Type 1 Diabetes MellitusMETHYLDIABNCT04139369
Methylation of DNA in Children and Adolescents With Type 1 Diabetes Mellitus (METHYLDIAB)
An observational study of Type 1 Diabetes Mellitus, run by Aristotle University Of Thessaloniki at 1 site in Greece.
Trial summary
Type 1 Diabetes Mellitus (T1DM) is a well-studied autoimmune disease resulting in insulin deficiency due to selective β-cell destruction. Epigenetics is a novel field of biology studying the inherited changes in deoxyribonucleic acid (DNA) expression which cannot be attributed to base sequence alteration. Read more about this study
- Who is it for?
- Ages 2 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes Mellitus
- How many people
- 40 participants
- Where
- 1 siteGreece
- Study dates
- May 2012to Aug 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 2 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Children and adolescents of Greek origin, aged 2-18 years old with a diagnosis of Type 1 Diabetes Mellitus as well as healthy controls age and gender matched.
Who may be able to join
- no history of T1DM or other autoimmune disease of their first degree relatives
- Greek origin (at least for 3 generations back to be Greek)
- sign written consent form
- males and females 2-18 years of age, with the diagnosis of T1DM
- T1DM diagnosis according to the criteria of International Society for Pediatric and Adolescent Diabetes (ISPAD) and ADA (American Diabetes Association)
- healthy males and females 2-18 years of age, with no consaguinity with the patients
Who cannot join
None listed.
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 Type 1 Diabetes Mellitus
Type 1 Diabetes Mellitus (T1DM) is a well-studied autoimmune disease resulting in insulin deficiency due to selective β-cell destruction. Epigenetics is a novel field of biology studying the inherited changes in deoxyribonucleic acid (DNA) expression which cannot be attributed to base sequence alteration. A relatively limited number of studies are published until now concerning T1DM in children and adolescents addressing epigenetics changes in DNA expression. The purpose of the present study is to analyze the methylation status of DNA within the promoter region of specific susceptibility genes such as Protein tyrosine phosphatase, non-receptor type 22 (PTPN-22), Insulin (INS) and Human leukocyte antigen G (HLA-G) genes.
Read the detailed description
Type 1 Diabetes Mellitus (T1DM) is a well-studied autoimmune disease resulting in insulin deficiency due to selective β-cell loss. Environmental and genetics factors seem to have a complex interplay in genetically susceptible individuals leading to T1DM development.
Epigenetics is a new field of biology studying the inherited changes in deoxyribonucleic acid (DNA) expression which cannot be attributed to DNA sequence alteration via DNA methylation, histone modification, and micro-RNAs acting as post-transcriptional regulators.
The methylation of cytosine - guanosine dinucleotides (CpGs), located at the promoter region of the genes, play a vital role in transcription and gene expression and is catalyzed at the 5' cytosine position via enzymes called DNA methyltransferases (DNMTs).
A limited number of studies regarding epigenetics in T1DM paediatric patients have been published so far. The purpose of the present study is to investigate the CpG islet methylation pattern in the promoter regions of specific susceptibility genes such as Protein tyrosine phosphatase, non-receptor type 22 (PTPN-22), Insulin (INS) and Human leukocyte antigen G (HLA-G) genes, extracted from White Blood Cells (WBCs) from T1DM and healthy controls children and adolescents .
Twenty patients and twenty age and gender matched controls were recruited. A detailed personal, family, gestational/perinatal history was obtained and a thorough physical examination was performed in all study participants. Both groups and their first grade relatives had no history of other autoimmune diseases.
Parents provided written informed consent for the participation of their children, according to the declaration of Helsinki for research. involving human subjects .
Protocols were approved by Bioethics Committee of School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece (Protocol No 185/30.12.2015).
Whole blood samples were collected from both groups after a 12-hour period of fast and stored immediately at -80 oC.
DNA was extracted from blood samples using the DNA extraction kit QIAamp® DNA Blood Mini Kit (QIAGEN Inc, CA, USA), as suggested by the manufacturer. Isolated samples were quantified spectrophotometrically using the odds ratio (OD ratio) 260/280 (1 OD = 50 μg/ml), (BioPhotometer 6131 Eppendorf AG, Germany). Bisulfite-treatment was conducted on 300ng DNA of each sample by using the EZ DNA Methylation-Gold kit (Zymo Research, Methylation-Gold, USA), as recommended by the manufacturer. Treatment with sodium bisulphate converts unmethylated cytosines into uracils, whereas methylated cytosines remain unchanged under the same stable conditions.
