Type 1 DiabetesINCEPTiONNCT06006468
Evaluating ImmuNe Changes in the Evolution of Pre Type 1 Diabetes With Adult ONset
An observational study of Type 1 Diabetes and Type 1 Diabetes Mellitus Maturity Onset, run by Royal Devon and Exeter NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Little is known about how type 1 diabetes or coeliac disease develop in adults. Studies following children at risk of type 1 diabetes from birth have shown that the marker of type 1 diabetes autoimmunity (antibodies against the insulin producing cells in the pancreas (Glutamic Acid Decarboxylase Autoantibodies (GADA)… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes, Type 1 Diabetes Mellitus Maturity Onset
- What is being tested?
- High genetic risk for type 1 diabetes and High gentic risk for Coeliac disease
- How many people
- 2,250 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2023to 31 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: This study will use samples and data from the Exeter 10,000 cohort, a research bank of adult volunteers (https://exetercrfnihr.org/about/exeter-10000/). Stored serum samples are available (allowing islet autoantibody measurement) for all participants including ∼8000 participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3 years since recruitment)). Additionally all participants have genotype data available and have given permission to the research team to prospectively access their health records.
Who may be able to join
- Exeter 10,000 study participants with stored serum samples
- Consent for samples \& data to be used in further research.
Who cannot join
- Diagnosed with diabetes at time of original sample collection
- Diagnosed with coeliac disease at time of original sample collection
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
NIHR Exeter Clinical Research Facility (Royal Devon University Healthcare NHS Foundation Trust)
Exeter, Devon, EX2 5DW
About this study
Official title: Evaluating ImmuNe Changes in the Evolution of Pre Type 1 Diabetes With Adult Onset
Little is known about how type 1 diabetes or coeliac disease develop in adults. Studies following children at risk of type 1 diabetes from birth have shown that the marker of type 1 diabetes autoimmunity (antibodies against the insulin producing cells in the pancreas (Glutamic Acid Decarboxylase Autoantibodies (GADA), Insulin Autoantibodies (IAA), Zinc Transporter 8 Autoantibodies (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2 (IA-2))) can develop many years before glucose levels are raised and diabetes is diagnosed. In adults, it is unclear when antibodies develop in relation to high blood glucose levels and the diagnosis of type 1 diabetes.
Similarly in coeliac disease it is unclear to what degree Tissue transglutaminase autoantibodies (TTG) in adults proceed the development of clinically diagnosed disease.
Read more
The investigators will use samples collected and stored in The Exeter 10,000 volunteer research bank (https://exetercrfnihr.org/about/exeter-10000/) and so no new sample collection is required. This includes ~8000 participants with no history of coeliac disease or diabetes at recruitment. The investigators wish to determine prevalence of autoantibodies in the background adult population split by the highest genetic risk for type 1 diabetes and separately coeliac disease compared to a control population with lower genetic risk for these conditions. The investigators will also evaluate the proportion of these identified cases progressing to clinically diagnosed disease.
The aim of this study is to investigate evidence of autoimmunity prior to disease development and generate pilot data for the validity of screening based on genetic predisposition for type 1 diabetes and coeliac disease.
Read the detailed description
Detecting the early stages of type 1 diabetes in children is possible and has positive implications for clinical care.
Studies following children at risk of type 1 diabetes from birth have shown that islet autoantibodies against (Glutamic Acid Decarboxylase (GADA), Insulin (IAA), Zinc Transporter 8 (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2 (IA-2))) can develop many years before diabetes is diagnosed. This makes islet-autoantibodies an excellent biomarker of early disease with the development of multiple (≥2) positive islet-autoantibodies marking the first stage of type 1 diabetes. Many studies in children have looked at strategies for increasing islet autoantibody detection given the high numbers needed to test if screening at the whole population level. This includes targeting for autoantibody testing those with a type 1 diabetes: family history and/or raised genetic risk. Identifying type 1 diabetes early matters as it can reduce the proportion of cases presenting with severe symptoms including with diabetic ketoacidosis. This is coupled to recent FDA approval of Teplizumab therapy aiming to slow down the progression of early type 1 diabetes.
