Hashimoto ThyroiditisTHYRODNANCT02491567
DNA Methylation and Autoimmune Thyroid Diseases
An observational study of Hashimoto Thyroiditis and Graves Disease, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to… Read more about this study
- Who is it for?
- Ages 4 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Hashimoto Thyroiditis, Graves Disease
- How many people
- 110 participants
- Where
- 1 siteGreece
- Study dates
- Sep 2014to Apr 2018
- 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 4 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Children and adolescents of Greek origin, aged 4-18 years old with a diagnosis of Hashimoto Thyroiditis and Graves Disease as well as healthy controls.
Who may be able to join
- For HT:
- A positive titers of antithyroid peroxidase (anti-TPO) or antithyroglobulin (anti-Tg) antibodies and at least one of:
- Abnormal thyroid function that requires substitution treatment with L-thyroxine (TSH > 5 μIU/ml and decreased or normal levels of fT4 or fT3)
- Increased volume of thyroid gland (goiter)
- Morphological changes on ultrasound of the thyroid gland
- For GD:
Show all 12Show fewer
- A positive titers of thyroid stimulating antibodies (anti-TSI) and
- Decreased TSH levels and increased levels of fT4 or fT3
- For Controls:
- Otherwise healthy children and adolescents, age- and gender-matched with patients
- Absence of previously known chronic disease of autoimmune aetiology or atopy (including those with a history of chronic treatment with antihistamines, anti-inflammatory, corticosteroids or anti-epileptic drugs)
- Absence of a family history of autoimmune disease in first-degree relatives
Who cannot join
- Not Caucasian origin or affinity among participants
- Age of diagnosis above 18 years
- Disease duration below 3 months
Trial locations and contacts
1 site in 1 country.
Greece1 site
Unit of Pediatric Endocrinology, Diabetes and Metabolism-4th Department of Pediatrics, Medical School of Aristotle University of Thessaloniki
Thessaloniki, 56403
About this study
Official title: Study of DNA Methylation in Children and Adolescents With Autoimmune Thyroid Diseases
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to chromatin that do not directly alter the DNA sequence. A very limited number of epigenetic studies have been published in patients with HT and GD so far. Therefore, the purpose of this study is to analyze DNA methylation status in White Blood Cells (WBCs) within the promoter regions of genomic sites that have been previously identified as susceptibility loci or sites for autoimmune thyroid disease, such as the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 genes.
Read the detailed description
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. HT involves a cell-mediated autoimmune destruction of the thyroid leading to hypothyroidism. GD is caused by a process in which immune cells make stimulating antibodies against the thyroid stimulating hormone (TSH) receptor on the thyroid gland, thus leading to hyperthyroidism. Although there is substantial evidence that genetic factors increase the risk for developing autoimmune diseases, monozygotic twins still remain discordant for disease (disease concordance is never 100%), thus suggesting a role for environmental factors and epigenetics.
Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to chromatin that do not directly alter the DNA sequence. These modifications have been associated with altered gene expression and silencing of repetitive elements and can be inherited mitotically. Epigenetic mechanisms include DNA methylation, histone modifications, or miRNA post-transcriptional regulation. DNA methylation involves the covalent addition of a methyl group to the carbon-5 position in the CpG dinucleotide from the methyl donor S-adenosylmethionine and is mediated by a group of enzymes called DNA methyltransferases (DNMTs). CpG dinucleotides are typically grouped together in regions known as CGIs (islands). CGIs can be found in the promoter regions of genes, and CpG methylation of these gene promoters is associated with transcriptional silencing. In contrast, hypermethylated genes have been found to be transcriptionally active.
A very limited number of epigenetic studies have been published in patients with HT and GD so far. Therefore, the purpose of this study is to analyze DNA methylation status in White Blood Cells (WBCs) within the promoter regions of genomic sites that have been previously identified as susceptibility loci or sites for autoimmune thyroid disease, such as the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 genes.
