Diabetes MellitusAPCam11NCT02523131
Home Testing of Day and Night Closed Loop With Pump Suspend Feature
A study testing FlorenceM and Medtronic insulin pump 640G in people with Diabetes Mellitus and Diabetes Mellitus, Type 1, run by University of Cambridge at 8 sites in 2 countries.
Trial summary
The main study objective is to determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy alone. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders
- What is being tested?
- FlorenceM and Medtronic insulin pump 640G
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 8 sitesin 2 countries
- Study dates
- May 2016to Mar 2018
- Phase
- Interventional
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The subject is at least 6 years or older [with equal proportion of youth (6 to 21 years) and adults (22 years and older)]
- The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative
- The subject will have been an insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator
- The subject is treated with one of the rapid acting insulin analogues (insulin Aspart, Lispro or Glulisine)
- The subject is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day
- Screening HbA1c ≥ 7.5% (58.5mmol/mol) and ≤ 10 % (86mmol/mol) based on analysis from local laboratory or equivalent [with equal proportion of subjects above and below HbA1c 8.5% (69mmol/mol)]
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- The subject is literate in English
- The subject is willing to wear glucose sensor
- The subject is willing to wear closed loop system at home
- The subject is willing to follow study specific instructions
- The subject is willing to upload pump and CGM data at regular intervals
- The subject is willing to restrict alcohol consumption to ≤ 2 units per day throughout the study period
- Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening.
- The subject lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance.
- The subject has access to WIFi at home.
Who cannot join
- Non-type 1 diabetes mellitus including those secondary to chronic disease
- Subject using real-time CGM on regular basis in preceding 3 months
- Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- Untreated coeliac disease or thyroid disease or subject is being treated for hypothyroidism at time of screening
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
- Known or suspected allergy to insulin
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- Subjects with clinically significant nephropathy (eGFR < 45ml/min) or on dialysis, neuropathy or active retinopathy (defined as presence of maculopathy or proliferative changes) as judged by the investigator
- Adults: one or more episodes of severe hypoglycaemia as defined by American Diabetes Association (33) in preceding 6 months; Youth: recurrent incidents of severe hypoglycaemia during the previous 6 months (Adults and adolescents: severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions including episodes of hypoglycaemia severe enough to cause unconsciousness, seizures or attendance at hospital; children: severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness);
- Random C-peptide > 100pmol/l with concomitant plasma glucose >4 mmol/l (72 mg/dl)
- Regular use of acetaminophen
- Lack of reliable telephone facility for contact
- Total daily insulin dose ≥ 2 IU/kg/day
- Total daily insulin dose < 15 IU/day
- Pregnancy, planned pregnancy, or breast feeding
- Severe visual impairment
- Severe hearing impairment
- Significantly reduced hypoglycaemia awareness in subjects 18 year and older (screening Gold score > 4)
- Subjects using implanted internal pace-maker
- Patients with medically documented allergy towards the adhesive (glue) of plasters or Subject is unable to tolerate tape adhesive in the area of sensor placement
- Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor)
- Subject is currently abusing illicit drugs
- Subject is currently abusing prescription drugs
- Subject is currently abusing alcohol
- Subject is using pramlintide (Symlin) at time of screening
- Subject has elective surgery planned that requires general anaesthesia during the course of the study
- Subject is a shift worker with working hours between 10pm and 8am
- Subject has a sickle cell disease, haemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
- Subject diagnosed with current eating disorder such as anorexia or bulimia
- Subject plans to use significant quantity of herbal preparations (use of over the counter herbal preparation for 30 consecutive days or longer period during the study) or significant quantity of vitamin supplements (four times the recommended daily allowance used for 30 consecutive days or longer period during the study) during the course of their participation in the study
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United Kingdom5 sites
University of Cambridge
Cambridge, CB2 0QQ
Wellcome Trust-MRC Institute of Metabolic Science
Cambridge, CB2 0QQ
Royal Hospital for Sick Children
Edinburgh, EH9 1LF
Leeds Teaching Hospitals
Leeds, LS9 7TF
Manchester Diabetes Centre, Manchester Royal Infirmary
Manchester
United States3 sites
University of Colorado Denver
Aurora, Colorado, 80045
International Diabetes Center at Park Nicollet
Minneapolis, Minnesota, 55416
International Diabetes Centre at Park Nicollet
Minneapolis, Minnesota, 55416
About this study
Official title: An Open-label, Multi-centre, Randomised, Single-period, Parallel Design Study to Assess the Efficacy, Safety, Utility and Psychosocial Effect of 12 Week Day and Night Automated Closed Loop Glucose Control Combined With Pump Suspend Feature Compared to Sensor Augmented Insulin Pump Therapy in Youth and Adults With Type 1 Diabetes With Sub-optimal Glucose Control Under Free Living Conditions
The main study objective is to determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy alone.
