Home Testing of Day and Night Closed Loop With Pump Suspend Feature

NCT02523131 | Completed DMC

• 1 other identifier: APCam11
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 8

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  12 week intervention phase

Secondary Outcomes (12)

• HbA1c at the end of treatment period

  HbA1c will be taken at the end of 12-week study intervention.

• Time spent below target glucose (3.9mmol/l)(70mg/dl)

  12 week intervention phase

• Time spent above target glucose (10.0 mmol/l) (180 mg/dl)

  12 week intervention phase

• Average of glucose levels

  12 week intervention phase

• The time with glucose levels < 3.5 mmol/l (63mg/dl) and <2.8 mmol/l (50mg/dl)

  12 week intervention phase

Other Outcomes (7)

• Number of episodes of severe hypoglycaemia per subject and incidence rate per 100-person years

  12 week intervention phase

• Number of subjects with severe hypoglycemia events

  12 week intervention phase

• Number of subjects with severe hyperglycemia events as defined by fingerprick glucose >16.7 mmol/l (>300 mg/dl) and plasma ketones >0.6 mmol/l

  12 week intervention phase

Study Arms (2)

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.

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.

Device: Medtronic insulin pump 640G

Interventions

FlorenceM DEVICE

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.

24/7 closed loop insulin delivery

Medtronic insulin pump 640G DEVICE

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.

Sensor augmented pump therapy

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[with equal proportion of subjects above and below HbA1c 8.5% (69mmol/mol)\]
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Cambridge: lead
• Juvenile Diabetes Research Foundation: collaborator
• Jaeb Center for Health Research: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• University College London Hospitals: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• Manchester University NHS Foundation Trust: collaborator
• International Diabetes Center at Park Nicollet: collaborator
• University of Colorado, Denver: collaborator
• University of Edinburgh: collaborator

Study Sites (8)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

International Diabetes Center at Park Nicollet

Minneapolis, Minnesota, 55416, United States

Location

International Diabetes Centre at Park Nicollet

Minneapolis, Minnesota, 55416, United States

Location

University of Cambridge

Cambridge, CB2 0QQ, United Kingdom

Location

Wellcome Trust-MRC Institute of Metabolic Science

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Hospital for Sick Children

Edinburgh, EH9 1LF, United Kingdom

Location

Leeds Teaching Hospitals

Leeds, LS9 7TF, United Kingdom

Location

Manchester Diabetes Centre, Manchester Royal Infirmary

Manchester, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 25819473 BACKGROUND

• Leelarathna 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.

  PMID: 24963110 BACKGROUND

• Thabit 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.

  PMID: 24943065 BACKGROUND

• Hovorka 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.

  PMID: 24757227 BACKGROUND

• Lawton 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.

  PMID: 31133076 DERIVED

• Tauschmann 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.

  PMID: 30292578 DERIVED

• Bally 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.

  PMID: 28710224 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Immune System Diseases

Study Officials

• Roman Hovorka, PhD

  Department of Paedatrics, University of Cambridge, UK

  STUDY DIRECTOR

• David B Dunger, Prof

  Department of Paedatrics, University of Cambridge, UK

  PRINCIPAL INVESTIGATOR

• Fiona Campbell, MD

  St James's University Hospital, Leeds, UK

  PRINCIPAL INVESTIGATOR

• Amy Criego, Prof

  International Diabetes Center at Park Nicollet, Minneapolis, USA

  PRINCIPAL INVESTIGATOR

• Mark Evans, MD

  Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK

  PRINCIPAL INVESTIGATOR

• Lalantha Leelarathna, PhD

  Manchester Diabetes Centre, Manchester Royal Infirmary, Manchester, UK

  PRINCIPAL INVESTIGATOR

• Richard Bergenstal, Prof

  International Diabetes Center at Park Nicollet, Minneapolis, USA

  PRINCIPAL INVESTIGATOR

• Viral Shah, MD

  Barbara Davis Center for Childhood Diabetes, Aurora, USA

  PRINCIPAL INVESTIGATOR

• Daniela Elleri, MD

  Endocrine/Diabetes Department, Royal Hospital for Sick Children, Edinburgh, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: August 9, 2015
• First Posted: August 14, 2015
• Study Start: May 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 13, 2018

Record last verified: 2018-03

Locations

GB (5); US (3)