Closing the Loop in Adults With Sub-optimally Controlled Type 1 Diabetes Under Free Living Conditions

NCT01961622 | Completed DMC

• 1 other identifier: AP@home04
• Study Type: interventional
• Target: 33
• Locations: 3 countries
• Sites: 3

Brief Summary

The main objective of this study is to determine whether day and night closed-loop insulin delivery for 12 weeks under free living conditions is superior to addition of real-time continuous glucose monitoring in adults with type 1 diabetes and sub-optimal glucose control on insulin pump therapy. This is an open-label, multi centre, randomised, crossover design study, involving a 6 to 8 week run-in period, during which glucose control will be optimised by a professional pump educator, followed by two 3 months study periods during which glucose levels will be controlled either by an automated closed-loop system or by subjects usual insulin pump therapy augmented with real-time continuous glucose monitoring in random order. A total of up to 42 adults (aiming for 30 completed subjects) aged 18 years and older with T1D on insulin pump therapy will be recruited through diabetes clinics and other established methods in participating centres. Subjects who drop out of the study within the first 6 weeks of the first intervention arm will be replaced. Subjects will receive appropriate training in the safe use of closed-loop insulin delivery system. Subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. Subjects will be discouraged from international travel during the first two weeks of closed-loop use. The primary outcome is time spent in target range between 3.9 and 10.0 mmol/L as recorded by CGM (adjusted for potential over-estimation) during home stay. Secondary outcomes are the HbA1c, time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Closed loop insulin delivery; Continuous subcutaneous glucose monitoring; Continuous subcutaneous insulin infusion

Outcome Measures

Primary Outcomes (1)

• Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring

  Time spent in the target glucose range from 3.9 to 10.0 mmol/l based on subcutaneous glucose monitoring (CGM) during the 90 days of home stay. Intention to treat basis.

  90 days

Secondary Outcomes (15)

• HbA1c

  90 days

• Insulin dose

  90 days

• Adverse Events

  10 months

• Utility Evaluation

  90 days

• Continuous subcutaneous glucose monitoring (CGM) based outcome

  90 days

Other Outcomes (3)

• Accuracy of CGM

  90 days

• Per Protocol Analysis

  90 days

• Effect of study intervention based on pre-study glycaemic control

  90 days

Study Arms (2)

Florence D2A Closed Loop Glucose control

EXPERIMENTAL

Subjects glucose levels are controlled by Florence D2A or similar closed loop insulin delivery system

Device: Florence D2A or similar closed loop glucose control system

CSII with real-time CGM

ACTIVE COMPARATOR

Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (FreeStyle Navigator CGM)

Device: CSII with real-time CGM

Interventions

Florence D2A or similar closed loop glucose control system DEVICE

Subject's glucose level will be controlled by the Florence D2A or similar automated closed loop glucose control system. The system comprises of FreeStyle Navigator 2 ® Continuous Glucose Monitoring (CGM) System (Abbott Diabetes Care, Alameda, CA, USA), Dana R Diabecare subcutaneous insulin infusion pump (Sooil Corp. Seoul, South Korea)or similar insulin pump, and MPC-based glucose control algorithm running on a smartphone

Florence D2A Closed Loop Glucose control

CSII with real-time CGM DEVICE

Subject glucose level controlled by usual insulin pump therapy in conjunction with real time continuous glucose monitoring (CGM)

CSII with real-time CGM

Eligibility Criteria

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

You may qualify if:

• The subject has type 1 diabetes as defined by WHO
• The subject is 18 years of age or older
• The subject will have been on an insulin pump for at least 6 months with good knowledge of insulin self-adjustment including carbohydrate counting
• The subject is treated with one of the rapid acting insulin analogues (Insulin Aspart, Insulin Lispro or Insulin Glulisine)
• HbA1c ≥7.5% (58mmol/mmol) and ≤ 10% (86 mmol/mmol) based on analysis from central laboratory or equivalent
• The subject is willing to perform regular finger-prick blood glucose monitoring, with at least 6 measurements per day
• The subject is willing to wear closed-loop system at home and at work place
• The subject is willing to follow study specific instructions
• The subject is willing to upload pump and CGM data at regular intervals
• Female subjects of child bearing age should be on effective contraception and must have a negative urine-HCG pregnancy test at screening. In addition in Germany, women of childbearing potential must use a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e. less than 1% per year) and must use two independent methods of contraception, e.g. diaphragm and spermicide-coated condom.

You may not qualify if:

• Non-type 1 diabetes mellitus
• Any other physical or psychological disease or condition likely to interfere with the normal conduct of the study and interpretation of the study results
• Current treatment with drugs known to have significant interference with glucose metabolism, such as systemic corticosteroids, as judged by the investigator
• Known or suspected allergy against insulin
• Subjects with clinically significant nephropathy, neuropathy or proliferative retinopathy as judged by the investigator
• Significantly reduced hypoglycaemia awareness as judged by the investigator
• More than one episode of severe hypoglycaemia as defined by American Diabetes Association (31) in preceding 6 months (Severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions).
• Random C-peptide \> 100pmol/l with concomitant plasma glucose \>4 mM(72 mg/dl)
• Total daily insulin dose \> 2 IU/kg/day
• Subject is pregnant or breast feeding or planning pregnancy in near future (within next 3 months)
• Severe visual impairment
• Severe hearing impairment
• Subjects using implanted internal pacemaker
• Lack of reliable telephone facility for contact
• Subject not proficient in English (UK) or German (Germany and Austria)

Sponsors & Collaborators

• University of Cambridge: lead
• Profil Institut für Stoffwechselforschung GmbH: collaborator
• Medical University of Graz: collaborator

Study Sites (3)

Medical University of Graz

Graz, A8036, Austria

Location

Profil Institut für Stoffwechselforschung GmbH

Neuss, D41460, Germany

Location

University of Cambridge

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (5)

• Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.

  PMID: 20138357 BACKGROUND

• Hovorka R, Kumareswaran K, Harris J, Allen JM, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011 Apr 13;342:d1855. doi: 10.1136/bmj.d1855.

  PMID: 21493665 BACKGROUND

• Hovorka R. Closed-loop insulin delivery: from bench to clinical practice. Nat Rev Endocrinol. 2011 Feb 22;7(7):385-95. doi: 10.1038/nrendo.2011.32.

  PMID: 21343892 BACKGROUND

• Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartnell S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hindmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R. Home Use of an Artificial Beta Cell in Type 1 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2129-2140. doi: 10.1056/NEJMoa1509351. Epub 2015 Sep 17.

  PMID: 26379095 DERIVED

• Leelarathna L, Dellweg S, Mader JK, Barnard K, Benesch C, Ellmerer M, Heinemann L, Kojzar H, Thabit H, Wilinska ME, Wysocki T, Pieber TR, Arnolds S, Evans ML, Hovorka R; AP@home consortium. Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol. BMJ Open. 2014 Sep 3;4(9):e006075. doi: 10.1136/bmjopen-2014-006075.

  PMID: 25186158 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Roman Hovorka, PhD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 30, 2013
• First Posted: October 11, 2013
• Study Start: April 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

GB (1); AU (1); DE (1)