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Studies immune system in babies who develop type 1 diabetes very early

Studies immune cells and insulin production in very young people with type 1 diabetes.

Key facts

Who runs it
University of Exeter
Where
Seattle, United StatesSee the siteAlso in 2 other countries, 3 sites
Trial code
Registry title
EXtremely Early-onset Type 1 Diabetes EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)
Status
Recruiting
People taking part
300 people, planned
Started
19 Sept 2017
Expected to end
30 Nov 2028
Type of study
Observational, 5 groups
Treatments tested
  • Beta Cell Loss and Immune Function
  • Immune Function with RNAseq
Record updated
19 December 2025

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for people who developed type 1 diabetes extremely early, before age 2. It also takes some controls with other kinds of diabetes and young children without diabetes.

Age
0 to 70 years. The group diagnosed with extremely early-onset diabetes in study 2 is aged 0 to 24 months. Children without diabetes are aged 0 to 6 years.
Sex
All sexes can join.
Disease stage
Diabetes diagnosed before 24 months of age, with a type 1 diabetes genetic risk score above the 50th centile or a single-gene cause of type 1 diabetes. Control groups are type 1 diabetes diagnosed at age 1 to 20 years, or single-gene or neonatal diabetes diagnosed before 12 months.
Earlier treatment
Control participants with type 1 diabetes must have been treated with insulin from diagnosis. People cannot join if they take steroids or other immune-suppressing medicines, or had immunoglobulin or blood products in the last 3 months; this may only mean a delay.
Biomarker or test result
A negative genetic test for mutations causing non-autoimmune neonatal diabetes is needed if diabetes was diagnosed before 12 months. A type 1 diabetes genetic risk score above the 50th centile or a single-gene cause of type 1 diabetes is needed.

Main reasons for not taking part

  • Aged over 70 years in study 1, or over 24 months in study 2 (over 6 years for children without diabetes)
  • MODY, type 2 diabetes, diabetes from pancreas problems, or syndromic diabetes
  • Illness at the time of blood sampling; a recent infection or fever may delay the visit
  • Kidney failure, drug abuse, or alcohol-related illness
  • Children without diabetes: autoimmune or immune disorders, immune-suppressing medicine, or major birth abnormality

The registry criteria, word for word

Show all 44 criteriaShow less

Who can take part

  • Study 1:
  • EET1D
  • Aged 0 to 70 years
  • Clinical diagnosis of diabetes <24 months (+ evidence of WHO diabetes criteria)
  • Negative genetic test for mutations causing non-autoimmune neonatal diabetes if diagnosed <12 months
  • Type 1 diabetes genetic risk score >50th centile of T1D reference group, or monogenic cause of T1D; T1D Controls
  • Age 0-70 years (matched to above)
  • Clinical diagnosis of T1D (diagnosed age 1-20 years)
  • Insulin treated from diagnosis; Monogenic / NDM controls
  • Diagnosis of diabetes <12 months
  • Diagnosis of monogenic / NDM (confirmed by Exeter Molecular Genetics Laboratory); Study 2:; EET1D
  • Aged 0 to 24 months at recruitment
  • Clinical diagnosis of diabetes <24 months (+ evidence of WHO diabetes criteria)
  • Negative genetic test for mutations causing non-autoimmune neonatal diabetes
  • Type 1 diabetes genetic risk score >50th centile of T1D reference group, or monogenic cause of T1D; Monogenic/NDM controls
  • Diagnosis of diabetes <24 months
  • Age 0 to 18 months at recruitment
  • Diagnosis of monogenic/NDM (confirmed by Exeter Molecular Genetics Laboratory); Non-diabetic controls
  • Aged 0-6 years
  • Attending specified participating hospital sites for elective surgery, including but not limited to: inguinal hernia repair, umbilical/midline hernia repair, orchidopexy, gastrostomy insertion/change, hypospadias repair, cleft palate repair, excision of accessory digit, laryngoscopy, adenoidectomy, tonsillectomy, MRI under general anaesthesia, eye surgery

Who cannot take part

  • On immunosuppressive medication
  • Recreational drug use (excluding cannabis use more than 1 week prior to blood sampling) - drug abuse may alter T cell function
  • Taking steroids or other immunosuppressive medications (as these may alter T cell function)
  • Received any immunoglobulin treatments or blood products in the last 3 months (as these may alter T cell function)
  • No diagnosis of diabetes
  • MODY (e.g. caused by HNF1A/HNF4A/HNF1B/GCK mutations), type 2 diabetes or diabetes related to pancreatic insufficiency or syndromic diabetes
  • Intercurrent illness at time of sampling for PBMCs (see below); Study 2:
  • Clinical diagnosis of diabetes >24 months
  • Intercurrent illness at time of sampling for PBMCs or RNA (see below); Non-diabetic controls:
  • Diagnosis of diabetes or other autoimmune condition
  • Known immunological disorder
  • Ongoing infections/sepsis
  • Major congenital abnormality or significant systemic illness that may affect the immune system, e.g. metabolic disease, 22q deletion syndrome
  • Recent (within two weeks) febrile illness
  • Renal failure; For PBMC and RNA sampling: Exclusion for factors that may alter T cell function and RNAseq; Review the following exclusion criteria carefully at time of appointment as some details may have changed since initial contact:
  • Alcohol related illness (excessive alcohol consumption may alter T cell function)
  • Any other medical condition which, in the opinion of the investigator, would affect the safety of the subject's participation; Factors that if temporary would lead to rearrangement of study visit but if long duration, may lead to exclusion subject to the CI's discretion:
  • Any infectious illness within the last 2 weeks if it was a febrile illness, or within 2-3 days if it was non-febrile (as this may activate T cells non-specifically)
  • Renal failure: Creatinine >200 (as may alter T cell function)
  • Aged >70 years
  • Aged >24 months
  • Aged >6 years
  • Study 1:
  • Pregnant or lactating (as this may limit blood sampling and affect T cell function)