Little is known about the early development or early case detection of type 1 diabetes in adults despite representing the majority of all cases. Despite the potential benefits of pre-clinical type 1 diabetes detection in children very little is known about the stages of development of type 1 diabetes in adults. Therefore as noted in a recent Type 1 Diabetes research Steering Committee meeting "The optimal strategies for identification of at-risk adults needs to be studied". This is despite over half of all type 1 diabetes cases developing in adults. Our recent work examining adult-onset type 1 diabetes at presentation suggests that when adult-onset type 1 diabetes cases are defined robustly, characteristics include high type 1 diabetes genetic risk, rapid progression of C-peptide loss and high (>90%) rates of islet autoantibody positivity. Of these adult autoantibody positive cases ~60% were multi-autoantibody positive. Previous literature suggesting type 1 diabetes is a more benign disease in older adults likely reflects the increasingly recognised misclassification of clinically defined type 1 diabetes cases in this age group.
The high rates of islet autoantibodies at diagnosis and associated high genetic risk in adult-onset type 1 diabetes cases suggests targeted screening for early disease in this age group, using these biomarkers as undertaken in children, is a possibility. Studies recruiting first degree relatives of individuals have included adults (typically up to 45 years of age) showing detection of individuals at risk of type 1 diabetes is possible, even if progression from stage 1 to clinical disease appears reduced with increasing age at autoantibody detection. However, as in children, the majority of type 1 diabetes cases in adults develop in those without a family history of the disease and therefore genetic risk guided screening offers an attractive alternative strategy but research into the validity of this approach is lacking.
Little is known about early Coeliac disease development in adults. Coeliac disease is similarly increasingly recognised in adults but the early development of the disease is unclear. Development of coeliac disease is associated with raised genetic risk which can be captured by a coeliac genetic risk score. Recognition of coeliac disease is difficult particularly in adults and early detection has been suggested to be associated with improved outcomes.
Datasets with genetics and stored samples allow pragmatic insights into the feasibility of targeted screening for early adult-onset type 1 diabetes and coeliac disease.
The investigators will use samples collected and stored in The Exeter 10,000 adult volunteer research bank (https://exetercrfnihr.org/about/exeter-10000/) which includes ∼8000 participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3 years since recruitment)). This will allow islet autoantibody measurement without the need for additional sample collection. All participants have genotype data available and have given permission for the Exeter 10,000 team to prospectively access their health records. This dataset allows a pragmatic and cost-effective assessment of using genetic predisposition to type 1 diabetes and coeliac disease to guide islet-autoantibody/ tissue-transglutaminase testing in adults. This will provide vital pilot data which can help guide future screening strategies for detecting pre-clinical type 1 diabetes and coeliac disease in adults.
- Being tested
- High genetic risk for type 1 diabetes, High gentic risk for Coeliac disease
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High genetic risk for type 1 diabetesGenetic
in individuals without diabetes comparison of prevalence of islet auto antibodies between individuals at high genetic risk of type 1 diabetes versus controls
High gentic risk for Coeliac diseaseGenetic
in individuals without Coeliac disease comparison of prevalence of anti tissue transglutaminase antibodies between individuals at high genetic risk of coeliac disease versus controls
| Study group | Role | What they receive |
|---|---|---|
| Genetic risk of Type 1 diabetes | 750 individuals with the highest type 1 diabetes genetic risk Receives: Genetic: High genetic risk for type 1 diabetes | |
| Genetic risk of coeliac disease | 750 individuals with the highest coeliac disease genetic risk Receives: Genetic: High gentic risk for Coeliac disease | |
| Controls | 750 individuals with Neutral type 1 diabetes and coeliac disease genetic risk |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of multi-islet autoantibody positive participants
≥2 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes
Measured: through sample analysis, approx 6 months
Secondary outcomes (4)
Number of islet autoantibody positive participants
≥1 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes
Measured: through sample analysis, approx 6 months
Number of multi-islet autoantibody positive participants developing Diabetes
number of cases developing type 1 diabetes
Measured: through study follow up an average of 10 years
Number of participants with positive Tissue transglutaminase autoantibodies
Number of positive Tissue transglutaminase autoantibody in genetic risk groups for coeliac disease
Measured: through sample analysis, approx 6 months
Number of participants developing Coeliac disease
number of cases developing Coeliac disease
Measured: through study follow up an average of 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2023
- Study start1 Feb 2023
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 2,250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Devon and Exeter NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Exeter
- Responsible party
- Sponsor
- Investigators
- Richard Oram, Dr, Principal investigator, University of Exeter & Royal Devon University Healthcare NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06006468
- Sponsor's protocol ID
- CRF525
- Acronym
- INCEPTiON
- Status last verified
- Jun 2024
- First submitted
- 20 Jun 2023
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Extend data available through external application process to university of Exeter
Publications
Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, Greenbaum CJ, Herold KC, Krischer JP, Lernmark A, Ratner RE, Rewers MJ, Schatz DA, Skyler JS, Sosenko JM, Ziegler AG. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015 Oct;38(10):1964-74. doi: 10.2337/dc15-1419.