Initially, recruitment of patients and controls as well as blood sample collection will be done. A complete physical examination will also be performed in all participants included in the study, and a detailed personal, family, gestational and perinatal history will be obtained as well before inclusion. Blood samples by all participants will be collected and centrifuged and then White Blood Cells (WBCs), plasma and serum will be separated and stored in a deep freezer.
Laboratory analyses will follow. DNA will be isolated from peripheral leukocytes using the QIAamp DNA Blood Mini Kit, according to the manufacturer's instructions. It will then be treated with sodium bisulfite using the Zymo EZ DNA Methylation-Gold Kit, again according to the manufacturer's protocol. Therefore, unmethylated cytosines will be converted into uracyls, whereas methylated cytosines will remain unchanged. Quantification of the methylation status of DNA at the gene promoter regions under study will be made, using specific primers that detect modified DNA, by real-time PCR and analysis of the melting curves of the selected fragments of DNA. Amplicons will also be analyzed by electrophoresis and visualized by ultraviolet trans-illumination.
An electronic Data Base will be constructed and Statistical Analysis will follow. Results and Conclusions will be published in peer-review journals and presented in International Meetings.
- Conditions
- Hashimoto Thyroiditis, Graves Disease
- Medical subject headings
- Hashimoto Disease, Graves Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Hashimoto Thyroiditis (HT) | Children and adolescents with Hashimoto thyroiditis either hypothyroidic or euthyroidic. | |
| Graves Disease (GD) | Children and adolescents with Graves Disease both those on remission and under antihyroid medication. | |
| Controls (C) | Healthy individuals matched for gender and age without 1) any autoimmune disease 2) family history of autoimmune disease in the first degree relatives |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation status of CpGs within gene promoters
Percentage of DNA methylation of CpGs within the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 promoter genes in White Blood Cells (WBCs).
Measured: 1 month
Secondary outcomes (33)
Age
Age of each participant
Measured: 1 day
Age of disease onset
Age of disease diagnosis
Measured: 1 day
Sex
Male or female
Measured: 1 day
Body mass index
Weight in kg / height in m * height in m
Measured: 1 day
Pubertal stage
Prepubertal or pubertal stage
Measured: 1 day
Antibodies titre
Titre of antiTPO, antiTg, anti-TSI antibodies in blood
Measured: 1 day
Thyroid volume
Volume of the thyroid gland in total (both lobes)
Measured: 1 day
Treatment dose
Dose of Levothyroxine/thiamazole per kg of body weight /per day (if applicable)
Measured: 1 day
B12
Levels of B12 in blood
Measured: 1 day
Folic acid
Levels of folic acid in blood
Measured: 1 day
IgA, IgG, IgM, IgE immunoglobulins
Levels of IgA, IgG, IgM, IgE immunoglobulins in blood
Measured: 1 day
History of infections
Number of previous febrile viral /bacterial infections per year
Measured: 1 day
History of medications
Number of previous medications per year
Measured: 1 day
Other autoimmune diseases
Diagnosis of co-existing autoimmune disease (except autoimmune thyroid disease)
Measured: 1 day
Family history of autoimmune thyroid (or other) disease
Family history of autoimmune thyroid (or other) disease or not
Measured: 1 day
Parental educational level
Elementary school, high school or university graduate
Measured: 1 day
Type of Residence
Urban or rural residence
Measured: 1 day
Parental smoking
Total number of cigarettes per day during their child's life separately for each parent (if applicable)
Measured: 1 day
Previous births
Number of previous births
Measured: 1 day
Month of birth
Month of birth (from January to December)
Measured: 1 day
Delivery type