This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a three-month period of home study during which day and night glucose levels will be controlled either by a closed loop system combined with pump suspend feature (intervention group) or by sensor augmented insulin pump therapy (control group).
Read more
It is expected that up to 100 subjects, aiming for 84 randomised subjects [42 youth (6 to 21 years), and 42 adults (22 years and older)], with type 1 diabetes will be recruited through paediatric and adult outpatient diabetes clinics in each of the investigation centres. Subjects who drop out within the first four weeks of the intervention may be replaced. Participants will all be on subcutaneous insulin pump therapy and will have proven competencies both in the use of the study insulin pump and the study CGM device.
Subjects in the intervention group will receive appropriate training in the safe use of closed loop insulin delivery system and pump suspend feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in the time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels during the 12 week free living phase. Secondary outcomes are HbA1 at the end of treatment period, the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes.
Read the detailed description
Purpose of the study:
To determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy.
Study objectives:
- EFFICACY: The objective is to assess efficacy of day and night automated closed loop glucose control combined with pump suspend feature in maintaining glucose levels within the target range from 3.9 to 10.0mmol/l (70 to 180mg/dl) based on subcutaneous continuous glucose monitoring (CGM), as compared to sensor augmented insulin pump therapy.
- SAFETY: The objective is to evaluate the safety of day and night automated closed loop glucose control combined with pump suspend feature, in terms of episodes of severe hypoglycaemia and other adverse events.
- UTILITY: The objective is to determine the frequency and duration of the use of the automated closed loop system.
- PSYCHOSOCIAL: Subjects' and family members' perception in terms of life-style change, diabetes management and fear of hypoglycaemia will be assessed using validated questionnaires and semi-structured qualitative interviews. Cognitive functions will be assessed using validated computerized cognitive tests.
Study design:
An open-label, multi-centre, multi-national, randomised, single-period, parallel group study, contrasting day and night automated closed loop glucose control combined with pump suspend feature with sensor augmented insulin pump therapy
Population:
84 participants randomised (42 youth and 42 adults). Each centre will aim to recruit between 05 and 20 participants.
Maximum duration of study for a subject :
18 weeks
Recruitment:
The subjects will be recruited through the paediatric and adult diabetes outpatient clinics at each centre.
Consent:
Written consent/assent will be obtained from participants and/or guardians according to REC/IRB requirements.
Screening assessment:
Eligible participants will undergo a screening evaluation where blood samples for full blood count, renal, liver, thyroid function and anti-transglutaminase antibodies with IgA levels will be taken (if not done in the previous 3 months). Random C-peptide, glucose and HbA1c will also be measured, and a urine pregnancy test in females of child-bearing potential.
Questionnaires investigating participants' quality of life, psychosocial functioning and response to their current treatment will be distributed. Cognitive assessment will be made using validated computerized cognitive tests.
Study Training:
Training sessions on the use of study CGM, insulin pump (and closed loop system for those randomised to the intervention group) will be provided by the research team. Training session on the use of real-time CGM and on how to interpret real-time and retrospective stored data will be provided to all subjects/carers using written material.
Run-in Period:
During a 4 week run-in period, subjects will use study CGM and insulin pump. The research team will contact subject once weekly during the run-in period, and subjects will also be able to contact the research team for support and treatment optimisation as necessary. For compliance and to assess the ability of the subject to use the CGM and study pump safely, at least 12 days of CGM data need to be recorded and safe use of study insulin pump demonstrated during the last 14 days of run-in period.
Competency assessment:
Competency on the use of study insulin pump and study CGM will be evaluated using a competency assessment tool developed by the research team. Further training may be delivered as required.
Randomisation:
Eligible subjects will be randomised using randomisation software to the use of real-time CGM and pump suspend feature combined with day and night closed loop or to sensor augmented insulin pump therapy.
