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Epigenetic Determinants of Peritoneal Fibrosis

3. marts 2020 opdateret af: Peter Margetts, McMaster University
Peritoneal dialysis (PD) is a type of kidney replacement therapy for patients with chronic kidney disease where the peritoneal membrane is used to filter the blood. Exposure to PD fluid results in scarring of the peritoneal membrane and increased blood vessel growth. This condition can progress even when peritoneal dialysis is stopped. Therefore, the investigators hypothesize glucose in the dialysis fluid may result in DNA modifications called epigenetic changes. These changes modify how genes are expressed and how cells function. The investigators want to study these epigenetic changes and the effect on peritoneal membrane scarring, blood vessel growth and peritoneal membrane function.

Studieoversigt

Status

Afsluttet

Betingelser

Detaljeret 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.

Undersøgelsestype

Observationel

Tilmelding (Faktiske)

58

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • St. Joseph's Healthcare

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

Patients with end stage renal disease recently started on peritoneal dialysis. Patients will be over the age of 18.

Beskrivelse

Inclusion Criteria:

  • Patients with end stage renal disease recently started on peritoneal dialysis. Patients will be over the age of 18.

Exclusion Criteria:

-

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
DNA methylation pattern
Tidsramme: 12 months
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.
12 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
DNA methylation and solute transport
Tidsramme: 12 months
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.
12 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

McMaster University

Efterforskere

  • Ledende efterforsker: Peter J Margetts, MD PhD, McMaster University

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. september 2015

Primær færdiggørelse (Faktiske)

1. december 2018

Studieafslutning (Faktiske)

1. december 2018

Datoer for studieregistrering

Først indsendt

30. juli 2015

Først indsendt, der opfyldte QC-kriterier

30. juli 2015

Først opslået (Skøn)

31. juli 2015

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. marts 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. marts 2020

Sidst verificeret

1. marts 2020

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 14CECPDNA1006

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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