For type-1 diabetes, the aim of insulin therapy is to keep blood glucose close to normal while avoiding hypoglycaemia but this is severely limited by the relative crudeness of current insulin delivery in comparison with the physiology of the β-cells which secrete insulin. Insulin is generally administered by multiple injections MDI with the dose adjusted according to eating and exercise. Insulin can now also be administered using a pump (CSII), which is a device, roughly the size of a mobile phone and containing sufficient insulin to supply both the needs of basal metabolism throughout the day, and the boluses which have to cover meals. The use of CSII is expensive compared to injections, but there are important potential benefits which include improved glycaemic control, reduced risk of hypoglycaemia (low blood sugar) and a more flexible lifestyle and better quality of life. There have been no trials in adults that have compared CSII treatment with MDI where the same structured training in intensive insulin therapy has been given, so the precise benefit of the pump technology is still unclear. There is a need to establish this, and identify patients who benefit the most so that the Department of Health can calculate the proportion of adults that would benefit from CSII therapy and so ensure that commissioning bodies provide the necessary reimbursement. The aim of the trial is therefore to establish the added benefit of CSII therapy over multiple injections on glycaemic control and hypoglycaemia in individuals with Type 1 diabetes receiving similar high quality structured training (Dose Adjustment For Normal Eating:DAFNE) in insulin therapy. Additional assessments will include effects on quality of life and cost effectiveness.
The trial is a multi-centre randomised controlled trial whereby between 40 and 49 type-1 diabetic, adult volunteers, aged 18 and above, will be recruited per site from 7 secondary care centres (Sheffield, Kings College Hospital London, Harrogate District Hospital, Addenbrookes Hospital Cambridge, Glasgow Royal Infirmary, Dumfries and Galloway Royal Infirmary and Edinburgh Royal Infirmary). The sites will be required to recruit participants to at least 3 CSII DAFNE (Dose Adjustment for Normal Eating)courses and 3 MDI DAFNE courses. This will mean that in total on the trial, 140 participants are randomised to CSII and 140 to MDI. Participants will be recruited through direct approach if already on the waiting list for a DAFNE course or through advertisement in various clinics.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
267
Medtronic MiniMed Paradigm Veo Insulin pumps (X54)
Optimised MDI therapy using rapid and twice daily (Detemir/Levemir) long-acting insulin analogues
Addenbrookes Wolfson Diabetes and Endocrine Clinic, Box 281, Addenbrookes Hospital, Hills Road
Cambridge, Cambridgeshire, United Kingdom
Harrogate District Hospital, Diabetes Centre, Lancaster Park Road,
Harrogate, North Yorkshire, United Kingdom
Dumfries and Galloway Royal Infirmary, Diabetes Centre, Cluden West, Crichton Hall,
Dumfries, Scotland, United Kingdom
Royal Infirmary of Edinburgh, Department of Diabetes, 51 Little France Crescent
Edinburgh, Scotland, United Kingdom
Stobhill ACH, Diabetes Clinic, 133 Balornock Road
Glasgow, Scotland, United Kingdom
Sheffield Teaching Hospital, Diabetes Centre, Northern General Hospital, PO Box 1, Herries Road
Sheffield, South Yorkshire, United Kingdom
Kings College Hospital, Diabetes Centre, Suite 3, Golden Jubilee Wing, Denmark Hill
London, United Kingdom
Nottingham University Hospitals NHS Trust, Queens Medical Centre Campus, Derby Road
Nottingham, United Kingdom
The change in HbA1c after 2 years in those participants whose baseline HbA1c was at or above 7.5% (58mmol/mol).