- Automated day and night closed loop insulin delivery (intervention arm) combined with pump suspend feature (interventional arm): At the start, a blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. A subset of participants will be interviewed to enable their historical diabetes management practices, everyday work and family lives, and their initial expectations of using closed loop technology to be captured and explored in-depth. Subjects will be admitted to the clinical facility on Day 1. Training on the use of closed loop and pump suspend feature will be provided by the research team. During the next 2-4 hours patient will operate the system under the supervision of the clinical team. Competency on the use of closed loop system will be evaluated. Subjects will use closed loop and pump suspend feature for 12 weeks.
- Sensor augmented insulin pump therapy (control arm):
A blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. Subjects will use sensor augmented insulin pump therapy without pump suspend feature for 12 weeks.
End of study assessments:
- A blood sample will be taken for measurement of HbA1c.
- Validated questionnaires evaluating the impact of the devices employed on life change, diabetes management will be completed.
- Cognitive assessment will be made using validated computerized cognitive tests.
- Follow-up interviews will be undertaken with the subset of participants/family members at the end of the closed loop intervention.
Procedures for safety monitoring during trial:
- Standard operating procedures for monitoring and reporting of all adverse events will be in place, including serious adverse events (SAE), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia.
- Subjects will be asked to test and record blood or urine ketones if their finger prick glucose is above 14.0mmol/l (250mg/dl) in the morning on waking, as part of the safety assessment for hyperglycaemia.
- 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 patients on safety grounds:
A subject, parent, or guardian 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:
- Serious adverse events
- Significant protocol violation or non-compliance
- Failure to satisfy competency assessment
- Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
- Pregnancy, planned pregnancy, or breast feeding
- Allergic reaction to insulin
- Technical grounds (e.g. subject relocates)
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
- Being tested
- FlorenceM, Medtronic insulin pump 640G
- Keywords
- Type 1 diabetes, Closed-loop glucose control, Artificial Pancreas, Continuous subcutaneous insulin infusion, Continuous glucose monitoring, threshold suspend, predictive low glucose suspend
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlorenceMDevice
The automated closed loop system (FlorenceM) will consist of:
- Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family real time CGM and glucose suspend feature.
- An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device.
Medtronic insulin pump 640GDevice
Next generation sensor-augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family real time CGM. Glucose suspend features will be turned off.
| Study group | Role | What they receive |
|---|---|---|
| 24/7 closed loop insulin delivery | Experimental | Unsupervised home use of day and night automated closed loop insulin delivery system (FlorenceM) combined with pump suspend feature over a 12-week period using 24/7 Medtronic insulin pump 640G and Android smartphone. Receives: Device: FlorenceM |
| Sensor augmented pump therapy | Active comparator | Insulin pump therapy combined with unmasked real-time continuous glucose monitoring system for 12 weeks using Medtronic insulin pump 640G. Pump suspend features will be turned off. Receives: Device: Medtronic insulin pump 640G |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels
both arms
Measured: 12 week intervention phase
Secondary outcomes (12)
HbA1c at the end of treatment period
Between group differences in HbA1c levels at the end of treatment period adjusted for pre-study period HbA1c level.
Measured: HbA1c will be taken at the end of 12-week study intervention.
