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Trial record 26 of 340 for:    C-peptide | "Diabetes Mellitus, Insulin-Dependent"

Closed Loop From Onset in Type 1 Diabetes (CLOuD)

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ClinicalTrials.gov Identifier: NCT02871089
Recruitment Status : Active, not recruiting
First Posted : August 18, 2016
Last Update Posted : November 26, 2019
Sponsor:
Collaborators:
Cambridge University Hospitals NHS Foundation Trust
Alder Hey Children's NHS Foundation Trust
Nottingham University Hospitals NHS Trust
Oxford University Hospitals NHS Trust
University Hospital Southampton NHS Foundation Trust
Jaeb Center for Health Research
The Leeds Teaching Hospitals NHS Trust
University of Edinburgh
Information provided by (Responsible Party):
Dr Roman Hovorka, University of Cambridge

Brief Summary:

The purpose of the study is to use a novel treatment approach, the artificial pancreas, after diagnosis of type 1 diabetes (T1D) to improve glucose control with the anticipated improvements of residual C-peptide secretion.

This is an open-label, multicentre, single-period, randomised, parallel group design study. It is expected that a total of up to 190 subjects (aiming for 96 randomised subjects) will be recruited within ten working days of diagnosis of type 1 diabetes through paediatric diabetes centres in the UK. Half of the participants aged 10 to 16.9 years will be treated by conventional insulin injections and the other half by the artificial pancreas (closed loop insulin delivery system). Each treatment will last 24 months. All participants completing the 24 month study period will be invited to continue in an optional extension phase with the treatment allocated at randomisation for a further 24 months.

Subjects in the intervention group will receive additional training on components of the artificial pancreas, i.e. insulin pump and continuous glucose monitoring (CGM), prior to starting closed loop insulin delivery. Subjects in the control intervention group will continue with standard therapy, i.e. multiple daily injection therapy. The study includes up to 14 visits and 1 telephone/email contact for subjects completing the study. After run-in and randomisation, visits will be conducted every 3 months in both arms. Beta-cell function will be assessed by serial measurement of C-peptide in response to a standardised mixed meal tolerance test (MMTT). MMTTs will be conducted at baseline, 6-,12- and 24 months post diagnosis.

The primary outcome is the between group difference in the area under the stimulated C-peptide curve (AUC) of the MMTT at 12 month post diagnosis. Secondary outcomes include between group differences in stimulated C-peptide AUC over 24 months, differences in glycaemic control as assessed by HbA1c, time spent in glucose target range, glucose variability, hypo- and hyperglycaemia as recorded by periodically applied CGM, as well as insulin requirements and change in bodyweight. Additionally, cognitive, emotional and behavioural characteristics of participating subjects and parents will be assessed, and a cost utility analysis on the benefits of closed loop insulin delivery will be performed. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes, diabetic ketoacidosis (DKA) and number, nature and severity of other adverse events.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus Type 1 Diabetes Device: Closed-loop system (Florence M or CamAPS FX) Other: Multiple Daily Injections Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-label, Multicentre, Randomised, Single-period, Parallel Design Study to Assess the Effect of Closed Loop Insulin Delivery From Onset of Type 1 Diabetes in Youth on Residual Beta Cell Function Compared to Standard Insulin Therapy
Actual Study Start Date : January 2017
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
Drug Information available for: Insulin

Arm Intervention/treatment
Experimental: 24/7 Closed loop delivery
Unsupervised home use of day and night automated closed-loop insulin delivery system FlorenceM (Medtronic 640G insulin pump, guardian 3 CGM and Android smartphone) of CamAPS FX (Dana insulin pump, Dexcom G6 CGM and App on Android smartphone) until 24 months after diagnosis
Device: Closed-loop system (Florence M or CamAPS FX)

The automated closed-loop system (FlorenceM) will consist of:

  • Sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Enlite/Guardian 3 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.

The automated closed-loop system (CamAPS FX) will consist of:

  • Dana R or RS insulin pump
  • Dexcom G6 real-time CGM
  • CamAPS FX App on an unlocked android smartphone.