Cesarean section or vaginal delivery
Measured: 1 day
Birth weight
Birth weight
Measured: 1 day
Gestation duration
Duration of pregnancy
Measured: 1 day
Medications during pregnancy
Number of medications of any type received during pregnancy (if applicable)
Measured: 1 day
Maternal smoking during pregnancy
Total number of cigarettes per day during pregnancy (if applicable)
Measured: 1 day
Maternal alcohol consumption during pregnancy
Total number of glasses of alcohol consumption per day during pregnancy (if applicable)
Measured: 1 day
Pre-eclampsia (during pregnancy)
Diagnosis of pre-eclampsia (during pregnancy) or not
Measured: 1 day
Gestational diabetes (during pregnancy)
Diagnosis of gestational diabetes (during pregnancy) or not
Measured: 1 day
Vaginal bleeding (during pregnancy)
Presence of vaginal bleeding (during pregnancy) or not
Measured: 1 day
Maternal febrile infection (during pregnancy)
Diagnosis of maternal febrile infection (during pregnancy) or not
Measured: 1 day
Duration of breastfeeding
Duration of breastfeeding until discontinuance
Measured: 1 day
History of phototherapy
History of phototherapy during neonatal period (or not)
Measured: 1 day
APGAR score
APGAR score at 1st and 5th min of life
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study startSep 2014
- Primary completionSep 2016
- Study completionApr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for Hashimoto ThyroiditisStudies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Assimina Galli-Tsinopoulou, Aristotle University Of Thessaloniki
- Investigators
- Assimina Galli-Tsinopoulou, Professor, Principal investigator, Medical School, Aristotle University of Thessaloniki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491567
- Sponsor's protocol ID
- 62/17-2-2014
- Acronym
- THYRODNA
- Status last verified
- Sep 2019
- First submitted
- 23 Dec 2014
- Last updated
- 26 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM, Herold KC. Detection of beta cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19018-23. doi: 10.1073/pnas.1111008108. Epub 2011 Nov 9.
PubMed 22074781Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ, Stevens H, Todd JA, Walker NM, Rich SS; Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009 Jun;41(6):703-7. doi: 10.1038/ng.381. Epub 2009 May 10.
PubMed 19430480Cooper JD, Simmonds MJ, Walker NM, Burren O, Brand OJ, Guo H, Wallace C, Stevens H, Coleman G; Wellcome Trust Case Control Consortium; Franklyn JA, Todd JA, Gough SC. Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet. 2012 Dec 1;21(23):5202-8. doi: 10.1093/hmg/dds357. Epub 2012 Aug 24.
PubMed 22922229Dang MN, Buzzetti R, Pozzilli P. Epigenetics in autoimmune diseases with focus on type 1 diabetes. Diabetes Metab Res Rev. 2013 Jan;29(1):8-18. doi: 10.1002/dmrr.2375.
PubMed 23180441Davies TF, Latif R, Yin X. New genetic insights from autoimmune thyroid disease. J Thyroid Res. 2012;2012:623852. doi: 10.1155/2012/623852. Epub 2012 Feb 28.
PubMed 22530160Fradin D, Le Fur S, Mille C, Naoui N, Groves C, Zelenika D, McCarthy MI, Lathrop M, Bougneres P. Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes. PLoS One. 2012;7(5):e36278. doi: 10.1371/journal.pone.0036278. Epub 2012 May 2.
PubMed 22567146Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y. Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. Endocr Rev. 2008 Oct;29(6):697-725. doi: 10.1210/er.2008-0015. Epub 2008 Sep 5.
PubMed 18776148Lu Q. The critical importance of epigenetics in autoimmunity. J Autoimmun. 2013 Mar;41:1-5. doi: 10.1016/j.jaut.2013.01.010. Epub 2013 Feb 1.
PubMed 23375849MacFarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome. 2009 Sep-Oct;20(9-10):624-32. doi: 10.1007/s00335-009-9213-6. Epub 2009 Aug 22.
PubMed 19697079Quintero-Ronderos P, Montoya-Ortiz G. Epigenetics and autoimmune diseases. Autoimmune Dis. 2012;2012:593720. doi: 10.1155/2012/593720. Epub 2012 Mar 22.