Time spent below target glucose (3.9mmol/l)(70mg/dl)
both arms
Measured: 12 week intervention phase
Time spent above target glucose (10.0 mmol/l) (180 mg/dl)
both arms
Measured: 12 week intervention phase
Average of glucose levels
both arms
Measured: 12 week intervention phase
The time with glucose levels < 3.5 mmol/l (63mg/dl) and <2.8 mmol/l (50mg/dl)
both arms
Measured: 12 week intervention phase
The time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)
both arms
Measured: 12 week intervention phase
Total, basal and bolus insulin dose
both arms
Measured: 12 week intervention phase
AUC of glucose below 3.5mmol/l (63mg/dl)
both arms
Measured: 12 week intervention phase
Standard deviation of glucose levels
both arms
Measured: 12 week intervention phase
Coefficient of variation of glucose levels
both arms
Measured: 12 week intervention phase
Number of pump suspend events
closed-loop arm only
Measured: 12 week intervention phase
Change of body weight from screening to end of study
both arms
Measured: 12 week intervention phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2015 (estimated)
- Study startMay 2016
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, Jaeb Center for Health Research, Cambridge University Hospitals NHS Foundation Trust, University College London Hospitals, The Leeds Teaching Hospitals NHS Trust, Manchester University NHS Foundation Trust, International Diabetes Center at Park Nicollet, University of Colorado, Denver, University of Edinburgh
- Responsible party
- Principal investigator, Dr Roman Hovorka, University of Cambridge
- Investigators
- Roman Hovorka, PhD, Study director, Department of Paedatrics, University of Cambridge, UKDavid B Dunger, Prof, Principal investigator, Department of Paedatrics, University of Cambridge, UKFiona Campbell, MD, Principal investigator, St James's University Hospital, Leeds, UKAmy Criego, Prof, Principal investigator, International Diabetes Center at Park Nicollet, Minneapolis, USAMark Evans, MD, Principal investigator, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UKLalantha Leelarathna, PhD, Principal investigator, Manchester Diabetes Centre, Manchester Royal Infirmary, Manchester, UKRichard Bergenstal, Prof, Principal investigator, International Diabetes Center at Park Nicollet, Minneapolis, USAViral Shah, MD, Principal investigator, Barbara Davis Center for Childhood Diabetes, Aurora, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02523131
- Sponsor's protocol ID
- APCam11
- Acronym
- APCam11
- Status last verified
- Mar 2018
- First submitted
- 9 Aug 2015
- Last updated
- 13 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hovorka R. Artificial Pancreas Project at Cambridge 2013. Diabet Med. 2015 Aug;32(8):987-92. doi: 10.1111/dme.12766. Epub 2015 Apr 15.
PubMed 25819473Leelarathna L, Dellweg S, Mader JK, Allen JM, Benesch C, Doll W, Ellmerer M, Hartnell S, Heinemann L, Kojzar H, Michalewski L, Nodale M, Thabit H, Wilinska ME, Pieber TR, Arnolds S, Evans ML, Hovorka R; AP@home Consortium. Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study. Diabetes Care. 2014 Jul;37(7):1931-7. doi: 10.2337/dc13-2911.
PubMed 24963110Thabit 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 24943065Hovorka R, Elleri D, Thabit H, Allen JM, Leelarathna L, El-Khairi R, Kumareswaran K, Caldwell K, Calhoun P, Kollman C, Murphy HR, Acerini CL, Wilinska ME, Nodale M, Dunger DB. Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial. Diabetes Care. 2014;37(5):1204-11. doi: 10.2337/dc13-2644.
PubMed 24757227Lawton J, Blackburn M, Breckenridge JP, Hallowell N, Farrington C, Rankin D. Ambassadors of hope, research pioneers and agents of change-individuals' expectations and experiences of taking part in a randomised trial of an innovative health technology: longitudinal qualitative study. Trials. 2019 May 27;20(1):289. doi: 10.1186/s13063-019-3373-9.
PubMed 31133076Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium. Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet. 2018 Oct 13;392(10155):1321-1329. doi: 10.1016/S0140-6736(18)31947-0. Epub 2018 Oct 3.
PubMed 30292578Bally L, Thabit H, Tauschmann M, Allen JM, Hartnell S, Wilinska ME, Exall J, Huegel V, Sibayan J, Borgman S, Cheng P, Blackburn M, Lawton J, Elleri D, Leelarathna L, Acerini CL, Campbell F, Shah VN, Criego A, Evans ML, Dunger DB, Kollman C, Bergenstal RM, Hovorka R. Assessing the effectiveness of a 3-month day-and-night home closed-loop control combined with pump suspend feature compared with sensor-augmented pump therapy in youths and adults with suboptimally controlled type 1 diabetes: a randomised parallel study protocol. BMJ Open. 2017 Jul 13;7(7):e016738. doi: 10.1136/bmjopen-2017-016738.
