Research

The care we deliver today has been developed by doctors, scientists and other healthcare professionals through research.

Children and young people receiving treatment today are benefitting from research that has been, and is currently being, carried out.

Developments are not possible without the support of people with diabetes and their families.

The Children's Diabetes Research Team would like to thank everybody who is participating in our research trials. We greatly appreciate your help!

Contact us

If you are interested in participating in our research studies or are keen to receive more information, please contact the Children's Research Team.

Email: ChildrensResearch@ouh.nhs.uk

Tel: 01865 231729 / 857787

Children's Research Team

Research Lead

Dr Rachel Besser

Senior Research Nurse

Jennie Moreton

Research Co-ordinator

Rebecca Beckley

Research Nurses

• Kirsten Beadon
• Rebecca Law
• Alison West
• Melanie James
• Rebecca Harmer

Diabetes Specialist Nurse Research Liaison

Jane Haest

Clinical Trial Quality Officer

Dr Julia Milano

Clinical Trial Assistant

Louise Pollard

Research trials

Here is a list of our current and recently finished research trials.

Screening for Type 1 diabetes

T1Early Programme

We are undertaking research to understand feasibility, acceptability, cost effectiveness and implementation of screening for type 1 diabetes (T1D) in the NHS.

Summary

Around 3000 children are diagnosed with T1D every year in England and Wales and require lifelong insulin injections. In most cases the early symptoms go unrecognised, and children are very unwell at diagnosis, often needing hospital admission. One in four children are already in a life-threatening condition called diabetic ketoacidosis (DKA), where the level of a chemical called ketones rises which can be dangerous. DKA needs to be treated in hospital and needs careful management. On average one child dies each year because of DKA. The rate of DKA has not changed over the last 20 years, despite public awareness campaigns. The shock of severe illness is distressing to children and their families and may also have longer term effects on the child's developing brain, health and wellbeing.

It is now possible to identify children before they develop symptoms through a finger prick blood test. This picks up markers in the blood, called 'antibodies', months or years before symptoms appear. It is also possible to identify children at risk of developing T1D, by testing for genes associated with this condition.

Research from around the world suggests that testing healthy children ('screening') for antibodies can prevent emergency admissions and DKA. However, we do not know the best approach, in terms of the age to screen, whether genetics should be included, whether screening is acceptable to the general population, how to follow up children/adults who are identified as at risk in routine clinical care, or whether this is cost-effective in the NHS. As therapies become available to delay T1D, it will be important to know who the at-risk children and adults are, who could benefit from these.

Our work aims to find out the answers, through a number of different research studies.

1. T1 Early Feasibility study

Title: Establishing the feasibility of antibody screening in primary care at the time of the pre-school vaccination, to identify children with early-onset type 1 diabetes

Funder: NIHR Oxford BRC

Chief Investigator: Dr Rachel Besser

Launched: September 2022

Summary

We are currently recruiting children between the age of 3.5-4years initially in two GP practices, in the Thames Valley, before further rollout, to test for early markers of T1D. This involves a finger prick blood test to measure for diabetes antibodies.

Study raises hope of pre-school type 1 diabetes screening programme - Department of Paediatrics

2. NIHR Programme Development grant

Title: Screening for pre-clinical type 1 diabetes to prevent hospital admission and acute illness at diagnosis: determining the evidence for benefit, acceptability and elements relevant to cost evaluation

Funder: National Institute for Health and Care Research (NIHR)

Lead: Dr Rachel Besser, Co-lead: Professor Colin Dayan

Launched: October 2022

Summary

We will review the evidence for different methods of screening and the benefits and harms of diagnosing T1D early. We will explore the acceptability of screening with a group of parents, children and young people, and specifically we will interview parents for the T1Ealry feasibility study. Finally, we will explore what the costs and potential savings of screening might be for the NHS. We will use this information in a future Programme Grant to select the best approach for screening for the NHS.