PubMed 22536485Rakyan VK, Beyan H, Down TA, Hawa MI, Maslau S, Aden D, Daunay A, Busato F, Mein CA, Manfras B, Dias KR, Bell CG, Tost J, Boehm BO, Beck S, Leslie RD. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet. 2011 Sep;7(9):e1002300. doi: 10.1371/journal.pgen.1002300. Epub 2011 Sep 29.
PubMed 21980303Weetman AP. Determinants of autoimmune thyroid disease. Nat Immunol. 2001 Sep;2(9):769-70. doi: 10.1038/ni0901-769. No abstract available.
PubMed 11526381Yin X, Latif R, Tomer Y, Davies TF. Thyroid epigenetics: X chromosome inactivation in patients with autoimmune thyroid disease. Ann N Y Acad Sci. 2007 Sep;1110:193-200. doi: 10.1196/annals.1423.021.
PubMed 17911434
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of DNA Methylation in Children and Adolescents With Autoimmune Thyroid Diseases
- ClinicalTrials.gov ID
- NCT02491567
- Acronym / sponsor ID
- THYRODNA / 62/17-2-2014
- Conditions
- Hashimoto Thyroiditis, Graves Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Sep 2016 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 8 Jul 2015 (estimated)
- 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.
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to chromatin that do not directly alter the DNA sequence. A very limited number of epigenetic studies have been published in patients with HT and GD so far. Therefore, the purpose of this study is to analyze DNA methylation status in White Blood Cells (WBCs) within the promoter regions of genomic sites that have been previously identified as susceptibility loci or sites for autoimmune thyroid disease, such as the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 genes.
Detailed description
Hashimoto Thyroiditis (HT) and Graves Disease (GD) are known to be caused by abnormal immune response against self cells and tissues. HT involves a cell-mediated autoimmune destruction of the thyroid leading to hypothyroidism. GD is caused by a process in which immune cells make stimulating antibodies against the thyroid stimulating hormone (TSH) receptor on the thyroid gland, thus leading to hyperthyroidism. Although there is substantial evidence that genetic factors increase the risk for developing autoimmune diseases, monozygotic twins still remain discordant for disease (disease concordance is never 100%), thus suggesting a role for environmental factors and epigenetics.
Epigenetics is a novel field of biology studying the mechanisms by which the environment interacts with the genotype to produce a variety of phenotypes through modifications to chromatin that do not directly alter the DNA sequence. These modifications have been associated with altered gene expression and silencing of repetitive elements and can be inherited mitotically. Epigenetic mechanisms include DNA methylation, histone modifications, or miRNA post-transcriptional regulation. DNA methylation involves the covalent addition of a methyl group to the carbon-5 position in the CpG dinucleotide from the methyl donor S-adenosylmethionine and is mediated by a group of enzymes called DNA methyltransferases (DNMTs). CpG dinucleotides are typically grouped together in regions known as CGIs (islands). CGIs can be found in the promoter regions of genes, and CpG methylation of these gene promoters is associated with transcriptional silencing. In contrast, hypermethylated genes have been found to be transcriptionally active.
A very limited number of epigenetic studies have been published in patients with HT and GD so far. Therefore, the purpose of this study is to analyze DNA methylation status in White Blood Cells (WBCs) within the promoter regions of genomic sites that have been previously identified as susceptibility loci or sites for autoimmune thyroid disease, such as the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 genes.
Initially, recruitment of patients and controls as well as blood sample collection will be done. A complete physical examination will also be performed in all participants included in the study, and a detailed personal, family, gestational and perinatal history will be obtained as well before inclusion. Blood samples by all participants will be collected and centrifuged and then White Blood Cells (WBCs), plasma and serum will be separated and stored in a deep freezer.