PubMed 28710224
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-centre, Randomised, Single-period, Parallel Design Study to Assess the Efficacy, Safety, Utility and Psychosocial Effect of 12 Week Day and Night Automated Closed Loop Glucose Control Combined With Pump Suspend Feature Compared to Sensor Augmented Insulin Pump Therapy in Youth and Adults With Type 1 Diabetes With Sub-optimal Glucose Control Under Free Living Conditions
- ClinicalTrials.gov ID
- NCT02523131
- Acronym / sponsor ID
- APCam11 / APCam11
- Conditions
- Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Endocrine System Diseases, Autoimmune Diseases
- Keywords
- Type 1 diabetes, Closed-loop glucose control, Artificial Pancreas, Continuous subcutaneous insulin infusion, Continuous glucose monitoring, threshold suspend, predictive low glucose suspend
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation, Jaeb Center for Health Research, Cambridge University Hospitals NHS Foundation Trust, University College London Hospitals, The Leeds Teaching Hospitals NHS Trust, Manchester University NHS Foundation Trust, International Diabetes Center at Park Nicollet, University of Colorado, Denver, University of Edinburgh
- Study start
- May 2016
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 14 Aug 2015 (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 determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy alone.
This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a three-month period of home study during which day and night glucose levels will be controlled either by a closed loop system combined with pump suspend feature (intervention group) or by sensor augmented insulin pump therapy (control group).
It is expected that up to 100 subjects, aiming for 84 randomised subjects [42 youth (6 to 21 years), and 42 adults (22 years and older)], with type 1 diabetes will be recruited through paediatric and adult outpatient diabetes clinics in each of the investigation centres. Subjects who drop out within the first four weeks of the intervention may be replaced. Participants will all be on subcutaneous insulin pump therapy and will have proven competencies both in the use of the study insulin pump and the study CGM device.
Subjects in the intervention group will receive appropriate training in the safe use of closed loop insulin delivery system and pump suspend feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in the time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels during the 12 week free living phase. Secondary outcomes are HbA1 at the end of treatment period, the time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes.
Detailed description
Purpose of the study:
To determine whether day and night automated closed loop glucose control combined with pump suspend feature will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to sensor augmented insulin pump therapy.
Study objectives:
- EFFICACY: The objective is to assess efficacy of day and night automated closed loop glucose control combined with pump suspend feature in maintaining glucose levels within the target range from 3.9 to 10.0mmol/l (70 to 180mg/dl) based on subcutaneous continuous glucose monitoring (CGM), as compared to sensor augmented insulin pump therapy.
- SAFETY: The objective is to evaluate the safety of day and night automated closed loop glucose control combined with pump suspend feature, in terms of episodes of severe hypoglycaemia and other adverse events.
- UTILITY: The objective is to determine the frequency and duration of the use of the automated closed loop system.
- PSYCHOSOCIAL: Subjects' and family members' perception in terms of life-style change, diabetes management and fear of hypoglycaemia will be assessed using validated questionnaires and semi-structured qualitative interviews. Cognitive functions will be assessed using validated computerized cognitive tests.
Study design:
An open-label, multi-centre, multi-national, randomised, single-period, parallel group study, contrasting day and night automated closed loop glucose control combined with pump suspend feature with sensor augmented insulin pump therapy
Population:
84 participants randomised (42 youth and 42 adults). Each centre will aim to recruit between 05 and 20 participants.
Maximum duration of study for a subject :
18 weeks
Recruitment:
The subjects will be recruited through the paediatric and adult diabetes outpatient clinics at each centre.
Consent:
Written consent/assent will be obtained from participants and/or guardians according to REC/IRB requirements.
Screening assessment:
Eligible participants will undergo a screening evaluation where blood samples for full blood count, renal, liver, thyroid function and anti-transglutaminase antibodies with IgA levels will be taken (if not done in the previous 3 months). Random C-peptide, glucose and HbA1c will also be measured, and a urine pregnancy test in females of child-bearing potential.
Questionnaires investigating participants' quality of life, psychosocial functioning and response to their current treatment will be distributed. Cognitive assessment will be made using validated computerized cognitive tests.
Study Training:
Training sessions on the use of study CGM, insulin pump (and closed loop system for those randomised to the intervention group) will be provided by the research team. Training session on the use of real-time CGM and on how to interpret real-time and retrospective stored data will be provided to all subjects/carers using written material.
Run-in Period:
During a 4 week run-in period, subjects will use study CGM and insulin pump. The research team will contact subject once weekly during the run-in period, and subjects will also be able to contact the research team for support and treatment optimisation as necessary. For compliance and to assess the ability of the subject to use the CGM and study pump safely, at least 12 days of CGM data need to be recorded and safe use of study insulin pump demonstrated during the last 14 days of run-in period.
