Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Day and Night Closed-loop in Young People With Type 1 Diabetes (DAN05)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02925299
Recruitment Status : Recruiting
First Posted : October 5, 2016
Last Update Posted : October 3, 2019
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Cambridge University Hospitals NHS Foundation Trust
University of Colorado Denver School of Medicine Barbara Davis Center
Indiana University
The Leeds Teaching Hospitals NHS Trust
Stanford University
Yale University
Nemours Children's Health System
Information provided by (Responsible Party):
Jaeb Center for Health Research

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).


Condition or disease Intervention/treatment Phase
Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Endocrine System Diseases Autoimmune Diseases Device: FlorenceM (US) and FlorenceX (UK) Device: Insulin pump therapy Not Applicable

  Hide Detailed Description

Detailed Description:
  • Purpose of the study: To determine whether 24/7 automated closed-loop glucose control will improve glucose control as measured by glycated haemoglobin and reduce the burden of hypoglycaemia compared to insulin pump therapy alone.
  • Study Objectives:

    1. EFFICACY: The objective is to assess efficacy of day and night automated closed-loop glucose control in improving glucose control as measured by glycated haemoglobin, as compared to insulin pump therapy alone.
    2. SAFETY: The objective is to evaluate the safety of day and night automated closed-loop glucose control, in terms of episodes of severe hypoglycaemia and other adverse events.
    3. UTILITY: The objective is to determine the frequency and duration of the use of the automated closed-loop system.
    4. HUMAN FACTORS: The objective is to assess cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial using validated surveys and focus groups.
    5. HEALTH ECONOMICS: The objective is to perform a cost utility analysis to inform reimbursement decision-making.
  • Study Design: An open-label, multi-centre, randomised, single-period parallel study, contrasting day-and-night automated closed-loop glucose control with insulin pump therapy alone.
  • Population: 130 participants randomised (equal proportion of those aged 6 to 12 years and 13 to 18 years, a minimum quota of 25% participants with baseline HbA1c >8.5%)
  • Maximum duration of study for a subject: 8 months
  • Recruitment: The subjects will be recruited through the pediatric outpatient clinics at each center.
  • Consent: Written consent / assent will be obtained from participants and/or guardians according to REC / IRB requirements
  • Screening Assessments: Eligible participants will undergo a screening evaluation where blood samples for full blood count, liver, thyroid function and anti-transglutaminase antibodies (with IgA levels if not done within previous 12 months) will be taken. Non-hypoglycaemia C-peptide, glucose and HbA1c will also be measured, and a urine pregnancy test in females of child-bearing potential will be performed.

Surveys investigating participants' quality of life, psychosocial and cognitive functioning, and response to their current treatment will be distributed.

Participants will be fitted with a blinded continuous glucose monitoring (CGM) device to assess baseline glycaemic control. Instructions on how to safely use, remove and send back the device will be provided.

  • Study Training: Training sessions on the use of study CGM, insulin pump (and closed loop system for those randomized to be 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 1-2 week run-in period, subjects will continue using their own insulin pump. Data obtained from blinded CGM and pump downloads may be utilised for therapy adjustment.
  • 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.
  • Randomization: Eligible subjects will be randomised using randomisation software to the use of real-time CGM and low glucose feature combined with day and night closed-loop or to conventional insulin pump therapy alone.

A blood sample will be taken for the measurement of HbA1c and a urine pregnancy test in females of child-bearing potential. A blood sample for centralised analysis of HbA1c will be taken if screening and randomisation are >28 days apart.

  1. Automated day and night closed-loop insulin delivery (intervention arm) combined with low glucose feature (interventional arm) - Participants in the closed-loop group will receive additional training sessions following randomisation covering the use of the study insulin pump and real-time CGM, prior to starting closed-loop insulin delivery.

    Once confident with the use of the study pump and CGM system, participants will receive training required for safe and effective use of the closed-loop system approximately 2-4 weeks after randomisation. During this 2-4 hour session participants will operate the system under the supervision of the clinical team. Competency on the use of closed-loop system will be evaluated.

    Thereafter, participants are expected to use closed-loop for 6 months without direct real-time remote monitoring.

  2. Insulin pump therapy (control arm) - Refresher training on key aspects of insulin pump therapy will be provided.

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

  • 3-month and 6 month assessments:

    1. A blood sample will be taken for measurement of HbA1c and a urine pregnancy test in females of child-bearing potential.
    2. Validated surveys evaluating the impact of the devices employed on quality of life, psychosocial and cognitive functioning, diabetes management and treatment satisfaction will be completed.
    3. Participants of both study arms will be fitted with blinded CGM systems at the end of each follow up visit. The sensors will be worn at home for up to 14 days and will be sent back to the research team.