PubMed 26404926Ziegler AG, Rewers M, Simell O, Simell T, Lempainen J, Steck A, Winkler C, Ilonen J, Veijola R, Knip M, Bonifacio E, Eisenbarth GS. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013 Jun 19;309(23):2473-9. doi: 10.1001/jama.2013.6285.
PubMed 23780460Orban T, Sosenko JM, Cuthbertson D, Krischer JP, Skyler JS, Jackson R, Yu L, Palmer JP, Schatz D, Eisenbarth G; Diabetes Prevention Trial-Type 1 Study Group. Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care. 2009 Dec;32(12):2269-74. doi: 10.2337/dc09-0934. Epub 2009 Sep 9.
PubMed 19741189Steck AK, Vehik K, Bonifacio E, Lernmark A, Ziegler AG, Hagopian WA, She J, Simell O, Akolkar B, Krischer J, Schatz D, Rewers MJ; TEDDY Study Group. Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care. 2015 May;38(5):808-13. doi: 10.2337/dc14-2426. Epub 2015 Feb 9.
PubMed 25665818Sims EK, Besser REJ, Dayan C, Geno Rasmussen C, Greenbaum C, Griffin KJ, Hagopian W, Knip M, Long AE, Martin F, Mathieu C, Rewers M, Steck AK, Wentworth JM, Rich SS, Kordonouri O, Ziegler AG, Herold KC; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022 Apr 1;71(4):610-623. doi: 10.2337/dbi20-0054.
PubMed 35316839Ziegler AG, Kick K, Bonifacio E, Haupt F, Hippich M, Dunstheimer D, Lang M, Laub O, Warncke K, Lange K, Assfalg R, Jolink M, Winkler C, Achenbach P; Fr1da Study Group. Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany. JAMA. 2020 Jan 28;323(4):339-351. doi: 10.1001/jama.2019.21565.
PubMed 31990315Mahon JL, Sosenko JM, Rafkin-Mervis L, Krause-Steinrauf H, Lachin JM, Thompson C, Bingley PJ, Bonifacio E, Palmer JP, Eisenbarth GS, Wolfsdorf J, Skyler JS; TrialNet Natural History Committee; Type 1 Diabetes TrialNet Study Group. The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results. Pediatr Diabetes. 2009 Apr;10(2):97-104. doi: 10.1111/j.1399-5448.2008.00464.x. Epub 2008 Sep 24.
PubMed 18823409Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes. 1999 Mar;48(3):460-8. doi: 10.2337/diabetes.48.3.460.
PubMed 10078544Hagopian WA, Erlich H, Lernmark A, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt R Jr, Blair A, Ilonen J, Krischer J, She J; TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011 Dec;12(8):733-43. doi: 10.1111/j.1399-5448.2011.00774.x. Epub 2011 May 12.
PubMed 21564455Ziegler AG, Danne T, Dunger DB, Berner R, Puff R, Kiess W, Agiostratidou G, Todd JA, Bonifacio E. Primary prevention of beta-cell autoimmunity and type 1 diabetes - The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) perspectives. Mol Metab. 2016 Feb 22;5(4):255-262. doi: 10.1016/j.molmet.2016.02.003. eCollection 2016 Apr.
PubMed 27069865Winkler C, Schober E, Ziegler AG, Holl RW. Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. Pediatr Diabetes. 2012 Jun;13(4):308-13. doi: 10.1111/j.1399-5448.2011.00829.x. Epub 2011 Nov 8.
PubMed 22060727Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 Aug 15;381(7):603-613. doi: 10.1056/NEJMoa1902226. Epub 2019 Jun 9.
PubMed 31180194Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA, Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. Lancet Diabetes Endocrinol. 2018 Feb;6(2):122-129. doi: 10.1016/S2213-8587(17)30362-5. Epub 2017 Nov 30.