Competency assessment:
Competency on the use of study insulin pump and study CGM will be evaluated using a competency assessment tool developed by the research team. Further training may be delivered as required.
Randomisation:
Eligible subjects will be randomised using randomisation software to the use of real-time CGM and pump suspend feature combined with day and night closed loop or to sensor augmented insulin pump therapy.
- Automated day and night closed loop insulin delivery (intervention arm) combined with pump suspend feature (interventional arm): At the start, a blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. A subset of participants will be interviewed to enable their historical diabetes management practices, everyday work and family lives, and their initial expectations of using closed loop technology to be captured and explored in-depth. Subjects will be admitted to the clinical facility on Day 1. Training on the use of closed loop and pump suspend feature will be provided by the research team. During the next 2-4 hours patient will operate the system under the supervision of the clinical team. Competency on the use of closed loop system will be evaluated. Subjects will use closed loop and pump suspend feature for 12 weeks.
- Sensor augmented insulin pump therapy (control arm):
A blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. Subjects will use sensor augmented insulin pump therapy without pump suspend feature for 12 weeks.
End of study assessments:
- A blood sample will be taken for measurement of HbA1c.
- Validated questionnaires evaluating the impact of the devices employed on life change, diabetes management will be completed.
- Cognitive assessment will be made using validated computerized cognitive tests.
- Follow-up interviews will be undertaken with the subset of participants/family members at the end of the closed loop intervention.
Procedures for safety monitoring during trial:
- Standard operating procedures for monitoring and reporting of all adverse events will be in place, including serious adverse events (SAE), serious adverse device effects (SADE) and specific adverse events (AE) such as severe hypoglycaemia.
- Subjects will be asked to test and record blood or urine ketones if their finger prick glucose is above 14.0mmol/l (250mg/dl) in the morning on waking, as part of the safety assessment for hyperglycaemia.
- 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 patients on safety grounds:
A subject, parent, or guardian 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:
- Serious adverse events
- Significant protocol violation or non-compliance
- Failure to satisfy competency assessment
- Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
- Pregnancy, planned pregnancy, or breast feeding
- Allergic reaction to insulin
- Technical grounds (e.g. subject relocates)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 24/7 closed loop insulin delivery | Experimental | Device: FlorenceMUnsupervised home use of day and night automated closed loop insulin delivery system (FlorenceM) combined with pump suspend feature over a 12-week period using 24/7 Medtronic insulin pump 640G and Android smartphone. |
| Sensor augmented pump therapy | Active comparator | Device: Medtronic insulin pump 640GInsulin pump therapy combined with unmasked real-time continuous glucose monitoring system for 12 weeks using Medtronic insulin pump 640G. Pump suspend features will be turned off. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- The subject is at least 6 years or older [with equal proportion of youth (6 to 21 years) and adults (22 years and older)]
- The subject has type 1 diabetes, as defined by WHO for at least 1 year or is confirmed C-peptide negative
- The subject will have been an insulin pump user for at least 3 months, with good knowledge of insulin self-adjustment as judged by the investigator
- The subject is treated with one of the rapid acting insulin analogues (insulin Aspart, Lispro or Glulisine)
- The subject is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day
Key exclusion criteria (30 listed)
- Non-type 1 diabetes mellitus including those secondary to chronic disease
- Subject using real-time CGM on regular basis in preceding 3 months
- Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- Untreated coeliac disease or thyroid disease or subject is being treated for hypothyroidism at time of screening
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
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 |
|---|---|---|
| FlorenceMThe automated closed loop system (FlorenceM) will consist of: * Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family real time CGM and glucose suspend feature. * An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device. | Device | 24/7 closed loop insulin delivery |
| Medtronic insulin pump 640GNext generation sensor-augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite 3 family real time CGM. Glucose suspend features will be turned off. | Device | Sensor augmented pump therapy |
Primary outcome
Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels
Time frame: 12 week intervention phase
both arms
12 secondary outcomes
HbA1c at the end of treatment period
Time frame: HbA1c will be taken at the end of 12-week study intervention.