    6 months only: Subjects/guardians will be invited to join follow-up focus groups to gather feedback and reactions to their current treatment (closed-loop or insulin pump), the clinical trial, and quality of life changes.

  • Study Contacts: In between study visits, participants will be contacted by the study team (email or phone) once monthly in order to record any adverse events, device deficiencies, and changes in insulin settings, other medical conditions and/or medication.

In case of any technical device or problems related to diabetes management such as hypo- or hyperglycaemia, subjects will be able to contact a 24-hour telephone helpline to the local research team at any time. The local research team will have access to central 24 hour advice on technical issues.

--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 ketones if their finger prick glucose is > 16.7mmol/l (300mg/dl) upon awakening, >300 for more than 1 hour, or >22.2mmo/l (400mg/dL) at any time as part of the safety assessment for DKA.

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 closed-loop intervention after consideration of the benefit/risk ratio. Possible reasons are:

  1. Serious adverse events
  2. Significant protocol violation or non-compliance
  3. Failure to satisfy competency assessment
  4. Decision by the investigator, or the sponsor, that termination is in the subject's best medical interest
  5. Pregnancy, planned pregnancy, or breast feeding
  6. Allergic reaction to insulin

Efforts will be made to retain subjects in follow up for the final primary outcome assessment even if the intervention is discontinued, unless the investigator believes that it will be harmful for the subject to continue in the trial.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-centre, Randomized, Single-period, Parallel Study to Assess the Efficacy, Safety and Utility of 6 Month Day-and-night Automated Closed-loop Insulin Delivery Under Free Living Conditions Compared to Insulin Pump Therapy in Children and Adolescents With Type 1 Diabetes
Actual Study Start Date : May 12, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: 24/7 closed loop insulin delivery
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)

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.


Active Comparator: Insulin pump therapy
Half of the Subjects will continue using their own insulin pump for 6 months.
Device: Insulin pump therapy
Subjects will continue using their own insulin pump for 6 months.




Primary Outcome Measures :
  1. The primary outcome is the centralised measurement of glycated haemoglobin (HbA1c) at 6 months. [ Time Frame: HbA1c will be taken at baseline, 3 and 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.


Secondary Outcome Measures :
  1. Time spent in the target glucose range (3.9 to 10mmol/l) (70 to 180mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  2. Time spent below target glucose (3.9mmol/l)(70mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  3. Time spent above target glucose (10.0 mmol/l) (180 mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  4. Mean and standard deviation or percentiles sensor glucose [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  5. Coefficient of variation of glucose levels [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  6. Time with glucose levels < 3.5 mmol/l (63 mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  7. Time with glucose levels <3.0 mmol/l (54 mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  8. Time with glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  9. Changes in total basal and bolus insulin dose [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on CRF and insulin pump data.

  10. AUC of glucose below 3.5mmol/l (63mg/dl) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  11. AUC glucose above 10.0mmol/L (180mg/dL) [ Time Frame: 6 months ]
    Secondary endpoints regarding glucose levels will be based on sensor glucose data.

  12. HbA1c <7.0%, HbA1c <7.5%, Relative reduction ≥10% from baseline. o Absolute reduction ≥0.5% from baseline o Absolute reduction ≥1% from baseline o Absolute reduction ≥1% from baseline or HbA1c <7.0% [ Time Frame: 6 months ]
    Binary metrics for HbA1c


Other Outcome Measures:
  1. Safety Evaluation [ Time Frame: 6 months ]
    Frequency of severe hypoglycaemic episodes as defined by American Diabetes Association (adolescents), and International Society for Pediatric and Adolescent Diabetes (children), frequency of diabetic ketoacidosis (DKA), frequency of severe hyperglycaemia (>16.7 mmol/l)(>300mg/dl) with significant ketosis (plasma ketones >0.6mmol/l) and nature and severity of other adverse events

  2. Utility evaluation [ Time Frame: 6 months ]
    Assessment of the frequency and duration of use of the closed-loop system

  3. Human Factors Assessment [ Time Frame: 6 months ]
    Cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial will be assessed gathering both quantitative (validated surveys) and qualitative data (focus groups)

  4. Health Economic Evaluation [ Time Frame: 6 months ]
    Cost utility analysis on the benefits of closed loop insulin delivery to inform reimbursement decision-making



