Understanding extremely early-onset type 1 diabetes in infants
Understanding Beta-cell Destruction Through the Study of EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)
This study looks at infants diagnosed with extremely early-onset type 1 diabetes to see how their immune systems and genes differ from those with typical diabetes, hoping to better understand this rare condition.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 300 (estimated) |
| Ages | N/A to 70 Years |
| Sex | All |
| Sponsor | University of Exeter Academic / other |
| Locations | 4 sites (Seattle, Washington and 3 other locations) |
| Trial ID | NCT03369821 on ClinicalTrials.gov |
What this trial studies
This observational study focuses on infants diagnosed with extremely early-onset type 1 diabetes (EET1D) before the age of 2. Researchers aim to investigate the unique autoimmune mechanisms that lead to this rare form of diabetes by analyzing the immune system and genetic factors in affected individuals. The study will include both EET1D patients and control groups with typical type 1 diabetes and monogenic diabetes to compare immune function and genetic risk scores. Insights gained from this research may help to unravel the complexities of type 1 diabetes and its early onset.
Who should consider this trial
Good fit: Ideal candidates include infants and young children diagnosed with type 1 diabetes before the age of 2, as well as older individuals with a clinical diagnosis of type 1 diabetes.
Not a fit: Patients diagnosed with type 1 diabetes after the age of 20 or those with confirmed genetic mutations causing non-autoimmune neonatal diabetes may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to a better understanding of the causes of type 1 diabetes, potentially informing early interventions and treatments.
How similar studies have performed: While studies on type 1 diabetes exist, this specific focus on extremely early-onset cases is relatively novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 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. Exclusion Criteria: Study 1: * Aged \>70 years * 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: * Aged \>24 months * Clinical diagnosis of diabetes \>24 months * Intercurrent illness at time of sampling for PBMCs or RNA (see below). Non-diabetic controls: * Aged \>6 years * Diagnosis of diabetes or other autoimmune condition * Known immunological disorder * On immunosuppressive medication * 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: * Recreational drug use (excluding cannabis use more than 1 week prior to blood sampling) - drug abuse may alter T cell function * Alcohol related illness (excessive alcohol consumption may alter T cell function) * Renal failure: Creatinine \>200 (as 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: * Pregnant or lactating (as this may limit blood sampling and affect T cell function) * 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) * 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).
Where this trial is running
Seattle, Washington and 3 other locations
- Benaroya Research Institute — Seattle, Washington, United States (Not_yet_recruiting)
- Leiden University Medical Center — Leiden, Leiden, Netherlands (Not_yet_recruiting)
- Royal Devon & Exeter NHS Foundation Trust — Exeter, Devon, United Kingdom (Recruiting)
- King's College London — London, United Kingdom (Active_not_recruiting)
Study contacts
- Principal investigator: Richard Oram — University of Exeter
- Study coordinator: Richard Oram
- Email: r.oram@exeter.ac.uk
- Phone: +44 (0) 1392 408538
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.