Time spent below target glucose (3.9mmol/l)(70mg/dl)
Time frame: 12 week intervention phase
Time spent above target glucose (10.0 mmol/l) (180 mg/dl)
Time frame: 12 week intervention phase
Average of glucose levels
Time frame: 12 week intervention phase
The time with glucose levels < 3.5 mmol/l (63mg/dl) and <2.8 mmol/l (50mg/dl)
Time frame: 12 week intervention phase
The time with glucose levels in the significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl)
Time frame: 12 week intervention phase
Total, basal and bolus insulin dose
Time frame: 12 week intervention phase
AUC of glucose below 3.5mmol/l (63mg/dl)
Time frame: 12 week intervention phase
Standard deviation of glucose levels
Time frame: 12 week intervention phase
Coefficient of variation of glucose levels
Time frame: 12 week intervention phase
Number of pump suspend events
Time frame: 12 week intervention phase
Change of body weight from screening to end of study
Time frame: 12 week intervention phase
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 13 Mar 2018.
- Background: PubMed 25819473Hovorka R. Artificial Pancreas Project at Cambridge 2013. Diabet Med. 2015 Aug;32(8):987-92. doi: 10.1111/dme.12766. Epub 2015 Apr 15.
- Background: PubMed 24963110Leelarathna L, Dellweg S, Mader JK, Allen JM, Benesch C, Doll W, Ellmerer M, Hartnell S, Heinemann L, Kojzar H, Michalewski L, Nodale M, Thabit H, Wilinska ME, Pieber TR, Arnolds S, Evans ML, Hovorka R; AP@home Consortium. Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study. Diabetes Care. 2014 Jul;37(7):1931-7. doi: 10.2337/dc13-2911.
- Background: 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.
- Background: PubMed 24757227Hovorka R, Elleri D, Thabit H, Allen JM, Leelarathna L, El-Khairi R, Kumareswaran K, Caldwell K, Calhoun P, Kollman C, Murphy HR, Acerini CL, Wilinska ME, Nodale M, Dunger DB. Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial. Diabetes Care. 2014;37(5):1204-11. doi: 10.2337/dc13-2644.
- Derived from this study: PubMed 31133076Lawton J, Blackburn M, Breckenridge JP, Hallowell N, Farrington C, Rankin D. Ambassadors of hope, research pioneers and agents of change-individuals' expectations and experiences of taking part in a randomised trial of an innovative health technology: longitudinal qualitative study. Trials. 2019 May 27;20(1):289. doi: 10.1186/s13063-019-3373-9.
- Derived from this study: PubMed 30292578Tauschmann M, Thabit H, Bally L, Allen JM, Hartnell S, Wilinska ME, Ruan Y, Sibayan J, Kollman C, Cheng P, Beck RW, Acerini CL, Evans ML, Dunger DB, Elleri D, Campbell F, Bergenstal RM, Criego A, Shah VN, Leelarathna L, Hovorka R; APCam11 Consortium. Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial. Lancet. 2018 Oct 13;392(10155):1321-1329. doi: 10.1016/S0140-6736(18)31947-0. Epub 2018 Oct 3.
- Derived from this study: PubMed 28710224Bally L, Thabit H, Tauschmann M, Allen JM, Hartnell S, Wilinska ME, Exall J, Huegel V, Sibayan J, Borgman S, Cheng P, Blackburn M, Lawton J, Elleri D, Leelarathna L, Acerini CL, Campbell F, Shah VN, Criego A, Evans ML, Dunger DB, Kollman C, Bergenstal RM, Hovorka R. Assessing the effectiveness of a 3-month day-and-night home closed-loop control combined with pump suspend feature compared with sensor-augmented pump therapy in youths and adults with suboptimally controlled type 1 diabetes: a randomised parallel study protocol. BMJ Open. 2017 Jul 13;7(7):e016738. doi: 10.1136/bmjopen-2017-016738.
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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 study director
Department of Paedatrics, University of Cambridge, UK
David B Dunger, Prof principal investigator
Department of Paedatrics, University of Cambridge, UK
Fiona Campbell, MD principal investigator
St James's University Hospital, Leeds, UK
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FlorenceM and Medtronic insulin pump 640G in people with Diabetes Mellitus and Diabetes Mellitus, Type 1, run by University of Cambridge at 8 sites in 2 countries.
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 15 inclusion and 30 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 13 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United Kingdom, United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Time spent in the target glucose range from 3.9 to 10.0 mmol/l (70 to 180mg/dl) based on CGM glucose levels (time frame: 12 week intervention phase). 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 NCT02523131, which also lists 7 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 13 Mar 2018.