemic control.The emergence of continuous glucose monitoring (CGM) over the last decade, which enables users to view in real-time estimates of plasma glucose and receive alarms for impending hypo- or hyperglycaemia, thus facilitating appropriate changes in insulin therapy, is a major step towards improved diabetes monitoring.
The desirable goal is the development of an insulin delivery that is glucose responsive and the development of effective real time glucose monitoring should allow this. Glucose responsive insulin delivery should allow achievement of ideal glucose targets with less risk of hypoglycaemia. Closed-loop systems may provide a realistic treatment option for people with T1D. The research we are conducting at the University of Cambridge has been focused on developing a closed-loop system for overnight glucose control in patients with T1D. The studies that have been performed so far employ model predictive control (MPC) - this algorithm estimates patient-specific parameters from CGM measurements taken every 1 to 15 minutes and makes predictions of glucose excursions, which are then used to calculate basal insulin infusion rates. We hypothesize that overnight automated closed-loop glucose control in the home setting will be efficacious and safe compared to CGM alone, in T1D subjects on insulin pump treatment.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Closed-loop, Conventional insulin pump delivery
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Closed-loopOther
Also called Automated CL
Subcutaneous delivery of Novorapid insulin, dose calculated by control algorithm, based on continuous glucose sensor readings.
Conventional insulin pump deliveryOther
Subcutaneous delivery of Novorapid insulin according to usual pump regime
| Study group | Role | What they receive |
|---|---|---|
| Closed loop (algorithm) | Experimental | Not described Receives: Other: Closed-loop |
| Open loop | Placebo comparator | Not described Receives: Other: Conventional insulin pump delivery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of CGM (Continuous glucose monitoring) values in target (3.9 - 8.0 mmol/l).
Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm.
Measured: 4 weeks
Secondary outcomes (3)
Percentage of CGM values below 3.9 mmol/l.
Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm.
Measured: 4 weeks
Time spent with glucose levels below 3.9 mmol/l and above 8.0 mmol/l, as recorded by CGM and other CGM-based metrics
Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm.
Measured: 4 weeks
Glycaemic control assessed by fructosamine and HbA1c
Participants will be assessed for 4 weeks in each arm.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2011 (estimated)
- Study startDec 2012
- Primary completionDec 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Diabetes UK
- Responsible party
- Principal investigator, Hood Thabit, University of Cambridge
- Investigators
- Roman Hovorka, PhD, MSc, BSc, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01440140
- Sponsor's protocol ID
- ANGELA03
- Status last verified
- Jan 2014
- First submitted
- 20 Sep 2011
- Last updated
- 29 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Thabit H, Elleri D, Leelarathna L, Allen J, Lubina-Solomon A, Stadler M, Walkinshaw E, Iqbal A, Choudhary P, Wilinska M, Barnard K, Heller S, Amiel S, Evans M, Dunger D, Hovorka R. Unsupervised overnight closed loop insulin delivery during free living: analysis of randomised cross-over home studies in adults and adolescents with type 1 diabetes. Lancet. 2015 Feb 26;385 Suppl 1:S96. doi: 10.1016/S0140-6736(15)60411-1.
PubMed 26312919Thabit H, Leelarathna L, Wilinska ME, Elleri D, Allen JM, Lubina-Solomon A, Walkinshaw E, Stadler M, Choudhary P, Mader JK, Dellweg S, Benesch C, Pieber TR, Arnolds S, Heller SR, Amiel SA, Dunger D, Evans ML, Hovorka R. Accuracy of Continuous Glucose Monitoring During Three Closed-Loop Home Studies Under Free-Living Conditions. Diabetes Technol Ther. 2015 Nov;17(11):801-7. doi: 10.1089/dia.2015.0062. Epub 2015 Aug 4.
PubMed 26241693Thabit H, Lubina-Solomon A, Stadler M, Leelarathna L, Walkinshaw E, Pernet A, Allen JM, Iqbal A, Choudhary P, Kumareswaran K, Nodale M, Nisbet C, Wilinska ME, Barnard KD, Dunger DB, Heller SR, Amiel SA, Evans ML, Hovorka R. Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study. Lancet Diabetes Endocrinol. 2014 Sep;2(9):701-9. doi: 10.1016/S2213-8587(14)70114-7. Epub 2014 Jun 16.
PubMed 24943065
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Three-centre, Randomised, Two-period, Crossover Study to Assess the Efficacy, Safety and Utility of Real-time Continuous Subcutaneous Glucose Monitoring Combined With Overnight Closed-loop Glucose Control in the Home Setting in Comparison With Real-time Continuous Subcutaneous Glucose Monitoring Alone in Adults With Type 1 Diabetes on Subcutaneous Insulin Infusion Pump Therapy
- ClinicalTrials.gov ID
- NCT01440140
- Acronym / sponsor ID
- ANGELA03
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Diabetes UK
- Study start
- Dec 2012
- Primary completion
- Dec 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 26 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main study objective is to compare real-time continuous subcutaneous glucose monitoring (CGM) combined with overnight automated closed-loop glucose control, and real-time CGM alone in the home setting.
