Ignite Creation Date:
2024-05-05 @ 4:52 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00339781
Status:
COMPLETED
Last Update Posted:
2009-09-23
First Post:
2006-06-19
Brief Title:
Predictive and Protective Factors in the Cause of Diabetes - A Study in Twins
Sponsor:
National Institute of Environmental Health Sciences NIEHS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Predictive and Protective Factors in the Cause of Diabetes A Study in Twins
Status:
COMPLETED
Status Verified Date:
2009-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study conducted at St Bartholomews Hospital London England will determine whether cells passed from mother to offspring during pregnancy increase or decrease the childs risk of developing type 1 diabetes Previous research has shown that certain cells that can be passed from mothers to their children during pregnancy may affect the childs chance of developing other autoimmune diseases The cells from the mother may persist in the childs blood for years after birth and stimulate the childs immune system in such a way that may either increase or decrease the chance of the child developing diabetes This study will determine whether these cells are present in identical twins where only one of the twins has type 1 diabetes
Participants in the British Diabetic Twins Study in England may be eligible to participate Of each twin pair in the study one must have type 1 diabetes and the other must be free of the disease The twins mother must be alive and willing to provide a blood sample For female twins only their children must be alive and willing to provide either a blood or a buccal cell sample cheek swab
Participants undergo the following procedures
Both twins in each twin pair provide a blood sample collected on a single occasion
The mother of each twin pair provides a blood sample collected on a single occasion
Children of female twins provide a single sample from either the mouth or blood For children younger than 12 years of age a cell sample is collected from the inside of the mouth buccal using a toothbrush The child strokes the inside cheek of the mouth with the toothbrush ten times on each side spits this into a collection vial immediately rinses the mouth with water and adds this rinse to the sample collection vial Children over 12 years of age may provide either a buccal cell sample or a blood sample
Participants in the British Diabetic Twins Study in England may be eligible to participate Of each twin pair in the study one must have type 1 diabetes and the other must be free of the disease The twins mother must be alive and willing to provide a blood sample For female twins only their children must be alive and willing to provide either a blood or a buccal cell sample cheek swab
Participants undergo the following procedures
Both twins in each twin pair provide a blood sample collected on a single occasion
The mother of each twin pair provides a blood sample collected on a single occasion
Children of female twins provide a single sample from either the mouth or blood For children younger than 12 years of age a cell sample is collected from the inside of the mouth buccal using a toothbrush The child strokes the inside cheek of the mouth with the toothbrush ten times on each side spits this into a collection vial immediately rinses the mouth with water and adds this rinse to the sample collection vial Children over 12 years of age may provide either a buccal cell sample or a blood sample
Detailed Description:
Type 1 diabetes is one of several autoimmune diseases of unclear etiology in which the discordance rate between identical twins is between 30-40 even after many years of follow-up This intermediate discordance rate indicates that there are clearly genetic factors at play in susceptibility to type 1 diabetes with most genetic contribution coming from the HLA locus However this discordance rate also means that other non-genetic factors possibly environmental lead to the development of disease in only one of two genetically identical individuals No consensus exists on the nature of these putative environmental differences which are all the more remarkable for occurring in twins that generally share the same intrauterine family and school environment
Recent evidence has suggested that the development of certain autoimmune diseases particularly scleroderma may be influenced by microchimerism Both fetomaternal microchimerisms persistence of fetal cells in the maternal circulation after birth of the child and maternofetal microchimerism persistence of maternal cells in the childs circulation for years after birth have been suggested as creating an abnormal environment that might stimulate the development of autoimmunity in genetically susceptible individuals The reverse is also possible ie that these abnormal cells may stimulate the immune system in such a way that autoimmunity does not develop