For INS gene promoter amplification, gene-specific primers were used as follows: INS-Forward 5'-TATTTTGGAATTTTGAGTTTATT-3'and INS-Reverse 5'-AACAAAAATCTAAAAACAACAA-3', for PTPN-22-Forward 5'-TTTTGGTTTATGTTGTAGAGT -3΄ and PTPN-22 Reverse 5΄- ATTTTATTTTATTATTTATATGTAA-3' and for HLA-G- Forward 5'-TAGGGAGTTTAGTTTAGGGAT -3' and Reverse 5'- TTAAGGATGGTGGTTATGG -3'.
Additional, overhang adapter sequence was added to the locus-specific primers for the regions to be targeted (Nextera Transposase Adaptors, Illumina), in order of prompt construction of Next Generation Sequencing (NGS) libraries. Polymerase Chain Reaction (PCR) products were amplified on a low temperature ramping instrument, the 9700 thermal cycler (Eppendorf AG No5341, 9600 emulation mode) using the AmpliTaq Gold DNA Polymerase.
After purification of PCR products with highly reactive super magnetic beads NucleoMag NGS Clean-up and Size Select (Macherey-Nagel. Cat. Number 744970.5.), they were pooled at similar molar quantities and submitted for library construction according to manufacturer instructions, Nextera XT DNA Library Preparation kit, Research Illumina.
For NGS paired-end reads were selected at 2 x 250 base pair read length formation, on a platform Illumina's MiSeq.
Sequence analysis reads were carried out using FASTQ files and methylation status was estimated with the tool ampliMethProfiler, a python-based pipeline for targeted deep bisulfite sequenced amplicons.The methylation status was analyzed at ten CpG sites of INS gene promoter, four CpG sites of PTPN-22 gene and nineteen CpG sites of HLA-G gene around the transcriptional start site (TSS).
The sequences and the identification of the methylated and unmethylated sites will be interpreted by bioinformatics scientists.
A Data-Base will be created and all the data will undergo statistical analysis.The results and the conclusions of the present study will be published in peer- review journals and presented in National and International Meetings.
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- INS gene, methylation, next generation sequencing
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Insulin-Dependent, 2
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 |
|---|---|---|
| Type 1 Diabetes Mellitus (T1DM) | Type 1 Diabetes Mellitus (T1DM) Children and adolescents with Type 1 Diabetes Mellitus | |
| Controls (C) | Controls (C) Healthy individuals matched for gender and age without any autoimmune disease of their own or their first degree relatives |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall mean methylation percentage (%) of CpGs cytosine-guanosine islands within the promoter regions of INS, PTPN-22,HLA-G genes between T1DM and healthy children and adolescents
Calculation of the overall mean methylation percentage (%) of 10 cytosine-guanosine islands (CpGs) around the Transcription Start Site (TSS) of the INS gene promoter region, of 4 CpGs of PTPN-22 gene and of 19 CpG sites of HLA-G gene respectively between T1DM and control group
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study startMay 2012
- Primary completionMay 2015
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- 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
- 40 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, MD,PhD, Principal investigator, Unit of Pediatric Endocrinology/Diabetes/Metabolism 4thDepartment of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04139369
- Sponsor's protocol ID
- PEDIATRIC DIABETOLOGY
- Acronym
- METHYLDIAB
- Status last verified
- Oct 2019
- First submitted
- 9 Jan 2016
- Last updated
- 25 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Liu L, Li Y, Tollefsbol TO. Gene-environment interactions and epigenetic basis of human diseases. Curr Issues Mol Biol. 2008;10(1-2):25-36.
PubMed 18525104Dang 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 23180441Barrett 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 22922229Lu 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 23375849Quintero-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 21980303Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7. doi: 10.1073/pnas.0510310103. Epub 2006 Jan 23.
PubMed 16432200Fradin 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 22567146Grada A, Weinbrecht K. Next-generation sequencing: methodology and application. J Invest Dermatol. 2013 Aug;133(8):e11. doi: 10.1038/jid.2013.248. No abstract available.
PubMed 23856935Behjati S, Tarpey PS. What is next generation sequencing? Arch Dis Child Educ Pract Ed. 2013 Dec;98(6):236-8. doi: 10.1136/archdischild-2013-304340. Epub 2013 Aug 28.
PubMed 23986538Fisher MM, Watkins RA, Blum J, Evans-Molina C, Chalasani N, DiMeglio LA, Mather KJ, Tersey SA, Mirmira RG. Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New-Onset Type 1 Diabetes. Diabetes. 2015 Nov;64(11):3867-72. doi: 10.2337/db15-0430. Epub 2015 Jul 27.