PubMed 29199115Diaz-Valencia PA, Bougneres P, Valleron AJ. Global epidemiology of type 1 diabetes in young adults and adults: a systematic review. BMC Public Health. 2015 Mar 17;15:255. doi: 10.1186/s12889-015-1591-y.
PubMed 25849566Harding JL, Wander PL, Zhang X, Li X, Karuranga S, Chen H, Sun H, Xie Y, Oram RA, Magliano DJ, Zhou Z, Jenkins AJ, Ma RCW. The Incidence of Adult-Onset Type 1 Diabetes: A Systematic Review From 32 Countries and Regions. Diabetes Care. 2022 Apr 1;45(4):994-1006. doi: 10.2337/dc21-1752.
PubMed 35349653
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating ImmuNe Changes in the Evolution of Pre Type 1 Diabetes With Adult Onset
- ClinicalTrials.gov ID
- NCT06006468
- Acronym / sponsor ID
- INCEPTiON / CRF525
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2,250 participants (actual)
- Lead sponsor
- Royal Devon and Exeter NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Exeter
- Study start
- 1 Feb 2023 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 23 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Little is known about how type 1 diabetes or coeliac disease develop in adults. Studies following children at risk of type 1 diabetes from birth have shown that the marker of type 1 diabetes autoimmunity (antibodies against the insulin producing cells in the pancreas (Glutamic Acid Decarboxylase Autoantibodies (GADA), Insulin Autoantibodies (IAA), Zinc Transporter 8 Autoantibodies (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2 (IA-2))) can develop many years before glucose levels are raised and diabetes is diagnosed. In adults, it is unclear when antibodies develop in relation to high blood glucose levels and the diagnosis of type 1 diabetes.
Similarly in coeliac disease it is unclear to what degree Tissue transglutaminase autoantibodies (TTG) in adults proceed the development of clinically diagnosed disease.
The investigators will use samples collected and stored in The Exeter 10,000 volunteer research bank (https://exetercrfnihr.org/about/exeter-10000/) and so no new sample collection is required. This includes ~8000 participants with no history of coeliac disease or diabetes at recruitment. The investigators wish to determine prevalence of autoantibodies in the background adult population split by the highest genetic risk for type 1 diabetes and separately coeliac disease compared to a control population with lower genetic risk for these conditions. The investigators will also evaluate the proportion of these identified cases progressing to clinically diagnosed disease.
The aim of this study is to investigate evidence of autoimmunity prior to disease development and generate pilot data for the validity of screening based on genetic predisposition for type 1 diabetes and coeliac disease.
Detailed description
Detecting the early stages of type 1 diabetes in children is possible and has positive implications for clinical care.
Studies following children at risk of type 1 diabetes from birth have shown that islet autoantibodies against (Glutamic Acid Decarboxylase (GADA), Insulin (IAA), Zinc Transporter 8 (ZnT8), Anti-tyrosine phosphatase-like insulinoma antigen 2 (IA-2))) can develop many years before diabetes is diagnosed. This makes islet-autoantibodies an excellent biomarker of early disease with the development of multiple (≥2) positive islet-autoantibodies marking the first stage of type 1 diabetes. Many studies in children have looked at strategies for increasing islet autoantibody detection given the high numbers needed to test if screening at the whole population level. This includes targeting for autoantibody testing those with a type 1 diabetes: family history and/or raised genetic risk. Identifying type 1 diabetes early matters as it can reduce the proportion of cases presenting with severe symptoms including with diabetic ketoacidosis. This is coupled to recent FDA approval of Teplizumab therapy aiming to slow down the progression of early type 1 diabetes.
Little is known about the early development or early case detection of type 1 diabetes in adults despite representing the majority of all cases. Despite the potential benefits of pre-clinical type 1 diabetes detection in children very little is known about the stages of development of type 1 diabetes in adults. Therefore as noted in a recent Type 1 Diabetes research Steering Committee meeting "The optimal strategies for identification of at-risk adults needs to be studied". This is despite over half of all type 1 diabetes cases developing in adults. Our recent work examining adult-onset type 1 diabetes at presentation suggests that when adult-onset type 1 diabetes cases are defined robustly, characteristics include high type 1 diabetes genetic risk, rapid progression of C-peptide loss and high (>90%) rates of islet autoantibody positivity. Of these adult autoantibody positive cases ~60% were multi-autoantibody positive. Previous literature suggesting type 1 diabetes is a more benign disease in older adults likely reflects the increasingly recognised misclassification of clinically defined type 1 diabetes cases in this age group.