Identical or monozygotic MZ twins who are discordant for type 1 diabetes offer a unique experimental model in which to test the hypothesis that quantitative differences in persistent maternofetal microchimerism influence the development of type 1 diabetes in these genetically susceptible individuals This study will use pairs of MZ twins discordant for the type 1 diabetes that are already participating in the British Diabetic Twins Study being conducted by Dr David Leslie at St Bartholomews Hospital in London UK If the mothers of the twins both female and male and offspring of the female twins only are available for study they will be asked to provide a single blood sample twins mothers offspring greater than 12 years of age or buccal cell sample offspring less than or equal to 12 years of age from which DNA will be purified This is to confirm the origin of the chimeric cells since cells are passed from the mothers to the offspring during pregnancy we require DNA samples from the mothers of all twins male and female who participate in this study But since the opposite is true that cells can also be passed from offspring to their mothers during pregnancy we will require DNA samples from the female twins offspring to determine the true origin of any chimeric cells The DNA will be used for HLA genotyping to identify nonshared HLA alleles that can be used to develop specific assays for the persistence of maternal DNA in the twins circulation and quantitative PCR of the mothers genotype in CD3 cells isolated from the twins Since trafficking of chimeric cells can be bi-directional twins who have had offspring of their own may have chimeric cells of both fetal and maternal origin in their circulation To confirm the origin of the chimeric cells the blood or buccal cells collected from the offspring of the twins will be genotyped and these compared to the genotypes of the twins mothers Blood will be drawn and DNA purified by Dr Leslies group in London the genotyping and quantitative PCR will be performed by Dr Artletts group at Thomas Jefferson University Philadelphia which has been studying microchimerism since 1998 Results of the study may provide evidence in support of microchimerism as an influential factor in the development of type 1 diabetes Evidence in support to this concept would be an important addition to the literature on environmental factors that influence type 1 diabetes etiology and also suggest potential immunosuppression or other strategies in type 1 diabetes prevention
Recent evidence has suggested that the development of certain autoimmune diseases particularly scleroderma may be influenced by microchimerism Both fetomaternal microchimerisms persistence of fetal cells in the maternal circulation after birth of the child and maternofetal microchimerism persistence of maternal cells in the childs circulation for years after birth have been suggested as creating an abnormal environment that might stimulate the development of autoimmunity in genetically susceptible individuals The reverse is also possible ie that these abnormal cells may stimulate the immune system in such a way that autoimmunity does not develop
Identical or monozygotic MZ twins who are discordant for type 1 diabetes offer a unique experimental model in which to test the hypothesis that quantitative differences in persistent maternofetal microchimerism influence the development of type 1 diabetes in these genetically susceptible individuals This study will use pairs of MZ twins discordant for the type 1 diabetes that are already participating in the British Diabetic Twins Study being conducted by Dr David Leslie at St Bartholomews Hospital in London UK If the mothers of the twins both female and male and offspring of the female twins only are available for study they will be asked to provide a single blood sample twins mothers offspring greater than 12 years of age or buccal cell sample offspring less than or equal to 12 years of age from which DNA will be purified This is to confirm the origin of the chimeric cells since cells are passed from the mothers to the offspring during pregnancy we require DNA samples from the mothers of all twins male and female who participate in this study But since the opposite is true that cells can also be passed from offspring to their mothers during pregnancy we will require DNA samples from the female twins offspring to determine the true origin of any chimeric cells The DNA will be used for HLA genotyping to identify nonshared HLA alleles that can be used to develop specific assays for the persistence of maternal DNA in the twins circulation and quantitative PCR of the mothers genotype in CD3 cells isolated from the twins Since trafficking of chimeric cells can be bi-directional twins who have had offspring of their own may have chimeric cells of both fetal and maternal origin in their circulation To confirm the origin of the chimeric cells the blood or buccal cells collected from the offspring of the twins will be genotyped and these compared to the genotypes of the twins mothers Blood will be drawn and DNA purified by Dr Leslies group in London the genotyping and quantitative PCR will be performed by Dr Artletts group at Thomas Jefferson University Philadelphia which has been studying microchimerism since 1998 Results of the study may provide evidence in support of microchimerism as an influential factor in the development of type 1 diabetes Evidence in support to this concept would be an important addition to the literature on environmental factors that influence type 1 diabetes etiology and also suggest potential immunosuppression or other strategies in type 1 diabetes prevention
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-E-N109 | None | None | None |