Day and Night Closed-loop in Young People With Type 1 Diabetes

NCT02925299 | Completed DMC FDA Device

• 2 other identifiers: DAN051UC4DK108520-01
• Study Type: interventional
• Target: 131
• Locations: 2 countries
• Sites: 11

Brief Summary

The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c. This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 6 month period of home study during which day and night glucose levels will be controlled either by a closed-loop system combined with low glucose feature (intervention group) or by insulin pump therapy alone (control group). It is expected that a total of up to 150 subjects (aiming for 130 randomised subjects) with type 1 diabetes will be recruited through paediatric outpatient diabetes clinics of the investigation centres. Participants will all be on subcutaneous insulin pump therapy. Subjects in the intervention group will have proven competencies both in the use of the study insulin pump and the study continuous glucose monitoring (CGM) device, and will receive appropriate training in the safe use of closed-loop insulin delivery system and low glucose 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 HbA1c levels at 6 months post study arm initiation. Secondary outcomes are the time spent in the glucose target (3.9 to 10.0mmol/l; 70 to 180mg/dl), 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 and diabetic ketoacidosis (DKA).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• The primary outcome is the centralised measurement of glycated haemoglobin (HbA1c) at 6 months.

  The objective is to assess efficacy of day and night automated closed-loop glucose control combined with low glucose feature in improving HbA1c, as compared with insulin pump therapy alone.

  HbA1c will be taken at baseline, 3 and 6 months

Secondary Outcomes (12)

• Time spent in the target glucose range (3.9 to 10mmol/l) (70 to 180mg/dl)

  6 months

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

  6 months

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

  6 months

• Mean and standard deviation or percentiles sensor glucose

  6 months

• Coefficient of variation of glucose levels

  6 months

Other Outcomes (4)

• Safety Evaluation

  6 months

• Utility evaluation

  6 months

• Human Factors Assessment

  6 months

Study Arms (2)

24/7 closed loop insulin delivery

EXPERIMENTAL

The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed, and (3) an insulin pump that delivers the insulin. The name of this closed-loop system used in the US is FlorenceM (Medtronic 640G pump and Guardian3 sensor). The name of this closed-loop system in the UK is FlorenceX (DANA pump and Dexcom sensor). Half of the individuals taking part in the study will use the closed-loop study system for 6 months.

Device: FlorenceM (US) and FlorenceX (UK)

Insulin pump therapy

ACTIVE COMPARATOR

Half of the Subjects will continue using their own insulin pump for 6 months.

Device: Insulin pump therapy

Interventions

FlorenceM (US) and FlorenceX (UK) DEVICE

The automated closed loop system (FlorenceM in US) will consist of: Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Guardian3 CGM and glucose suspend feature. The automated closed loop system (FlorenceX in UK) will consist of: The DANA Diabecare R insulin pump (Sooil Development, Korea) incorporating the Dexcom G6 CGM. 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

Insulin pump therapy DEVICE

Subjects will continue using their own insulin pump for 6 months.

Insulin pump therapy

Eligibility Criteria

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

You may qualify if:

• Age ≥6 and \<19 years
• Type 1 diabetes as defined by WHO (51) for at least 1 year \[WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).'\]
• Use of an insulin pump for at least 3 months, with good knowledge of insulin self-adjustment by subject or caregiver as judged by the investigator
• Using U-100 rapid acting insulin analogues insulin Aspart or Lispro only
• Willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements per day day
• Screening HbA1c ≥ 7.0% (53 mmol/mol) and ≤10 % (86mmol/mol) based on analysis from local laboratory
• Literate in English
• Willing to wear glucose sensor
• Willing to wear closed-loop system at home
• Willing to follow study specific instructions
• Willing to upload pump and CGM data at regular intervals
• Access to WiFi.
• Lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance

You may not qualify if:

• Living alone
• Current use of any closed-loop system
• 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, adrenal insufficiency, or untreated thyroid disease
• 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
• 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
• Recurrent incidents of severe hypoglycaemia (\>1 episode) during the previous 6 months (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)
• Recurrent incidents of diabetic ketoacidosis (\>1 episode) during previous 6 months
• Unwilling to avoid 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

• Jaeb Center for Health Research: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• University of Colorado, Denver: collaborator
• Indiana University: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• Stanford University: collaborator
• Yale University: collaborator
• Nemours Children's Health System: collaborator

Study Sites (11)

Stanford University

Palo Alto, California, 95032, United States

Location

University of Colorado Denver School of Medicine Barbara Davis Center

Aurora, Colorado, 80045, United States

Location

Yale University

Hartford, Connecticut, 06520, United States

Location

Nemours Children's Health System

Jacksonville, Florida, 32207, United States

Location

Indiana University

Indianapolis, Indiana, 43202, United States

Location

University of Cambridge

Cambridge, Cambridgeshire County, CB2 0QQ, United Kingdom

Location

Nottingham Children's Hospital

Nottingham, England, NG5 1PB, United Kingdom

Location

Southampton Children's Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, United Kingdom

Location

Oxford Children's Hospital

Oxford, United Kingdom

Location

Related Publications (2)

• Ware J, Boughton CK, Allen JM, Wilinska ME, Tauschmann M, Denvir L, Thankamony A, Campbell FM, Wadwa RP, Buckingham BA, Davis N, DiMeglio LA, Mauras N, Besser REJ, Ghatak A, Weinzimer SA, Hood KK, Fox DS, Kanapka L, Kollman C, Sibayan J, Beck RW, Hovorka R; DAN05 Consortium. Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial. Lancet Digit Health. 2022 Apr;4(4):e245-e255. doi: 10.1016/S2589-7500(22)00020-6. Epub 2022 Mar 7.

  PMID: 35272971 DERIVED

• Musolino G, Allen JM, Hartnell S, Wilinska ME, Tauschmann M, Boughton C, Campbell F, Denvir L, Trevelyan N, Wadwa P, DiMeglio L, Buckingham BA, Weinzimer S, Acerini CL, Hood K, Fox S, Kollman C, Sibayan J, Borgman S, Cheng P, Hovorka R. Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, multicentre, multinational, single-period, randomised, parallel group study protocol. BMJ Open. 2019 Jun 3;9(6):e027856. doi: 10.1136/bmjopen-2018-027856.

  PMID: 31164368 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

  University of Cambridge

  STUDY CHAIR

• Ajay Thankamony, MD

  University of Cambridge

  PRINCIPAL INVESTIGATOR

• Fiona Campbell, MD

  The Leeds Teaching Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

• Bruce Buckingham, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Stuart Weinzimer, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Linda DiMeglio, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Paul Wadwa, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Korey Hood, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Dana Goldman, PhD

  University of Southern California

  PRINCIPAL INVESTIGATOR

• Nikki C Davis, MD

  Southampton Children's Hospital

  PRINCIPAL INVESTIGATOR

• Louise Denvir, MD

  Nottingham Children's Hospital

  PRINCIPAL INVESTIGATOR

• Nelly Mauras, MD

  Nemours Children's Health System

  PRINCIPAL INVESTIGATOR

• Rachel Besser, MD

  Oxford Children's Hospital

  PRINCIPAL INVESTIGATOR

• Atrayee Ghatak, MD

  Alder Hey Children's NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2016
• First Posted: October 5, 2016
• Study Start: May 12, 2017
• Primary Completion: August 27, 2020
• Study Completion: August 27, 2020
• Last Updated: February 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); GB (6)