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥6 and <19 years
  2. 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.).']
  3. 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
  4. Using U-100 rapid acting insulin analogues insulin Aspart or Lispro only
  5. Willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements per day day
  6. Screening HbA1c ≥ 7.0% (53 mmol/mol) and ≤10 % (86mmol/mol) based on analysis from local laboratory
  7. Literate in English
  8. Willing to wear glucose sensor
  9. Willing to wear closed-loop system at home
  10. Willing to follow study specific instructions
  11. Willing to upload pump and CGM data at regular intervals
  12. Access to WiFi.
  13. Lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance

Exclusion Criteria:

  1. Living alone
  2. Current use of any closed-loop system
  3. 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
  4. Untreated coeliac disease, adrenal insufficiency, or untreated thyroid disease
  5. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
  6. Known or suspected allergy to insulin
  7. 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
  8. 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)
  9. Recurrent incidents of diabetic ketoacidosis (>1 episode) during previous 6 months
  10. Unwilling to avoid regular use of acetaminophen
  11. Lack of reliable telephone facility for contact
  12. Total daily insulin dose ≥ 2 IU/kg/day
  13. Total daily insulin dose < 15 IU/day
  14. Pregnancy, planned pregnancy, or breast feeding
  15. Severe visual impairment
  16. Severe hearing impairment
  17. Seizure disorder
  18. Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
  19. 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)
  20. Illicit drugs abuse
  21. Subject is currently abusing prescription drugs
  22. Alcohol abuse
  23. Use of pramlintide (Symlin), or other non-insulin glucose lowering agents including sulphonylureas, biguanides, DPP4-Inhibitors, , GLP-1 analogues, SGLT-1/ 2 inhibitors at time of screening
  24. Shift work with working hours between 10pm and 8am
  25. Sickle cell disease, haemoglobinopathy, or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
  26. Eating disorder such as anorexia or bulimia
  27. Employed by Medtronic Diabetes or with immediate family members employed by Medtronic Diabetes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02925299


Contacts
Layout table for location contacts
Contact: Roman Hovorka, PhD +44 1223 762 862 rh347@cam.ac.uk
Contact: Judy Sibayan, MPH, CCRP 813-975-8690 jsibayan@jaeb.org

Locations
Layout table for location information
United States, California
Stanford University Active, not recruiting
Palo Alto, California, United States, 95032
United States, Colorado
University of Colorado Denver School of Medicine Barbara Davis Center Active, not recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University Active, not recruiting
Hartford, Connecticut, United States, 06520
United States, Florida
Nemours Children's Health System Active, not recruiting
Jacksonville, Florida, United States, 32207
United States, Indiana
Indiana University Active, not recruiting
Indianapolis, Indiana, United States, 43202
United Kingdom
University of Cambridge Recruiting
Cambridge, Cambridgeshire County, United Kingdom, CB2 0QQ
Contact: Charlotte Boughton, MD    +44 1229 769066    cb2000@medschl.cam.ac.uk   
Contact: Janet Allen, RN    44 1223 769064    ja305@medschl.cam.au.uk   
Principal Investigator: Carlo Acerini, MD         
Nottingham Children's Hospital Recruiting
Nottingham, England, United Kingdom, NG5 1PB
Contact: Louise Denvir, MD    44 115 924 9924 ext 62336    Louise.denvir@nuh.nhs.uk   
Contact: Maria Saxton    0115 924 9924 ext 70680    Maria.Saxton@nuh.nhs.uk   
Southampton Children's Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Nikki Davis, MD       nikki.davis@uhs.nhs.uk   
Contact: Helen Dewar    023 8120 4989    Helen.Dewar@uhs.nhs.net   
The Leeds Teaching Hospitals NHS Trust Recruiting
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Contact: Fiona Campbell, MD    01132-064-996      
Contact: Emily Metcalfe    0113 206 4996 ext 64996    emily.metcalfe@nhs.net   
Sponsors and Collaborators
Jaeb Center for Health Research
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Cambridge University Hospitals NHS Foundation Trust
University of Colorado Denver School of Medicine Barbara Davis Center
Indiana University
The Leeds Teaching Hospitals NHS Trust
Stanford University
Yale University
Nemours Children's Health System
Investigators
Layout table for investigator information
Study Chair: Roman Hovorka, PhD University of Cambridge
Principal Investigator: Carlo Acerini, 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 School of Medicine Barbara Davis Center
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT02925299     History of Changes
Other Study ID Numbers: DAN05
1UC4DK108520-01 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2016    Key Record Dates
Last Update Posted: October 3, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Metabolic Diseases
Glucose Metabolism Disorders
Autoimmune Diseases
Endocrine System Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs