Closed Loop from Onset in Type 1 Diabetes (CLOuD)
Research type
Research Study
Full 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 (CLOuD)
IRAS ID
205761
Contact name
Roman Hovorka
Contact email
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Research Summary
Type 1 diabetes (T1D) is characterised by an autoimmune destruction of insulin producing pancreatic beta-cells leading to insulin deficiency. At clinical diagnosis most patients still have residual pancreatic beta-islet cells, but insulin secretion usually declines within months. Residual beta-cell function is clinically important as it protects against diabetes-related complications including hypoglycaemia and retinopathy. There is clear evidence that metabolic control following onset of T1D can have a major impact on preservation of beta-islet cell function. However, intensification of insulin therapy to achieve tight controlcarries a risk of hypoglycaemia. Inadequate glycaemic control can lead to problems with brain function in the developing brain as well as increased risk of long-term complications.
We have been developing a closed loop insulin therapy system which combines real time continuous glucose monitoring with insulin pump therapy to achieve glucose responsive insulin delivery mimicking beta- cell function. The vital component of this artificial pancreas system is a computer-based algorithm that computes the amount of insulin that needs to be delivered by the pump. The closed loop approach has been successfully evaluated in children, adolescents and adults in controlled laboratory studies and in home settings. The proposed study builds on recent technological advances in closed loop insulin delivery and aims to test the impact of continued intensive metabolic control using this system on preservation of beta-cell function following the onset of T1D in children and adolescents (10-18 years old). It also aims to test the feasibility and acceptance of this therapy by this population.
96 newly diagnosed (within 10 working days), eligible subjects with T1D will be enrolled on the study from 6 UK sites and randomised 1:1 to either closed loop therapy or standard therapy. Participants will have study visits and assessments (to include recording of insulin requirements, adverse event recording, blood sampling) every 3 months for a total of 24 months.Lay summary of study results
Background:
The CLOuD study, led by Professor Roman Hovorka at the University of Cambridge, was conducted between 2016 and 2023 and aimed to determine whether better glucose control using hybrid closed-loop (CL) therapy could help preserve insulin production (measured by C-peptide levels) compared to standard insulin therapy in young people with newly diagnosed type 1 diabetes (T1D).Research Design and Methods:
This study followed 97 youth with T1D aged 10 to 16.9 years for 48 months. Participants were randomly assigned to either the hybrid closed-loop group, which uses an automated insulin delivery system, or the control group, which used standard insulin injections. After the first 24 months, participants were invited to continue in an extension phase using their assigned therapy. The study’s focus was on C-peptide levels (a marker for insulin production) and overall glucose control.Results:
Out of 97 participants with T1D, 51 received closed-loop therapy, while 46 used standard insulin therapy. By the end of the first 24 months, 85 participants completed the primary study, and 81 continued into the extension phase.
After 12 months, there was no significant difference in C-peptide levels between the two groups. The closed-loop group had an average level of 0.35 pmol/mL, and the control group had 0.46 pmol/mL. The results were similar after 24 months and at the end of the study after four years, with no notable difference in C-peptide levels.
However, the closed-loop group had better overall glucose control. Their average HbA1c (a measure of blood sugar levels) was 0.9% lower than the control group, and they spent 12% more time in the target blood glucose range. There were no major differences in the number of severe low blood sugar events or diabetic ketoacidosis episodes between the two groups during the extension phase.Conclusions:
In young people with newly diagnosed type 1 diabetes, intensive glucose control using closed-loop therapy did not prevent the decline in insulin production (C-peptide levels) over time. However, the closed-loop insulin delivery did result in better long-term blood glucose control compared to standard insulin therapy in youth with type 1 diabetes.More information about the study can be found at: Study Details | Closed Loop From Onset in Type 1 Diabetes | ClinicalTrials.gov and Closed-Loop Therapy and Preservation of C-Peptide Secretion in Type 1 Diabetes - PubMed (nih.gov).
REC name
East of England - Cambridge East Research Ethics Committee
REC reference
16/EE/0286
Date of REC Opinion
5 Aug 2016
REC opinion
Further Information Favourable Opinion