Detailed description
Achievement of tight glycaemic control in type 1 diabetes mellitus (T1D) using intensive insulin regimens, which has been shown to be important for the prevention of long term diabetes-related complications, is limited by a significantly increased risk of hypoglycaemia. The average patient with T1D suffers two symptomatic episodes of hypoglycaemia per week, and one episode of severe hypoglycaemia, defined as an event requiring assistance of another person to administer rescue treatment in the form of carbohydrate and/or glucagon, per year.Despite the rapid advancements in insulin pump technology and the ongoing development of more physiological insulin preparations, the currently available therapeutic regimens are still unable to achieve optimal glycaemic control.The emergence of continuous glucose monitoring (CGM) over the last decade, which enables users to view in real-time estimates of plasma glucose and receive alarms for impending hypo- or hyperglycaemia, thus facilitating appropriate changes in insulin therapy, is a major step towards improved diabetes monitoring.
The desirable goal is the development of an insulin delivery that is glucose responsive and the development of effective real time glucose monitoring should allow this. Glucose responsive insulin delivery should allow achievement of ideal glucose targets with less risk of hypoglycaemia. Closed-loop systems may provide a realistic treatment option for people with T1D. The research we are conducting at the University of Cambridge has been focused on developing a closed-loop system for overnight glucose control in patients with T1D. The studies that have been performed so far employ model predictive control (MPC) - this algorithm estimates patient-specific parameters from CGM measurements taken every 1 to 15 minutes and makes predictions of glucose excursions, which are then used to calculate basal insulin infusion rates. We hypothesize that overnight automated closed-loop glucose control in the home setting will be efficacious and safe compared to CGM alone, in T1D subjects on insulin pump treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Closed loop (algorithm) | Experimental | Other: Closed-loop |
| Open loop | Placebo comparator | Other: Conventional insulin pump delivery |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Type 1 diabetes, as defined by WHO for at least 6 months or confirmed C-peptide negative.
- On insulin pump therapy for at least 3 months
Key exclusion criteria (6 listed)
- Non-type 1 diabetes mellitus
- Any physical/psychological disease likely to interfere with the study
- Taking medication likely to interfere with interpretation of the results
- Known/suspected allergy against insulin
- Patients with clinically significant nephropathy, neuropathy or retinopathy as judged by the investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Closed-loopAlso: Automated CLSubcutaneous delivery of Novorapid insulin, dose calculated by control algorithm, based on continuous glucose sensor readings. | Other | Closed loop (algorithm) |
| Conventional insulin pump deliverySubcutaneous delivery of Novorapid insulin according to usual pump regime | Other | Open loop |
Primary outcome
Percentage of CGM (Continuous glucose monitoring) values in target (3.9 - 8.0 mmol/l).
Time frame: 4 weeks
Participants will be assessed overnight (00:00 to 07:00) for 4 weeks in each arm.
3 secondary outcomes
Percentage of CGM values below 3.9 mmol/l.
Time frame: 4 weeks
Time spent with glucose levels below 3.9 mmol/l and above 8.0 mmol/l, as recorded by CGM and other CGM-based metrics
Time frame: 4 weeks
Glycaemic control assessed by fructosamine and HbA1c
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2014.
- Derived from this study: PubMed 26312919Thabit H, Elleri D, Leelarathna L, Allen J, Lubina-Solomon A, Stadler M, Walkinshaw E, Iqbal A, Choudhary P, Wilinska M, Barnard K, Heller S, Amiel S, Evans M, Dunger D, Hovorka R. Unsupervised overnight closed loop insulin delivery during free living: analysis of randomised cross-over home studies in adults and adolescents with type 1 diabetes. Lancet. 2015 Feb 26;385 Suppl 1:S96. doi: 10.1016/S0140-6736(15)60411-1.
- Derived from this study: PubMed 26241693Thabit H, Leelarathna L, Wilinska ME, Elleri D, Allen JM, Lubina-Solomon A, Walkinshaw E, Stadler M, Choudhary P, Mader JK, Dellweg S, Benesch C, Pieber TR, Arnolds S, Heller SR, Amiel SA, Dunger D, Evans ML, Hovorka R. Accuracy of Continuous Glucose Monitoring During Three Closed-Loop Home Studies Under Free-Living Conditions. Diabetes Technol Ther. 2015 Nov;17(11):801-7. doi: 10.1089/dia.2015.0062. Epub 2015 Aug 4.
- Derived from this study: PubMed 24943065Thabit H, Lubina-Solomon A, Stadler M, Leelarathna L, Walkinshaw E, Pernet A, Allen JM, Iqbal A, Choudhary P, Kumareswaran K, Nodale M, Nisbet C, Wilinska ME, Barnard KD, Dunger DB, Heller SR, Amiel SA, Evans ML, Hovorka R. Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study. Lancet Diabetes Endocrinol. 2014 Sep;2(9):701-9. doi: 10.1016/S2213-8587(14)70114-7. Epub 2014 Jun 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman Hovorka, PhD, MSc, BSc principal investigator
University of Cambridge
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Closed-loop and Conventional insulin pump delivery in people with Type 1 Diabetes Mellitus, run by University of Cambridge at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of CGM (Continuous glucose monitoring) values in target (3.9 - 8.0 mmol/l). (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01440140, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2014.