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EPI-STORM: Cytokine Storm in Organ Donors (EPI-STORM)

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ClinicalTrials.gov Identifier: NCT03786991
Recruitment Status : Recruiting
First Posted : December 25, 2018
Last Update Posted : December 25, 2018
Sponsor:
Collaborator:
Centre de recherche du CHUS
Information provided by (Responsible Party):
Université de Sherbrooke

Brief Summary:
Liver transplant is the main treatment and also the last proposed to patients affected by end-stage liver disease. Over 70% of available livers are obtained from organ donors after neurologic death. Unfortunately, 20% of available organs for donation are considered improper and will never be transplanted. When neurologic death occurs, a reaction is generated by the immune system, the system that fights infections. This reaction release substances in the blood that could harm organs and particularly the liver.

Condition or disease Intervention/treatment
Organ Donation Liver Transplantation Other: No intervention

Detailed Description:
Severe neurological injuries such as those observed in neurologically deceased donors (i.e. brain death) trigger a massive cytokine release causing organ injury and affecting the number and quality of all transplanted organs, but particularly the liver. In recipients, elevated serum levels of TNF-α are associated with graft dysfunction. In donors, this association is unknown. Equally important, current models of graft injury fail to consider the epigenetic effects of physiological stressors that occurred in neurologically deceased donors. As an example, alterations in the expression profile of miRNA-155 have been observed in liver transplantation. The investigators hypothesize that in donors, peak plasma levels of pro-inflammatory cytokines and their associated miRNA (between consent and recovery) asTNF-a, are associated with a lower probability of liver recovery for transplantation and elevated graft dysfunction in recipients. The investigators propose a prospective cohort study with the main objective of validating the impact of organ donor proinflammatory markers. Samples will be collected at different time points in neurologically deceased candidate liver donors in 3 centres. Addressing an important need for the participants, the results will establish a physiological rational for new therapeutic targets in organ donors and the understanding of the contribution of epigenetics to liver graft function will lead to more personalized medicine approaches.

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Study Type : Observational
Estimated Enrollment : 105 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: EPI-STORM Cytokine Storm in Organ Donors: A Translational Study Linking Donor Epigenetic to Transplantation Success in Recipient
Actual Study Start Date : December 16, 2018
Estimated Primary Completion Date : April 1, 2020
Estimated Study Completion Date : April 1, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Organ donors
Organ donors after neurologic death (NDD) of 18 years old and older for whom consent to organ donation has been obtained.
Other: No intervention
No intervention

Liver Recipients
Liver recipients of 18 years old and older.
Other: No intervention
No intervention




Primary Outcome Measures :
  1. Liver transplantation success [ Time Frame: From consent to organ donation up to time of organ recovery ]
    Number of livers recovered


Secondary Outcome Measures :
  1. Plasma inflammatory level [ Time Frame: From consent to organ donation up to organ recovery (every 12 hours). ]
    Flow cytometry of a panel of cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12 p40, IL-12 p70, IL-13, IL-15, IFN gamma, IFN alpha, TNF alpha)

  2. miRNA biomarkers identification [ Time Frame: From consent to organ donation up to organ recovery (every 12 hours). ]
    miScript miRNA PCR Array Human Inflammatory Response & Autoimmunity using Qiagen kits and miRNA sequencing using Hiseq2000 Illumina platform


Biospecimen Retention:   Samples With DNA
Blood samples (including miRNA and buffy coat) will be drawn at 5 specific time points: at time of consent to organ donation, 12 hours after consent, 24 hours after consent, 48 hours after consent and at time of organ recovery.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Organ donors by neurologic death and liver recipients
Criteria

Inclusion Criteria:

  • Organ donors after neurologic death
  • Consent to organ donation
  • 18 years old and older

Exclusion Criteria:

  • S. Aureus bacteremia
  • Positive human immunodeficiency virus
  • Hepatic insufficiency defined as i) INR > 1.5, ii) hepatic encephalopathy, iii) AST, ALT > 2 times normal value
  • Hepatitis A, B or C
  • Active neoplasia
  • Receiving immunosuppressive therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03786991


Contacts
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Contact: Marie-Hélène Masse, RRT 819-346-1110 ext 14173 marie-helene.masse3@usherbrooke.ca
Contact: Marie-Claude Battista, PhD 819-346-1110 ext 12480 marie-claude.battista@usherbrooke.ca

Locations
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Canada, Quebec
Centre de recherche CHUS Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: Marie-Hélène Masse    819-346-1110 ext 14173    marie-helene.masse3@usherbrooke.ca   
CIUSSS de l'Estrie-CHUS Recruiting
Sherbrooke, Quebec, Canada, J1H5N4
Contact: Marie-Hélène Masse    819-346-1110 ext 14173    marie-helene.masse3@usherbrooke.ca   
Contact: Marie-Claude Battista, PhD    819-346-1110 ext 12480    marie-claude.battista@usherbrooke.ca   
Sponsors and Collaborators
Université de Sherbrooke
Centre de recherche du CHUS
Investigators
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Principal Investigator: Dr Frédérick D'Aragon, MD FRCPC MSc Université de Sherbrooke

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Responsible Party: Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT03786991     History of Changes
Other Study ID Numbers: MP-31-2019-2960
First Posted: December 25, 2018    Key Record Dates
Last Update Posted: December 25, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No