Understanding Beta-cell Destruction Through the Study of EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)

Status: Recruiting
Location: See all (4) locations...
Intervention Type: Other, Diagnostic test
Study Type: Observational
SUMMARY

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. 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 extends 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.

Eligibility
Participation Requirements
Sex: All
Maximum Age: 70
Healthy Volunteers: f
View:

⁃ 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.

Locations
United States
Washington
Benaroya Research Institute
NOT_YET_RECRUITING
Seattle
Other Locations
Netherlands
Leiden University Medical Center
NOT_YET_RECRUITING
Leiden
United Kingdom
Royal Devon & Exeter NHS Foundation Trust
RECRUITING
Exeter
King's College London
ACTIVE_NOT_RECRUITING
London
Contact Information
Primary
Richard Oram
r.oram@exeter.ac.uk
+44 (0) 1392 408538
Backup
Michelle Hudson
m.hudson@exeter.ac.uk
+44 (0) 1392 408181
Time Frame
Start Date: 2017-09-01
Estimated Completion Date: 2026-11-30
Participants
Target number of participants: 260
Treatments
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).
Study 1: T1D (Control)
* Age 0-70 years (matched to above)~* Clinical diagnosis of T1D (diagnosed age 1-20 years)~* Insulin treated from diagnosis.
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)
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).
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.
Related Therapeutic Areas
Sponsors
Leads: University of Exeter
Collaborators: Royal Devon and Exeter NHS Foundation Trust, Benaroya Research Institute, King's College London

This content was sourced from clinicaltrials.gov