3. Follow-up in children and young people identified as at risk of future type 1 diabetes

Title: Redesigning the pathway to diagnosis in childhood type 1 diabetes (T1D)

Funder: Novo Nordisk UK Research Foundation

DPhil student: Dr Rabbi Swaby

Supervisors: Dr Rachel Besser, Professor Colin Dayan, Professor John Todd

Launched: September 2022

Summary

Screening on its own does not reduce life-threatening illness. It is screening accompanied by appropriate follow-up that does. Children identified with diabetes antibodies need regular testing to see if they are developing T1D, but the best methods to do this are uncertain. Around 50 percent of children and adults are lost to follow-up in established T1D follow-up research studies. This is likely because of the tests used and the variable time period between an individual being told they are 'at risk' and getting clinical T1D.

To understand how best to care for these children, we will undertake research to establish a general population surveillance pathway in children at high risk of developing T1D in childhood.

GPPAD-POInT Global Platform of Autoimmune Diabetes - Primary Oral Insulin Trial

Title: Oral Insulin Therapy for Prevention of Autoimmune Diabetes

Sponsor: Investigator Initiated Trial, Technische Universität München, represented by the School of Medicine

Principal Investigator UK: Dr Rachel Besser, Oxford Vaccine Group, University of Oxford

Summary

POINT is now in the follow-up phase. The study recruited infants who were screened for diabetes at birth through the INGR1D Study and have been found to be at high genetic risk for developing T1D. POInT examines whether the development of T1D can be prevented in children with an increased risk of type 1 diabetes through preventive treatment with oral insulin. The trial's aim is to see if the immune system can be trained so that it tolerates its own insulin. The overall aim is to develop ways to prevent diabetes.

GPPAD-POInT Global Platform of Autoimmune Diabetes - Primary Oral Insulin Trial

Technology

Closed Loop from Onset in Type 1 Diabetes (CLOuD) Study

This study assesses whether a closed loop insulin delivery system used from diagnosis can preserve residual beta cell function, and if this can be achieved better than standard treatment requiring multiple daily injections.

A continuous glucose monitor (CGM) continuously measures glucose levels and, additionally, insulin pumps can help with more accurate delivery of insulin. The CLOuD Study links CGM with an insulin pump, and a computer algorithm helps on a mobile phone app. The app receives information from the CGM and calculates the correct dose of background insulin. This is known as a closed loop system or an 'artificial pancreas'.

The study is also assessing quality of life, fear of hypoglycaemia and the feasibility and acceptance of a new therapy at diagnosis. The study aimed to recruit 100 participants between 10-16 years, and is now in the follow-up phase.

The study is sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge and is funded by the NIHR. Oxford is one of the six UK centres delivery the research.

For information about the first individual recruited, and how this technology has made a real difference to the lives of young people, please visit:

'Artificial pancreas' trial begins in Oxfordshire - ITV News Meridian

OUH Children's Diabetes Service featured on One Show - NIHR Oxford Biomedical Research Centre

BBC The One Show on Twitter

Prevention of complications

Adolescent Diabetes Intervention Trial (AdDIT) Follow-up Study

The AdDIT Trial is an international multi-centre randomised, double-blind, placebo-controlled trial looking at ways of preventing long-term complications with a particular focus on heart, kidney and circulatory problems, and is now in the follow-up phase. It used an angiotensin-converting enzyme (ACE) inhibitor and/or statin, in comparison to a placebo, in teenage patients.

The study is funded by the Juvenile Diabetes Research Foundation (JDRF), DUK and the British Heart Foundation. The sponsor was the University of Cambridge.

Observational studies

Bart's OXford family study (BOX)

The BOX family study is an observational population-based study following young people with T1D and their relatives. The study aims to research how and why T1D occurs.

T1D is caused when the immune system makes a mistake and targets and destroys the insulin-producing beta cells in the pancreas. Close relatives will share some of the same genes as the child who has been diagnosed with T1D and will live in the same environment. As a result, it is important to study all family members to try to understand why and how T1D develops.

The study is funded by Diabetes UK (DUK) and the Juvenile Diabetes Research Foundation (JDRF) and the study team at the University of Bristol.