PubMed 26216854Lehmann-Werman R, Neiman D, Zemmour H, Moss J, Magenheim J, Vaknin-Dembinsky A, Rubertsson S, Nellgard B, Blennow K, Zetterberg H, Spalding K, Haller MJ, Wasserfall CH, Schatz DA, Greenbaum CJ, Dorrell C, Grompe M, Zick A, Hubert A, Maoz M, Fendrich V, Bartsch DK, Golan T, Ben Sasson SA, Zamir G, Razin A, Cedar H, Shapiro AM, Glaser B, Shemer R, Dor Y. Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):E1826-34. doi: 10.1073/pnas.1519286113. Epub 2016 Mar 14.
PubMed 26976580World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191-4. doi: 10.1001/jama.2013.281053. No abstract available.
PubMed 24141714Fisher MM, Perez Chumbiauca CN, Mather KJ, Mirmira RG, Tersey SA. Detection of islet beta-cell death in vivo by multiplex PCR analysis of differentially methylated DNA. Endocrinology. 2013 Sep;154(9):3476-81. doi: 10.1210/en.2013-1223. Epub 2013 Jul 3.
PubMed 23825129
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 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 Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT04139369
- Acronym / sponsor ID
- METHYLDIAB / PEDIATRIC DIABETOLOGY
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- INS gene, methylation, next generation sequencing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- May 2012 (actual)
- Primary completion
- May 2015 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 25 Oct 2019 (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.
Type 1 Diabetes Mellitus (T1DM) is a well-studied autoimmune disease resulting in insulin deficiency due to selective β-cell destruction. Epigenetics is a novel field of biology studying the inherited changes in deoxyribonucleic acid (DNA) expression which cannot be attributed to base sequence alteration. A relatively limited number of studies are published until now concerning T1DM in children and adolescents addressing epigenetics changes in DNA expression. The purpose of the present study is to analyze the methylation status of DNA within the promoter region of specific susceptibility genes such as Protein tyrosine phosphatase, non-receptor type 22 (PTPN-22), Insulin (INS) and Human leukocyte antigen G (HLA-G) genes.
Detailed description
Type 1 Diabetes Mellitus (T1DM) is a well-studied autoimmune disease resulting in insulin deficiency due to selective β-cell loss. Environmental and genetics factors seem to have a complex interplay in genetically susceptible individuals leading to T1DM development.
Epigenetics is a new field of biology studying the inherited changes in deoxyribonucleic acid (DNA) expression which cannot be attributed to DNA sequence alteration via DNA methylation, histone modification, and micro-RNAs acting as post-transcriptional regulators.
The methylation of cytosine - guanosine dinucleotides (CpGs), located at the promoter region of the genes, play a vital role in transcription and gene expression and is catalyzed at the 5' cytosine position via enzymes called DNA methyltransferases (DNMTs).
A limited number of studies regarding epigenetics in T1DM paediatric patients have been published so far. The purpose of the present study is to investigate the CpG islet methylation pattern in the promoter regions of specific susceptibility genes such as Protein tyrosine phosphatase, non-receptor type 22 (PTPN-22), Insulin (INS) and Human leukocyte antigen G (HLA-G) genes, extracted from White Blood Cells (WBCs) from T1DM and healthy controls children and adolescents .
Twenty patients and twenty age and gender matched controls were recruited. A detailed personal, family, gestational/perinatal history was obtained and a thorough physical examination was performed in all study participants. Both groups and their first grade relatives had no history of other autoimmune diseases.
Parents provided written informed consent for the participation of their children, according to the declaration of Helsinki for research. involving human subjects .
Protocols were approved by Bioethics Committee of School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece (Protocol No 185/30.12.2015).
Whole blood samples were collected from both groups after a 12-hour period of fast and stored immediately at -80 oC.
DNA was extracted from blood samples using the DNA extraction kit QIAamp® DNA Blood Mini Kit (QIAGEN Inc, CA, USA), as suggested by the manufacturer. Isolated samples were quantified spectrophotometrically using the odds ratio (OD ratio) 260/280 (1 OD = 50 μg/ml), (BioPhotometer 6131 Eppendorf AG, Germany). Bisulfite-treatment was conducted on 300ng DNA of each sample by using the EZ DNA Methylation-Gold kit (Zymo Research, Methylation-Gold, USA), as recommended by the manufacturer. Treatment with sodium bisulphate converts unmethylated cytosines into uracils, whereas methylated cytosines remain unchanged under the same stable conditions.
For INS gene promoter amplification, gene-specific primers were used as follows: INS-Forward 5'-TATTTTGGAATTTTGAGTTTATT-3'and INS-Reverse 5'-AACAAAAATCTAAAAACAACAA-3', for PTPN-22-Forward 5'-TTTTGGTTTATGTTGTAGAGT -3΄ and PTPN-22 Reverse 5΄- ATTTTATTTTATTATTTATATGTAA-3' and for HLA-G- Forward 5'-TAGGGAGTTTAGTTTAGGGAT -3' and Reverse 5'- TTAAGGATGGTGGTTATGG -3'.