The high rates of islet autoantibodies at diagnosis and associated high genetic risk in adult-onset type 1 diabetes cases suggests targeted screening for early disease in this age group, using these biomarkers as undertaken in children, is a possibility. Studies recruiting first degree relatives of individuals have included adults (typically up to 45 years of age) showing detection of individuals at risk of type 1 diabetes is possible, even if progression from stage 1 to clinical disease appears reduced with increasing age at autoantibody detection. However, as in children, the majority of type 1 diabetes cases in adults develop in those without a family history of the disease and therefore genetic risk guided screening offers an attractive alternative strategy but research into the validity of this approach is lacking.
Little is known about early Coeliac disease development in adults. Coeliac disease is similarly increasingly recognised in adults but the early development of the disease is unclear. Development of coeliac disease is associated with raised genetic risk which can be captured by a coeliac genetic risk score. Recognition of coeliac disease is difficult particularly in adults and early detection has been suggested to be associated with improved outcomes.
Datasets with genetics and stored samples allow pragmatic insights into the feasibility of targeted screening for early adult-onset type 1 diabetes and coeliac disease.
The investigators will use samples collected and stored in The Exeter 10,000 adult volunteer research bank (https://exetercrfnihr.org/about/exeter-10000/) which includes ∼8000 participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3 years since recruitment)). This will allow islet autoantibody measurement without the need for additional sample collection. All participants have genotype data available and have given permission for the Exeter 10,000 team to prospectively access their health records. This dataset allows a pragmatic and cost-effective assessment of using genetic predisposition to type 1 diabetes and coeliac disease to guide islet-autoantibody/ tissue-transglutaminase testing in adults. This will provide vital pilot data which can help guide future screening strategies for detecting pre-clinical type 1 diabetes and coeliac disease in adults.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Genetic risk of Type 1 diabetes | – | Genetic: High genetic risk for type 1 diabetes750 individuals with the highest type 1 diabetes genetic risk |
| Genetic risk of coeliac disease | – | Genetic: High gentic risk for Coeliac disease750 individuals with the highest coeliac disease genetic risk |
| Controls | – | –750 individuals with Neutral type 1 diabetes and coeliac disease genetic risk |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study will use samples and data from the Exeter 10,000 cohort, a research bank of adult volunteers (https://exetercrfnihr.org/about/exeter-10000/). Stored serum samples are available (allowing islet autoantibody measurement) for all participants including ∼8000 participants with no history of diabetes at recruitment (a median 10 years ago (minimum 3 years since recruitment)). Additionally all participants have genotype data available and have given permission to the research team to prospectively access their health records.
Key inclusion criteria (2 listed)
- Exeter 10,000 study participants with stored serum samples
- Consent for samples \& data to be used in further research.
Key exclusion criteria (2 listed)
- Diagnosed with diabetes at time of original sample collection
- Diagnosed with coeliac disease at time of original sample collection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High genetic risk for type 1 diabetesin individuals without diabetes comparison of prevalence of islet auto antibodies between individuals at high genetic risk of type 1 diabetes versus controls | Genetic | Genetic risk of Type 1 diabetes |
| High gentic risk for Coeliac diseasein individuals without Coeliac disease comparison of prevalence of anti tissue transglutaminase antibodies between individuals at high genetic risk of coeliac disease versus controls | Genetic | Genetic risk of coeliac disease |
Primary outcome
Number of multi-islet autoantibody positive participants
Time frame: through sample analysis, approx 6 months
≥2 positive islet autoantibodies (GAD, IA-2, ZNT8, IAA) between genetic risk groups for type 1 diabetes
4 secondary outcomes
Number of islet autoantibody positive participants
Time frame: through sample analysis, approx 6 months
Number of multi-islet autoantibody positive participants developing Diabetes
Time frame: through study follow up an average of 10 years
Number of participants with positive Tissue transglutaminase autoantibodies
Time frame: through sample analysis, approx 6 months
Number of participants developing Coeliac disease
Time frame: through study follow up an average of 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- Background: PubMed 26404926Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, Greenbaum CJ, Herold KC, Krischer JP, Lernmark A, Ratner RE, Rewers MJ, Schatz DA, Skyler JS, Sosenko JM, Ziegler AG. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015 Oct;38(10):1964-74. doi: 10.2337/dc15-1419.