Where in United States

Also in 2 other countries, 3 sites

  • Benaroya Research InstituteSeattle, United StatesContact: Cate SpeakeNot yet recruiting

About the trial

What the trial wants to find out

Type 1 diabetes (T1D) results from destruction of insulin-producing beta cells in the pancreas by the body's own immune system (autoimmunity). It is not fully understood what causes this type of diabetes and why there is variation in age of onset and severity between people who develop the disease. The aim of this work is to study very unusual people who develop T1D extremely young, as babies under 2 years of age (EET1D). The investigators think that, for the condition to have developed that early, they must have an unusual or extreme form of autoimmunity.

Read full original descriptionShow less

Studying people with EET1D will enable us to look at exactly what goes wrong with the immune system because they have one of the most extreme forms of the disease. Much may be learned about the disease from a small number of rare individuals. The investigators aim to confirm that they have autoimmune type 1 diabetes and then try to understand how they have developed diabetes so young by studying their immune system genes, the function of their immune system, and environmental factors (such as maternal genetics) that may play a role in their development of the disease.

People with diabetes diagnosed under 12 months are very rare, live all over the world. and are usually referred to Exeter for genetic testing. Individuals will be contacted via their clinician to ask for more information about their diabetes and their family history. Samples will be collected to study whether they still make any of their own insulin and whether they make specific antibodies against their beta cells in the pancreas. Separately, their immune system will be studied in depth using immune cells isolated from a blood sample. These cells will undergo cutting edge techniques by Dr Tim Tree at King's College London, by Professor Bart Roep at Leiden University Medical Center, Netherlands, and Dr Cate Speake, Benaroya Research Institute, Seattle (USA). Some of these tests have never been used in people of young ages around the world, so an aim of this project will be to develop methods that can be used to study people even if they live far away.

Additional funding extended the study for a further 3 years (Phase 2) to include recruitment of infants without diabetes, aged 0-6 years, as controls to enable assessment of how the abnormalities found in autoimmune and non-autoimmune diabetes compare to normal early life development of the immune system.

An additional funding award extended the study (Phase 3) until November 2028, to advance the EXE-T1D program into its third phase, building on major discoveries from phases 1 and 2 to identify, validate, and target immune pathways that drive extremely early-onset type 1 diabetes (eeT1D) and are likely relevant to T1D across all ages. eeT1D cases, diagnosed within the first two years of life, represent particularly aggressive onset of beta-cell autoimmunity. They offer a unique lens to uncover mechanisms of immune dysregulation, informed by both polygenic and monogenic causes. The central aim is to move from pathway discovery to demonstration of novel druggable targets with potential to delay or prevent T1D onset across all ages.

The 5 groups in the trial

  • Study 1: Existing EET1D (Case)

    * Aged 0 to 70 years * Clinical diagnosis of diabetes \<24 months (+ evidence of WHO diabetes criteria) * Negative genetic test for mutations causing non-autoimmune neonatal diabetes if diagnosed \<12 months * Type 1 diabetes genetic risk score \>50th centile of T1D reference group, or monogenic cause of T1D (e.g. STAT3 or FOXP3 mutation).

    Treatment: Beta Cell Loss and Immune Function and Immune Function with RNAseq

  • Study 1: T1D (Control)

    * Age 0-70 years (matched to above) * Clinical diagnosis of T1D (diagnosed age 1-20 years) * Insulin treated from diagnosis.

    Treatment: Beta Cell Loss and Immune Function and Immune Function with RNAseq

  • Study 2: Newly diagnosed EET1D (Case)

    * Aged 0 to 24 months at recruitment * Clinical diagnosis of diabetes \<24 months (+ evidence of WHO diabetes criteria) * Negative genetic test for mutations causing non-autoimmune neonatal diabetes * Type 1 diabetes genetic risk score \>50th centile of T1D reference group, or monogenic cause of T1D (e.g. STAT3 or FOXP3 mutation)

    Treatment: Beta Cell Loss and Immune Function and Immune Function with RNAseq

  • Monogenic / NDM (Control)

    * Diagnosis of diabetes \<24 months * Age 0 to 24 months at recruitment * Diagnosis of Monogenic / NDM (confirmed by Exeter Molecular Genetics Laboratory).

    Treatment: Beta Cell Loss and Immune Function and Immune Function with RNAseq

  • Without diabetes (Control)

    * Aged 0-6 years * Attending specified participating hospital sites for elective surgery, including but not limited to: inguinal hernia repair, umbilical/midline hernia repair, orchidopexy, gastrostomy insertion/change, hypospadias repair, cleft palate repair, excision of accessory digit, laryngoscopy, adenoidectomy, tonsillectomy, MRI under general anaesthesia, eye surgery. Should recruitment be slower than anticipated, we would recruit children with congenital non-immune thyroid disease when they attend paediatric clinic for blood draw.

    Treatment: Beta Cell Loss and Immune Function and Immune Function with RNAseq

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov.
Official title
Understanding Beta-cell Destruction Through the Study of EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)
Plain-language title
Studies immune system in babies who develop type 1 diabetes very earlyGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Record updated
19 December 2025