Laboratory analyses will follow. DNA will be isolated from peripheral leukocytes using the QIAamp DNA Blood Mini Kit, according to the manufacturer's instructions. It will then be treated with sodium bisulfite using the Zymo EZ DNA Methylation-Gold Kit, again according to the manufacturer's protocol. Therefore, unmethylated cytosines will be converted into uracyls, whereas methylated cytosines will remain unchanged. Quantification of the methylation status of DNA at the gene promoter regions under study will be made, using specific primers that detect modified DNA, by real-time PCR and analysis of the melting curves of the selected fragments of DNA. Amplicons will also be analyzed by electrophoresis and visualized by ultraviolet trans-illumination.
An electronic Data Base will be constructed and Statistical Analysis will follow. Results and Conclusions will be published in peer-review journals and presented in International Meetings.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Hashimoto Thyroiditis (HT) | – | –Children and adolescents with Hashimoto thyroiditis either hypothyroidic or euthyroidic. |
| Graves Disease (GD) | – | –Children and adolescents with Graves Disease both those on remission and under antihyroid medication. |
| Controls (C) | – | –Healthy individuals matched for gender and age without 1) any autoimmune disease 2) family history of autoimmune disease in the first degree relatives |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Children and adolescents of Greek origin, aged 4-18 years old with a diagnosis of Hashimoto Thyroiditis and Graves Disease as well as healthy controls.
Key inclusion criteria (12 listed)
- A positive titers of antithyroid peroxidase (anti-TPO) or antithyroglobulin (anti-Tg) antibodies and at least one of:
- Abnormal thyroid function that requires substitution treatment with L-thyroxine (TSH > 5 μIU/ml and decreased or normal levels of fT4 or fT3)
- Increased volume of thyroid gland (goiter)
- Morphological changes on ultrasound of the thyroid gland
- A positive titers of thyroid stimulating antibodies (anti-TSI) and
Key exclusion criteria (3 listed)
- Not Caucasian origin or affinity among participants
- Age of diagnosis above 18 years
- Disease duration below 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
DNA methylation status of CpGs within gene promoters
Time frame: 1 month
Percentage of DNA methylation of CpGs within the CD40L, FOXP3, CTLA4, PTPN22, IL2RA, FCRL3 and HLADRB1 promoter genes in White Blood Cells (WBCs).
33 secondary outcomes
Age
Time frame: 1 day
Age of disease onset
Time frame: 1 day
Sex
Time frame: 1 day
Body mass index
Time frame: 1 day
Pubertal stage
Time frame: 1 day
Antibodies titre
Time frame: 1 day
Thyroid volume
Time frame: 1 day
Treatment dose
Time frame: 1 day
B12
Time frame: 1 day
Folic acid
Time frame: 1 day
IgA, IgG, IgM, IgE immunoglobulins
Time frame: 1 day
History of infections
Time frame: 1 day
History of medications
Time frame: 1 day
Other autoimmune diseases
Time frame: 1 day
Family history of autoimmune thyroid (or other) disease
Time frame: 1 day
Parental educational level
Time frame: 1 day
Type of Residence
Time frame: 1 day
Parental smoking
Time frame: 1 day
Previous births
Time frame: 1 day
Month of birth
Time frame: 1 day
Delivery type
Time frame: 1 day
Birth weight
Time frame: 1 day
Gestation duration
Time frame: 1 day
Medications during pregnancy
Time frame: 1 day
Maternal smoking during pregnancy
Time frame: 1 day
Maternal alcohol consumption during pregnancy
Time frame: 1 day
Pre-eclampsia (during pregnancy)
Time frame: 1 day
Gestational diabetes (during pregnancy)
Time frame: 1 day
Vaginal bleeding (during pregnancy)
Time frame: 1 day
Maternal febrile infection (during pregnancy)
Time frame: 1 day
Duration of breastfeeding
Time frame: 1 day
History of phototherapy
Time frame: 1 day
APGAR score
Time frame: 1 day
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 26 Sep 2019.
- Background: PubMed 22074781Akirav EM, Lebastchi J, Galvan EM, Henegariu O, Akirav M, Ablamunits V, Lizardi PM, Herold KC. Detection of beta cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):19018-23. doi: 10.1073/pnas.1111008108. Epub 2011 Nov 9.