Rapid acting insulin analogue will be used (insulin aspart, insulin lispro, insulin glulisine or similar or ultra-rapid insulin analogue).


Active Comparator: Multiple Daily Injections
Participants will apply standard insulin therapy using multiple daily injections via insulin pens during the 24 months control period
Other: Multiple Daily Injections

Rapid acting insulin analogue and long acting insulin analogue will be subcutaneously administered using CE-marked insulin pen devices in accordance with the manufacturer's instructions for their intended purposes.

Participants will be given long acting analogue (insulin glargine, insulin detemir or similar) once or twice daily according to their needs and boluses of rapid acting analogue (insulin aspart, insulin lispro, insulin glulisine or similar or ultra-rapid insulin analogue) when carbohydrates are consumed.





Primary Outcome Measures :
  1. Area under the meal stimulated C-peptide curve (AUC) during a mixed meal tolerance test (MMTT) [ Time Frame: 12 months post diagnosis ]

Secondary Outcome Measures :
  1. Mean stimulated C-peptide AUC during a mixed meal tolerance test [ Time Frame: Baseline, 6 months and 24 months post diagnosis ]
  2. HbA1c Levels [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  3. Percentage of patients in each group with HbA1c <7.5% (58mmol/mol) [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  4. Percentage of time spent with sensor glucose readings in the target range (3.9 to 10mmol/l) [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  5. Mean sensor glucose level [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  6. Standard deviation of sensor glucose levels [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  7. Coefficient of variation of sensor levels [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  8. Percentage of time with sensor glucose levels <3.5 mmol/l and <2.8 mmol/l [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  9. Percentage of time spent below target glucose (3.9mmol/l) [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  10. AUC of sensor glucose below 3.5mmol/l [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  11. Time spent with sensor glucose above target (10.0 mmol/l) [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  12. Time with sensor glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/l) [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Both arms

  13. Insulin Requirements [ Time Frame: Baseline, 3, 6, 9, 12, 15, 18, 21 and 24 months post diagnosis ]
    Total, basal and bolus insulin dose (U/kg). Both arms

  14. Weight [ Time Frame: Baseline, 6, 12 and 24 months post diagnosis ]
    Change in body mass index (BMI) standard deviation score. Both arms

  15. Blood pressure [ Time Frame: Baseline, 6, 12 and 24 months post diagnosis ]
    Both arms

  16. Lipid profile [ Time Frame: Baseline, 12 and 24 months post diagnosis ]
    Both arms


Other Outcome Measures:
  1. Severe hypoglycaemic episodes [ Time Frame: 24 month intervention period ]
    Frequency of severe hypoglycaemic episodes

  2. Diabetes ketoacidosis [ Time Frame: 24 month intervention period ]
    Frequency of severe diabetes ketoacidosis

  3. Adverse Events [ Time Frame: 24 month intervention period + 3 weeks ]
    Number, nature and severity of other adverse events. The period during which adverse events will be reported is defined as the period from the beginning of the study (obtaining informed consent) until 3 weeks after the end of the study participation

  4. Serious Adverse Events [ Time Frame: 24 month intervention period + 3 weeks ]
    Number, nature and severity of serious adverse events. The period during which adverse events will be reported is defined as the period from the beginning of the study (obtaining informed consent) until 3 weeks after the end of the study participation

  5. Assessment of the frequency of use of the closed loop system [ Time Frame: 24 month intervention period ]
    Utility evaluation

  6. Assessment of the duration of use of the closed loop system. [ Time Frame: 24 month intervention period ]
    Utility evaluation

  7. Cognitive Assessment [ Time Frame: Baseline, 6, 12 and 24 months post diagnosis ]
    Assessment of cognitive changes using computerized cognitive testing.

  8. Health Economic Evaluation [ Time Frame: 24 month intervention period ]
    Cost utility analysis using the CORE Diabetes Model (CDM; IMS Health, Basel, Switzerland) on the benefits of closed loop insulin delivery to inform reimbursement decision-making.