The change in HbA1c after 2 years in those participants whose baseline HbA1c was at or above 7.5% (58mmol/mol). (Change will be calculated from baseline at 24 months)
Time frame: 2 years
The proportion of participants reaching the NICE target of an HbA1c level of 7.5% (58mmol/mol) or less
HbA1c is a measurement of glycosylated haemoglobin which reflects overall blood glucose values over the previous 6-8 weeks(24). This is regarded as the gold standard measure of glycaemic control. There is a strong relationship between HbA1c and the risk of developing long term diabetic complications and it is accepted as a surrogate for long term outcomes in individuals with diabetes. Since HbA1c can be measured by different techniques we will ensure standardisation by measuring HbA1c in blood samples at a central laboratory. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Diabetes specific quality of life
DSQOL Diabetes-specific quality of life (QoL) will be assessed using the scale DSQOL. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Hypoglycaemia (severe & moderate)
The investigators will record both severe and moderate episodes of hypoglycaemia in participants. This should increase power and identify the ability of CSII to reduce rates of hypoglycaemia. It will also be possible to assess the effects of both, by comparing quality of life measures in those with only moderate hypos, versus those with moderate and severe. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Insulin dose
Some studies have indicated that CSII results in the use of less insulin. We will therefore record participants' self-reported insulin dose at each time point and calculate units/kg body weight. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Body weight
If CSII treatment results in the use of less insulin, it may have a favourable effect on weight since with less insulin there is a propensity for the body to store fewer nutrients. We will therefore record weight at each time point of the trial. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Blood lipids & proteinuria
Blood samples will be taken using local labs and lipids (including HDL cholesterol). Albumin- creatinine ratio (a sensitive measure of proteinuria) will be measured from urine samples. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Diabetic Ketoacidosis
This outcome will be measured through the assessment of any SAE's and AEs. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Fear of hypoglycaemia
The Hypoglycaemia Fear Scale (HFS) is a well validated psychometric tool assessing participants fear of hypoglycaemia both overall and in terms of behaviour and worry. It has been used to assess the impacts of different hypoglycaemic events such as severe, moderate and mild hypoglycaemic episodes on fear of hypoglycaemia (33). A specific benefit to the HFS is that it may be able to identify participants who are likely to maintain high blood glucose levels, thus aiding understanding of potential reasons for poor glycaemic control. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Diabetes Treatment Satisfaction
The Diabetes Treatment Satisfaction Questionnaire (DTSQ measures treatment satisfaction which refers to an individual's subjective appraisal of their experience of treatment, including ease of use, side effects and efficacy. Improvements in satisfaction are not necessarily accompanied by improvements in QoL; treatment satisfaction can be high despite diabetes having a negative impact on QoL, which is why it is important to measure both separately. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Emotional Wellbeing
The Hospital Anxiety and Depression Scale (HADS) measures anxiety on one subscale and depression on another through the use of 7 questions for each characteristic. It is important to measure emotional wellbeing in the trial as participants may find it easier to manage their condition after DAFNE education or with one of the treatments. This might have a substantial effect on their emotional wellbeing that the QoL measures are not sensitive enough to pick up. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Participant views regarding the pump/multiple injection course & treatment
Participant post course interviews Participants will be interviewed regarding: 1. Understandings of the trial and motivation for participation. 2. Views about outcome of randomisation. 3. Expectations/concerns about trial participation and (if relevant) change to CSII. 4. Experience of/views about the course and (if relevant) change to CSII. 5. Changes they have made to diabetes management since the course and short/long terms goals set. 6. Likes/dislikes of CSII or MDI treatment. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Educator views regarding the pump/multiple injection course & treatment
Educator post course interviews Educators will be interviewed regarding: a) Insight and experience of what took place on the course. b) Recommendations for future course development. c) Recommendations for support that should be offered to patients who move onto pumps. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Costs and Outcomes
Costs and quality adjusted life years will be estimated for each individual recruited to the trial. Mean values for each arm will be calculated. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Incremental cost-effectiveness ratio
Cost-effectiveness will be described using plots of incremental costs and QALYs on the cost-effectiveness plane, together with their associated cost-effectiveness acceptability curves and frontiers. The incremental cost-effectiveness ratio and the probability that CSII will be cost-effective in the range of £20,000-£30,000 per QALY will be the main focus. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Costs
Mean values of cost wll be estimated and the value will be calculated for each individual (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
General Quality of Life
This will be measured by 3 different measures, the WHOQOL bref, SF12 and EQ5D. (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
Quality of adjusted life years
Mean values will be estimated and value will be calculated for each individual (Change will be calculated from baseline at 24 months)
Time frame: 6, 12 and 24 months
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