- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT02513615
Epigenetic Determinants of Peritoneal Fibrosis
Studieoversikt
Status
Forhold
Detaljert beskrivelse
There is considerable evidence that epigenetic changes in effector cells underlie the progressive nature of fibrogenic diseases. The investigators have developed an ex-vivo mesothelial cell culture system based on work by Aroeira and colleagues. Ex vivo cell cultures were treated with the DNA methyltransferase inhibitor 5-AZA for 72 hours. Overall, the investigators found that 11 of 14 patients' cells showed an increase in the E-Cad/alpha-SMA ratio with treatment to 5-AZA, indicating a return to a more epithelial-like phenotype and supporting an epigenetic mechanism of progressive fibrosis. The investigators hope to identify DNA methylation patterns associated with glucose exposure and peritoneal membrane solute transport in PD patients.
The investigators will take the peritoneal effluent from an overnight dwell from patients within one month of initiation of dialysis. The overnight effluent is centrifuged and the pellet is washed and cells are grown in DMEM medium. At confluence, cells are passaged into 2 flasks then taken for DNA and RNA. At 12 months, a second overnight peritoneal effluent sample will be obtained. The investigators will also gather demographic data (patient's age, diabetes, occurrence of peritonitis, cumulative PD prescription including total glucose exposure, use of icodextrin, and the results of a peritoneal equilibrium test carried out for clinical purposes between 3 and 12 months from the start of peritoneal dialysis). The investigators will use whole genome DNA methylation analysis to assess epigenetic changes in mesothelial cells from incident PD patients.
Studietype
Registrering (Faktiske)
Kontakter og plasseringer
Studiesteder
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Ontario
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Hamilton, Ontario, Canada, L8N 4A6
- St. Joseph's Healthcare
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Prøvetakingsmetode
Studiepopulasjon
Beskrivelse
Inclusion Criteria:
- Patients with end stage renal disease recently started on peritoneal dialysis. Patients will be over the age of 18.
Exclusion Criteria:
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Studieplan
Hvordan er studiet utformet?
Designdetaljer
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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DNA methylation pattern
Tidsramme: 12 months
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DNA methylation pattern will be measured after 12 months of glucose exposure compared with a baseline sample.
Gene expression will be measured by Genome wide methylation analysis.
In the incident patients, a within-subject analysis will be carried out between the naive and 12 month cell culture sample.
Gene expression analysis will be performed with the statistical software R and "BioConductor", a collection of tools for gene expression analysis.
Gene-level summaries from Human HT-12 BeadChip data will be generated using the widely used Bioconductor package lumi, which includes background correction, variance stabilization and normalization of expression data.
The Linear Models for Microarray Analysis (LIMMA) package of Bioconductor will be used for differential expression analysis.
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12 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
DNA methylation and solute transport
Tidsramme: 12 months
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The investigators will correlate changes in DNA methylation with solute transport measured by a peritoneal equilibrium test and peritoneal glucose exposure.
Solute transport is calculated from the dialysate to plasma creatinine ratio which is obtained from the peritoneal equilibrium test.
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12 months
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Peter J Margetts, MD PhD, McMaster University
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 14CECPDNA1006
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
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