Additional, overhang adapter sequence was added to the locus-specific primers for the regions to be targeted (Nextera Transposase Adaptors, Illumina), in order of prompt construction of Next Generation Sequencing (NGS) libraries. Polymerase Chain Reaction (PCR) products were amplified on a low temperature ramping instrument, the 9700 thermal cycler (Eppendorf AG No5341, 9600 emulation mode) using the AmpliTaq Gold DNA Polymerase.
After purification of PCR products with highly reactive super magnetic beads NucleoMag NGS Clean-up and Size Select (Macherey-Nagel. Cat. Number 744970.5.), they were pooled at similar molar quantities and submitted for library construction according to manufacturer instructions, Nextera XT DNA Library Preparation kit, Research Illumina.
For NGS paired-end reads were selected at 2 x 250 base pair read length formation, on a platform Illumina's MiSeq.
Sequence analysis reads were carried out using FASTQ files and methylation status was estimated with the tool ampliMethProfiler, a python-based pipeline for targeted deep bisulfite sequenced amplicons.The methylation status was analyzed at ten CpG sites of INS gene promoter, four CpG sites of PTPN-22 gene and nineteen CpG sites of HLA-G gene around the transcriptional start site (TSS).
The sequences and the identification of the methylated and unmethylated sites will be interpreted by bioinformatics scientists.
A Data-Base will be created and all the data will undergo statistical analysis.The results and the conclusions of the present study will be published in peer- review journals and presented in National and International Meetings.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 1 Diabetes Mellitus (T1DM) | – | –Type 1 Diabetes Mellitus (T1DM) Children and adolescents with Type 1 Diabetes Mellitus |
| Controls (C) | – | –Controls (C) Healthy individuals matched for gender and age without any autoimmune disease of their own or their first degree relatives |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Children and adolescents of Greek origin, aged 2-18 years old with a diagnosis of Type 1 Diabetes Mellitus as well as healthy controls age and gender matched.
Key inclusion criteria (6 listed)
- no history of T1DM or other autoimmune disease of their first degree relatives
- Greek origin (at least for 3 generations back to be Greek)
- sign written consent form
- males and females 2-18 years of age, with the diagnosis of T1DM
- T1DM diagnosis according to the criteria of International Society for Pediatric and Adolescent Diabetes (ISPAD) and ADA (American Diabetes Association)
Key exclusion criteria (0 listed)
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
Overall mean methylation percentage (%) of CpGs cytosine-guanosine islands within the promoter regions of INS, PTPN-22,HLA-G genes between T1DM and healthy children and adolescents
Time frame: 5 years
Calculation of the overall mean methylation percentage (%) of 10 cytosine-guanosine islands (CpGs) around the Transcription Start Site (TSS) of the INS gene promoter region, of 4 CpGs of PTPN-22 gene and of 19 CpG sites of HLA-G gene respectively between T1DM and control group
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 25 Oct 2019.
- Background: PubMed 18525104Liu L, Li Y, Tollefsbol TO. Gene-environment interactions and epigenetic basis of human diseases. Curr Issues Mol Biol. 2008;10(1-2):25-36.
- 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 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 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 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 16432200Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7. doi: 10.1073/pnas.0510310103. Epub 2006 Jan 23.
- 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 23856935Grada A, Weinbrecht K. Next-generation sequencing: methodology and application. J Invest Dermatol. 2013 Aug;133(8):e11. doi: 10.1038/jid.2013.248. No abstract available.
- Background: PubMed 23986538Behjati S, Tarpey PS. What is next generation sequencing? Arch Dis Child Educ Pract Ed. 2013 Dec;98(6):236-8. doi: 10.1136/archdischild-2013-304340. Epub 2013 Aug 28.
- Background: PubMed 26216854Fisher MM, Watkins RA, Blum J, Evans-Molina C, Chalasani N, DiMeglio LA, Mather KJ, Tersey SA, Mirmira RG. Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New-Onset Type 1 Diabetes. Diabetes. 2015 Nov;64(11):3867-72. doi: 10.2337/db15-0430. Epub 2015 Jul 27.
- Individual participant dataSharing planned: No
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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, MD,PhD principal investigator
Unit of Pediatric Endocrinology/Diabetes/Metabolism 4thDepartment of Pediatrics
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 Mellitus, 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 6 inclusion and 0 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 25 Oct 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?
Overall mean methylation percentage (%) of CpGs cytosine-guanosine islands within the promoter regions of INS, PTPN-22,HLA-G genes between T1DM and healthy children and adolescents (time frame: 5 years). 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 NCT04139369, which also lists 15 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 25 Oct 2019.