  9. Quantitative Human Factor Assessment [ Time Frame: Baseline,12 and 24 months post diagnosis ]
    Questionnaires will be completed by participants and parents/guardians.

  10. Qualitative Human Factor Assessment [ Time Frame: 12 and 24 months post diagnosis ]
    Interview and focus group with participants and parents/guardians.



Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of type 1 diabetes within previous 21 days. Day 1 will be defined as the day insulin was first administered. Type 1 diabetes will be defined according to WHO criteria using standard diagnostic practice.

    [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.).']

  2. The subject is at least 10 years and not older than 16.9 years
  3. The subject/carer is willing to perform regular capillary blood glucose monitoring, with at least 4 blood glucose measurements taken every day
  4. The subject is literate in English
  5. The subject is willing to wear glucose sensor
  6. The subject is willing to wear closed loop system at home
  7. The subject is willing to follow study specific instructions
  8. The subject is willing to upload pump and CGM data at regular intervals

Exclusion Criteria:

  1. Physical or psychological condition likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
  2. Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
  3. Known or suspected allergy to insulin
  4. Regular use of acetaminophen
  5. Lack of reliable telephone facility for contact
  6. Pregnancy, planned pregnancy, or breast feeding
  7. Living alone
  8. Severe visual impairment
  9. Severe hearing impairment
  10. Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
  11. 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
  12. Illicit drugs abuse
  13. Prescription drugs abuse
  14. Alcohol abuse
  15. Sickle cell disease, haemoglobinopathy, receiving red blood cell transfusion or erythropoietin within 3 months prior to time of screening
  16. Eating disorder such as anorexia or bulimia
  17. Milk protein allergy

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): NCT02871089


Locations
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United Kingdom
Southampton Children's Hospital
Southampton, Hampshire, United Kingdom, SO16 6YD
Nottingham Children's Hospital
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
John Radcliffe Hospital
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Alder Hey Children's NHS Foundation Trust
Liverpool, West Derby, United Kingdom, L12 2AP
St James's University Hospital
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom, CB2 0QQ
Royal Hospital for Sick Children
Edinburgh, United Kingdom, EH9 1LF
Sponsors and Collaborators
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
Alder Hey Children's NHS Foundation Trust
Nottingham University Hospitals NHS Trust
Oxford University Hospitals NHS Trust
University Hospital Southampton NHS Foundation Trust
Jaeb Center for Health Research
The Leeds Teaching Hospitals NHS Trust
University of Edinburgh
Investigators
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Study Director: Roman Hovorka, PhD Department of Paediatrics, University of Cambridge, UK
Principal Investigator: Ajay Thankamony, MD Department of Paediatrics, University of Cambridge, UK
Principal Investigator: Atrayee Ghatak, MD Alder Hey Children's NHS Foundation Trust, Liverpool
Principal Investigator: Tabitha Randell, MD Nottingham Children's Hospital, Nottingham, UK
Principal Investigator: Rachel Besser, MD Oxford Children's Hospital, Oxford, UK
Principal Investigator: Nicola Trevelyan, MD Southampton Children's Hospital, Southampton, UK
Principal Investigator: Daniela Elleri, MD Royal Hospital for Sick Children, Edinburgh, UK
Principal Investigator: Fiona Campbell, MD Leeds Children's Hospital

Publications:
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Responsible Party: Dr Roman Hovorka, Director of Research, University of Cambridge
ClinicalTrials.gov Identifier: NCT02871089     History of Changes
Other Study ID Numbers: CLOuD
First Posted: August 18, 2016    Key Record Dates
Last Update Posted: November 26, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Dr Roman Hovorka, University of Cambridge:
Type 1 Diabetes
Closed-loop glucose control
Artificial Pancreas
Continuous subcutaneous insulin infusion
Multiple daily injection therapy
New onset type 1 diabetes
Residual C-Peptide secretion
Beta-cell function preservation
Continuous glucose monitoring
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs