Clinical trial NCT01616784: The REPOSE (Relative Effectiveness of Pumps Over MDI and Structured Education) Trial
Official title: The Relative Effectiveness of Pumps Over Multiple Dose Injections and Structured Education Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes
Keywords: Adult
Diabetes Mellitus
Type 1
Humans
Hypoglycemic Agents
Administration and Dosage
Insulin
Self Care
Health Education
Insulin Infusion Systems
Randomised controlled trial
Patient Education as Topic
Hemoglobin A
Glycosylated
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Cambridge University Hospitals NHS Foundation Trust
name: NHS Dumfries & Galloway
name: NHS Lothian
name: NHS Greater Glasgow and Clyde
name: Harrogate & District NHS Foundation Trust
name: King's College Hospital NHS Trust
name: Nottingham University Hospitals NHS Trust
name: National Institute for Health Research, United Kingdom
First posted: 2012-06-12
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Is aged 18 yrs and above.
* Have had type-1 diabetes for at least 12 months (as assessed by date clinically diagnosed).
* Is fluent in speaking, reading and understanding English.
* Has no preference to either CSII or MDI arm of the study and is happy to be randomised.
* Is currently using or willing to switch to Detemir.
* Is willing to undertake self-monitoring of blood glucose (SMBG), carbohydrate counting and insulin self-adjustment. (Enrolment staff should check that any participant with a baseline HbA1c of above 12% is willing to complete SMBG).
* Has a need for structured education to optimise diabetes control in the opinion of the investigator.

Exclusion criteria:

* Inability to give informed consent.
* Is pregnant or planning to become pregnant within the next 2 years.
* Has used CSII within the last 3 years.
* Has already completed a diabetes education course.
* Has severe needle phobia.
* Has a current history of alcohol or drug abuse.
* Has a history of heart disease within the past 3 months.
* Has hypertension that is not under control with hypertensive medication (diastolic blood pressure \>100mmHg and or sustained systolic level \>160).
* Has renal impairment with a chance of needing renal replacement therapy within the next 2 years (Enrolment staff should check that creatinine levels are not above 200 µmol/L).
* Has recurrent episodes of skin infections.
* Has serious or unstable medical or psychological conditions.
* Has taken part in any other investigational clinical trial during the 4 months prior to screening.
* Has any other issue that may preclude the participant from satisfactory participation in the study based on investigatory judgement.
* Has a strong need for pump therapy in the opinion of the investigator.

Primary outcomes:
measure: The change in HbA1c after 2 years in those participants whose baseline HbA1c was at or above 7.5% (58mmol/mol).
timeFrame: 2 years
Secondary outcomes:
measure: The proportion of participants reaching the NICE target of an HbA1c level of 7.5% (58mmol/mol) or less
timeFrame: 6, 12 and 24 months
measure: Diabetes specific quality of life
timeFrame: 6, 12 and 24 months
measure: Hypoglycaemia (severe & moderate)
timeFrame: 6, 12 and 24 months
measure: Insulin dose
timeFrame: 6, 12 and 24 months
measure: Body weight
timeFrame: 6, 12 and 24 months
measure: Blood lipids & proteinuria
timeFrame: 6, 12 and 24 months
measure: Diabetic Ketoacidosis
timeFrame: 6, 12 and 24 months
measure: Fear of hypoglycaemia
timeFrame: 6, 12 and 24 months
measure: Diabetes Treatment Satisfaction
timeFrame: 6, 12 and 24 months
measure: Emotional Wellbeing
timeFrame: 6, 12 and 24 months
measure: Participant views regarding the pump/multiple injection course & treatment
timeFrame: 6, 12 and 24 months
measure: Educator views regarding the pump/multiple injection course & treatment
timeFrame: 6, 12 and 24 months
measure: Costs and Outcomes
timeFrame: 6, 12 and 24 months
measure: Incremental cost-effectiveness ratio
timeFrame: 6, 12 and 24 months
measure: Costs
timeFrame: 6, 12 and 24 months
measure: General Quality of Life
timeFrame: 6, 12 and 24 months
measure: Quality of adjusted life years
timeFrame: 6, 12 and 24 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrookes Wolfson Diabetes and Endocrine Clinic, Box 281, Addenbrookes Hospital, Hills Road
state: Cambridgeshire
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital, Diabetes Centre, Lancaster Park Road,
state: North Yorkshire
city: Dumfries
country: United Kingdom
facility: Dumfries and Galloway Royal Infirmary, Diabetes Centre, Cluden West, Crichton Hall,
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh, Department of Diabetes, 51 Little France Crescent
state: Scotland
city: Glasgow
country: United Kingdom
facility: Stobhill ACH, Diabetes Clinic, 133 Balornock Road
state: Scotland
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospital, Diabetes Centre, Northern General Hospital, PO Box 1, Herries Road
state: South Yorkshire
city: London
country: United Kingdom
facility: Kings College Hospital, Diabetes Centre, Suite 3, Golden Jubilee Wing, Denmark Hill
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust, Queens Medical Centre Campus, Derby Road
Study officials:
affiliation: University of Sheffield
name: Simon Heller, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: REPOSE Study Group. Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE). BMJ. 2017 Mar 30;356:j1285. doi: 10.1136/bmj.j1285.
citation: Heller S, White D, Lee E, Lawton J, Pollard D, Waugh N, Amiel S, Barnard K, Beckwith A, Brennan A, Campbell M, Cooper C, Dimairo M, Dixon S, Elliott J, Evans M, Green F, Hackney G, Hammond P, Hallowell N, Jaap A, Kennon B, Kirkham J, Lindsay R, Mansell P, Papaioannou D, Rankin D, Royle P, Smithson WH, Taylor C. A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial. Health Technol Assess. 2017 Apr;21(20):1-278. doi: 10.3310/hta21200.
citation: Bradburn MJ, Lee EC, White DA, Hind D, Waugh NR, Cooke DD, Hopkins D, Mansell P, Heller SR. Treatment effects may remain the same even when trial participants differed from the target population. J Clin Epidemiol. 2020 Aug;124:126-138. doi: 10.1016/j.jclinepi.2020.05.001. Epub 2020 May 11.