Further information about the BOX study can be found here:

Bart's OXford (BOX) family study

Investigating Underlying Causal Mechanisms of Type 1 Diabetes (DMECH) Study

DMECH aims to find the genes that cause T1D and to understand the purpose of these genes. This will allow us to identify individuals at risk of developing T2D. The study compares individuals with T1D and those who do not have T1D. We hope this leads to preventative treatment in at risk individuals.

This study is recruiting children from birth, up to 16 years of age with T1D, or those who have an autoimmune or inflammatory condition or those who are at risk. The study aims to recruit 200 volunteers annually. Both adults and children who have T1D compared with healthy volunteers. Involvement in the study involves questionnaires, mouth swabs and blood tests.

The study is sponsored by the University of Oxford and is funded by the Juvenile Diabetes Research Foundation (JDRF) and Wellcome.

ADDRESS-2 Study

ADDRESS-2 aims to identify children and adults with newly diagnosed T1D who want to hear about opportunities to participate in clinical research in the future. As a result of participation, individuals can be directed towards suitable trials of new treatments amongst other studies.

Information and optional blood samples are also collected from participants. This is to understand more about the development and progression of T1D.

The study sponsor is Imperial College, London and the study is funded by the Department of Health, Diabetes UK and the Juvenile Diabetes Research Foundation (JDRF).

Further information about the ADDRESS-2 study can be found here:

ADDRESS-2

Studies recently finished

Immunotherapy

Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD) Study

T1D develops because the immune system, which helps to fight infections, attacks and destroys the beta cells that produce insulin in the pancreas. As a result, the ability of the pancreatic beta cells to produce insulin decreases, and diabetes develops.

The ITAD Study was a randomised, double-blind, placebo-controlled study. The purpose of the ITAD study is to see if a drug called aldesleukin (Interleukin-2, IL-2), which acts on the immune system, can preserve the production of insulin in children and young people, aged 6-18 years, who have been newly diagnosed with T1D. For those diagnosed with T1D, the longer they are able to produce their own insulin, the better it is for the control of blood glucose levels and the reduction of long-term complications.

The study is sponsored by the University of Oxford and is funded by the Juvenile Diabetes Research Foundation (JDRF).

TAP Study

The TAP study looked at a device which collects blood painlessly through the skin. The study assessed whether the device can be used as an alternative to a traditional blood test, which uses a needle.

In this study, the device was tested in children and adults, both with and without T1D. The TAP study measured C-peptide, a small protein that is a marker of an individual's ability to make their own insulin.

In the treatment of T1D, it is advantageous to understand if an individual can make their own C-peptide, as this can inform outcomes, and is important in research to monitor response to interventions aiming to preserve pancreatic (beta cell) function.

The study was sponsored by the University of Oxford and is funded by Oxford NIHR BRC.

Fat and Protein Study

The Fat and Protein Study assessed insulin dose adjustment based on the fat and protein content in food. This was undertaken to understand how improved blood glucose control can be achieved after children and adolescents eat high fat and protein meals, in those who use multiple daily injections.

Participants in the study were aged between 6-17 years and had been diagnosed with T1D for over one year. Participants were asked to wear a CGM for one week. During this time, participants consumed the set study meal on three evenings.

Additional rapid acting insulin for the fat and protein content of a standardised high fat high protein meal was calculated using an algorithm and was given at three tie points (+0hr, +1hr OR +2HR).

The study was sponsored by Oxford University Hospitals and funded by NovoNordisk Research Foundation.

DAN05 study: Day and night closed loop in young people with type 1 diabetes

This study assessed whether 24/7 closed loop (artificial pancreas) technology could improve glycaemic control in children and young people (aged 6-19) with T1D. The study ran over a six-month period and aimed to randomise 130 individuals to either closed loop or insulin pump therapy.

The study was sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge.

Publications

Artificial pancreas technology (CLOuD / DAN05 studies)

User Engagement With the CamAPS FX Hybrid Closed-Loop App According to Age and User Characteristics.

Adolescents' Experiences of Using a Smartphone Application Hosting a Closed-loop Algorithm to Manage Type 1 Diabetes in Everyday Life: Qualitative Study.

Data Sharing While Using a Closed-Loop System: Qualitative Study of Adolescents' and Parents' Experiences and Views.

