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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03786991
Recruitment Status : Recruiting
First Posted : December 26, 2018
Last Update Posted : March 25, 2020
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 : December 1, 2021
Estimated Study Completion Date : December 1, 2021

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 organ recovery (donor goes to operating room) ]
    Number of livers recovered

Secondary Outcome Measures :
  1. Plasma inflammatory level [ Time Frame: From consent to organ donation up to organ recovery (donor goes to operating room) (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 (donor goes to operating room) (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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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

Phase 1 of the study:

Inclusion Criteria:

  • Patient admitted to the intensive care unit with a serious neurologic injury
  • Glasgow Coma Scale score ≤ 4
  • Absence of sedation for the last 6 hours
  • Age ≥ 18 years old

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

Phase 2 of the study:

Inclusion Criteria:

  • Organ donor after neurologic death (DND) as presumed by the treating physician
  • Consent to organ donation

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 identifier (NCT number): NCT03786991

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Contact: Marie-Hélène Masse, RRT 819-346-1110 ext 14173
Contact: Marie-Claude Battista, PhD 819-346-1110 ext 12480

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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   
CIUSSS de l'Estrie-CHUS Recruiting
Sherbrooke, Quebec, Canada, J1H5N4
Contact: Marie-Hélène Masse    819-346-1110 ext 14173   
Contact: Marie-Claude Battista, PhD    819-346-1110 ext 12480   
Sponsors and Collaborators
Université de Sherbrooke
Centre de recherche du CHUS
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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 Identifier: NCT03786991    
Other Study ID Numbers: MP-31-2019-2960
First Posted: December 26, 2018    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: March 2020
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