- Background: PubMed 23780460Ziegler AG, Rewers M, Simell O, Simell T, Lempainen J, Steck A, Winkler C, Ilonen J, Veijola R, Knip M, Bonifacio E, Eisenbarth GS. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013 Jun 19;309(23):2473-9. doi: 10.1001/jama.2013.6285.
- Background: PubMed 19741189Orban T, Sosenko JM, Cuthbertson D, Krischer JP, Skyler JS, Jackson R, Yu L, Palmer JP, Schatz D, Eisenbarth G; Diabetes Prevention Trial-Type 1 Study Group. Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial-Type 1. Diabetes Care. 2009 Dec;32(12):2269-74. doi: 10.2337/dc09-0934. Epub 2009 Sep 9.
- Background: PubMed 25665818Steck AK, Vehik K, Bonifacio E, Lernmark A, Ziegler AG, Hagopian WA, She J, Simell O, Akolkar B, Krischer J, Schatz D, Rewers MJ; TEDDY Study Group. Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care. 2015 May;38(5):808-13. doi: 10.2337/dc14-2426. Epub 2015 Feb 9.
- Background: PubMed 35316839Sims EK, Besser REJ, Dayan C, Geno Rasmussen C, Greenbaum C, Griffin KJ, Hagopian W, Knip M, Long AE, Martin F, Mathieu C, Rewers M, Steck AK, Wentworth JM, Rich SS, Kordonouri O, Ziegler AG, Herold KC; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022 Apr 1;71(4):610-623. doi: 10.2337/dbi20-0054.
- Background: PubMed 31990315Ziegler AG, Kick K, Bonifacio E, Haupt F, Hippich M, Dunstheimer D, Lang M, Laub O, Warncke K, Lange K, Assfalg R, Jolink M, Winkler C, Achenbach P; Fr1da Study Group. Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany. JAMA. 2020 Jan 28;323(4):339-351. doi: 10.1001/jama.2019.21565.
- Background: PubMed 18823409Mahon JL, Sosenko JM, Rafkin-Mervis L, Krause-Steinrauf H, Lachin JM, Thompson C, Bingley PJ, Bonifacio E, Palmer JP, Eisenbarth GS, Wolfsdorf J, Skyler JS; TrialNet Natural History Committee; Type 1 Diabetes TrialNet Study Group. The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results. Pediatr Diabetes. 2009 Apr;10(2):97-104. doi: 10.1111/j.1399-5448.2008.00464.x. Epub 2008 Sep 24.
- Background: PubMed 10078544Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes. 1999 Mar;48(3):460-8. doi: 10.2337/diabetes.48.3.460.
- Background: PubMed 21564455Hagopian WA, Erlich H, Lernmark A, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt R Jr, Blair A, Ilonen J, Krischer J, She J; TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011 Dec;12(8):733-43. doi: 10.1111/j.1399-5448.2011.00774.x. Epub 2011 May 12.
- Background: PubMed 27069865Ziegler AG, Danne T, Dunger DB, Berner R, Puff R, Kiess W, Agiostratidou G, Todd JA, Bonifacio E. Primary prevention of beta-cell autoimmunity and type 1 diabetes - The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) perspectives. Mol Metab. 2016 Feb 22;5(4):255-262. doi: 10.1016/j.molmet.2016.02.003. eCollection 2016 Apr.
- Background: PubMed 22060727Winkler C, Schober E, Ziegler AG, Holl RW. Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. Pediatr Diabetes. 2012 Jun;13(4):308-13. doi: 10.1111/j.1399-5448.2011.00829.x. Epub 2011 Nov 8.
- Background: PubMed 31180194Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 Aug 15;381(7):603-613. doi: 10.1056/NEJMoa1902226. Epub 2019 Jun 9.
- Individual participant dataSharing planned: No. Extend data available through external application process to university of Exeter
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Oram, Dr principal investigator
University of Exeter & Royal Devon University Healthcare NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes and Type 1 Diabetes Mellitus Maturity Onset, run by Royal Devon and Exeter NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of multi-islet autoantibody positive participants (time frame: through sample analysis, approx 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06006468, which also lists 28 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.