- Background: PubMed 19430480Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, Julier C, Morahan G, Nerup J, Nierras C, Plagnol V, Pociot F, Schuilenburg H, Smyth DJ, Stevens H, Todd JA, Walker NM, Rich SS; Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009 Jun;41(6):703-7. doi: 10.1038/ng.381. Epub 2009 May 10.
- Background: PubMed 22922229Cooper JD, Simmonds MJ, Walker NM, Burren O, Brand OJ, Guo H, Wallace C, Stevens H, Coleman G; Wellcome Trust Case Control Consortium; Franklyn JA, Todd JA, Gough SC. Seven newly identified loci for autoimmune thyroid disease. Hum Mol Genet. 2012 Dec 1;21(23):5202-8. doi: 10.1093/hmg/dds357. Epub 2012 Aug 24.
- Background: PubMed 23180441Dang MN, Buzzetti R, Pozzilli P. Epigenetics in autoimmune diseases with focus on type 1 diabetes. Diabetes Metab Res Rev. 2013 Jan;29(1):8-18. doi: 10.1002/dmrr.2375.
- Background: PubMed 22530160Davies TF, Latif R, Yin X. New genetic insights from autoimmune thyroid disease. J Thyroid Res. 2012;2012:623852. doi: 10.1155/2012/623852. Epub 2012 Feb 28.
- Background: PubMed 22567146Fradin D, Le Fur S, Mille C, Naoui N, Groves C, Zelenika D, McCarthy MI, Lathrop M, Bougneres P. Association of the CpG methylation pattern of the proximal insulin gene promoter with type 1 diabetes. PLoS One. 2012;7(5):e36278. doi: 10.1371/journal.pone.0036278. Epub 2012 May 2.
- Background: PubMed 18776148Huber A, Menconi F, Corathers S, Jacobson EM, Tomer Y. Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms. Endocr Rev. 2008 Oct;29(6):697-725. doi: 10.1210/er.2008-0015. Epub 2008 Sep 5.
- Background: PubMed 23375849Lu Q. The critical importance of epigenetics in autoimmunity. J Autoimmun. 2013 Mar;41:1-5. doi: 10.1016/j.jaut.2013.01.010. Epub 2013 Feb 1.
- Background: PubMed 19697079MacFarlane AJ, Strom A, Scott FW. Epigenetics: deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome. 2009 Sep-Oct;20(9-10):624-32. doi: 10.1007/s00335-009-9213-6. Epub 2009 Aug 22.
- Background: PubMed 22536485Quintero-Ronderos P, Montoya-Ortiz G. Epigenetics and autoimmune diseases. Autoimmune Dis. 2012;2012:593720. doi: 10.1155/2012/593720. Epub 2012 Mar 22.
- Background: PubMed 21980303Rakyan VK, Beyan H, Down TA, Hawa MI, Maslau S, Aden D, Daunay A, Busato F, Mein CA, Manfras B, Dias KR, Bell CG, Tost J, Boehm BO, Beck S, Leslie RD. Identification of type 1 diabetes-associated DNA methylation variable positions that precede disease diagnosis. PLoS Genet. 2011 Sep;7(9):e1002300. doi: 10.1371/journal.pgen.1002300. Epub 2011 Sep 29.
- Background: PubMed 11526381Weetman AP. Determinants of autoimmune thyroid disease. Nat Immunol. 2001 Sep;2(9):769-70. doi: 10.1038/ni0901-769. No abstract available.
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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.
Assimina Galli-Tsinopoulou, Professor principal investigator
Medical School, Aristotle University of Thessaloniki
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 Hashimoto Thyroiditis and Graves Disease, run by Aristotle University Of Thessaloniki at 1 site in Greece.
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 12 inclusion and 3 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 26 Sep 2019. 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 Greece. 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?
DNA methylation status of CpGs within gene promoters (time frame: 1 month). 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 NCT02491567, which also lists 13 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 26 Sep 2019.