Assessing 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 study): a randomised parallel study protocol.

What Training, Support, and Resourcing Do Health Professionals Need to Support People Using a Closed-Loop System? A Qualitative Interview Study with Health Professionals Involved in the Closed Loop from Onset in Type 1 Diabetes (CLOuD) Trial.

Health professionals' views about who would benefit from using a closed-loop system: a qualitative study.

Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial.

Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, multicentre, multinational, single-period, randomised, parallel group study protocol.

Boughton CK, Allen JM, Ware J, Wilinska ME, Hartnell S, Thankamony A, Randell T, Ghatak A, Besser REJ, Elleri D, Trevelyan N, Campbell FM, Sibayan J, Calhoun P, Bailey R, Dunseath G, Hovorka R; CLOuD Consortium. Closed-Loop Therapy and Preservation of C-Peptide Secretion in Type 1 Diabetes. N Engl J Med. 2022 Sep 8;387(10):882-893. doi: 10.1056/NEJMoa2203496. PMID: 36069870.

Hood KK, Garcia-Willingham N, Hanes S, Tanenbaum ML, Ware J, Boughton CK, Allen JM, Wilinska ME, Tauschmann M, Denvir L, Thankamony A, Campbell F, Wadwa RP, Buckingham BA, Davis N, DiMeglio LA, Mauras N, Besser REJ, Ghatak A, Weinzimer SA, Fox DS, Kanapka L, Kollman C, Sibayan J, Beck RW, Hovorka R; DAN05 Consortium. Lived experience of CamAPS FX closed loop system in youth with type 1 diabetes and their parents. Diabetes Obes Metab. 2022 Dec;24(12):2309-2318. doi: 10.1111/dom.14815. Epub 2022 Aug 8. PMID: 35837984.

BOX

Recent publications and posters - Bart's-OXford (BOX) family study

ADDRESS-2

Publications - ADDRESS-2

AdDIT

Adolescent type 1 Diabetes Cardio-renal Intervention Trial (AdDIT).

Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT): urinary screening and baseline biochemical and cardiovascular assessments.

Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT).

ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes.

Medication Adherence During Adjunct Therapy With Statins and ACE Inhibitors in Adolescents With Type 1 Diabetes.

Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1 diabetes cardio-renal interventional trial).

Fat and Protein Study

Additional insulin dosing for fat and protein in children with type 1 diabetes using multiple daily injections.

Screening for childhood Type 1 diabetes

Screening children for type 1 diabetes.

General population screening for childhood type 1 diabetes: is it time for a UK strategy?

Preventing type 1 diabetes in childhood.

Screening children for type 1 diabetes: is the UK ready? | Link to abstract

Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective.

Besser REJ, Bell KJ, Couper JJ, Ziegler AG, Wherrett DK, Knip M, Speake C, Casteels K, Driscoll KA, Jacobsen L, Craig ME, Haller MJ. ISPAD clinical practice consensus guidelines 2022: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2022 Sep 30. doi: 10.1111/pedi.13410. PMID: 36177823.

Houben J, Janssens M, Winkler C, Besser REJ, Dzygalo K, Fehn A, Hommel A, Lange K, Elding Larsson H, Lundgren M, Roloff F, Snape M, Szypowska A, Weiss A, Zapardiel-Gonzalo J, Ziegler AG, Casteels K; GPPAD study group. The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study. Pediatr Diabetes. 2022 Nov 2. doi: 10.1111/pedi.13448. PMID:

Other

Circulating C-peptide levels in living children and young people and pancreatic beta cell loss in pancreas donors across type 1 diabetes disease duration.

Exploring C-peptide loss in type 1 diabetes using growth curve analysis.

Use of self-collected capillary blood samples for islet autoantibody screening in relatives: a feasibility and acceptability study.

Screening for neonatal diabetes at day 5 of life using dried blood spot glucose measurement.

Diagnosing Type 1 diabetes in adults: Guidance from the UK T1D Immunotherapy consortium.

Frequent Monitoring of C-Peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home.

Lived experience of CamAPS FX closed loop system in youth with type 1 diabetes and their parents