Organ DonationEPI-STORMNCT03786991
EPI-STORM: Cytokine Storm in Organ Donors
An observational study of Organ Donation and Liver Transplantation, run by Université de Sherbrooke at 4 sites in Canada.
Trial summary
Kidney and liver transplantation are the treatment of choice and are often the last therapeutic option offered to patients with chronic renal and liver failure. More than 70% of kidneys and liver available for transplantation are obtained from donors following neurological death. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Organ Donation, Liver Transplantation, Kidney Transplantation
- How many people
- 105 participants
- Where
- 4 sitesCanada
- Study dates
- 16 Dec 2018to 1 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Organ donors by neurologic death and liver and kidney recipients
Who may be able to join
- Patient admitted to the intensive care unit with a serious neurologic lesion
- Glasgow Coma Scale score ≤ 4
- Absence of sedation for the last 6 hours
- Age ≥ 18 years old
- Organ donor after neurologic death (DND) declaration as determined by the attending physician
- Consent to organ donation obtained
Who cannot join
- S. aureus bacteremia
- Active neoplasia
- Receiving immunosuppressive therapy (including steroids) for > 3 months
- Specific to potential liver donors:
- Hepatic insufficiency defined as i) INR > 1.5, ii) hepatic encephalopathy, iii) AST, ALT > 2 times normal value
- Specific to potential kidney donors:
Show all 9Show fewer
- Polycystic kidney disease
- Chronic renal failure (i.e., eGFR < 60 ml/min)
- Phase 2 of the study:
Trial locations and contacts
4 sites in 1 country.
Canada4 sites, 4 recruiting
- Recruiting
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, H1T 2M4
- Recruiting
Centre Hospitalier Universitaire de Montréal
Montreal, Quebec, H2X 3E4
- Recruiting
Centre Hospitalier Universitaire de Québec- Université Laval
Québec, Quebec, G1V 4G2
- Recruiting
CIUSSS de l'Estrie-CHUS
Sherbrooke, Quebec, J1H 5N4
Marie-Hélène Masse, RRT, MSc, 819-346-1110 ext. 14173, marie-helene.masse3@usherbrooke.ca
Daphnée Lamarche, PhD, 819-821-8000 ext. 70106, daphnee.lamarche@usherbrooke.ca
About this study
Official title: EPI-STORM Cytokine Storm in Organ Donors: A Translational Study Linking Donor Epigenetic to Transplantation Success in Recipient
Kidney and liver transplantation are the treatment of choice and are often the last therapeutic option offered to patients with chronic renal and liver failure. More than 70% of kidneys and liver available for transplantation are obtained from donors following neurological death. Unfortunately, compared to living donation, transplant function, graft survival, and recipient survival are consistently inferior with kidneys and liver from neurologically deceased donors. This difference lies with the exacerbated pro-inflammatory state characteristic of deceased donors. Indeed, when neurologic death occurs, the immune system releases substances in the blood that could harm organs and particularly the liver and the kidneys. We believe that achieving a better understanding of the inflammatory processes of organ donors could be greatly informative to design future randomized controlled trial assessing the effect of personalized immunosuppressive therapy on organ donors to ultimately improve the care provided to donors so as to increase the number of organs available for transplantation and enhancing the survival of received grafts
Read the detailed description
Severe neurological injuries, such as those observed in neurologically deceased donors, trigger a pro-inflammatory state that activates the immune system, increases vascular permeability, and recruits and activates immune cells in solid organs. The rapid and intense increase in circulating pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α) following neurological death, has been referred to as the cytokine storm, one condition that is not seen among living donors. Interestingly, increased expression of TNF-α in the kidney and liver at the time of transplantation has been associated with reduced graft survival and acute rejection. Moreover, numerous studies have suggested that miRNA biomarkers can be targeted as diagnostic or therapeutic molecules in the field of organ transplantation. However, current models of graft injury fail to consider the epigenetic effects of physiological stressors that occurred in neurologically deceased donors. Although several biomarkers have been associated with graft dysfunction, the changes within the donor's inflammatory state, the mechanism underlying these events in donors, and the impacts on recipients are only poorly understood.
The investigators propose a multicenter prospective cohort study with the main objective of assessing the pro-inflammatory status of neurologically deceased donors by examining both miRNAs and circulatory cytokines and investigating its association with graft function in the recipient. Blood specimens will be collected at various time points in neurologically deceased liver and kidney donors in 5 organ recovery centres. The investigators hypothesize that in donors, Peak plasma concentration of pro-inflammatory cytokines and inflammatory-associated miRNAs targets (between consent and recovery) are associated with an increase in kidney delayed graft function and liver early graft dysfunction in the recipients. Considering that there is a therapeutic arsenal for treating donor cytokine storms( e.g., immunosuppressants) and that new targets based on a highly personalized mechanism could be developed we believe that the knowledge acquired in this research program will make it possible to improve the rate of livers and kidneys recovered from potential donors as well as enhance graft function in recipients.
- Being tested
- No intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| Organ donors | Organ donors after neurologic death (NDD) of 18 years old and older for whom consent to organ donation has been obtained. Receives: Other: No intervention | |
| Liver and kidney Recipients | Liver and kidney recipients of 18 years old and older. Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kidney delayed graft function
Requirement for renal replacement therapy within the first 7 days following transplantation or decrease of < 10% of creatinine after 3 days after transplantation, or creatinine > 250 µmol/l at day 5 with evidence of delayed graft function by renal scintigraphy
Measured: 7-days post-transplantation
Secondary outcomes (5)
Liver early graft dysfunction
Presence of one of the following three criteria: (i) peak AST or ALT > 2000 U/L during the first 7 days, (ii) bilirubin ≥ 10 mg/dL on day 7 postoperatively, or (iii) INR ≥ 1.6 on day 7 postoperatively
Measured: 7-days post-transplantation
Quantification of circulatory cytokines
Quantification of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 (p70), IL-13, IFN-γ, and TNF-α by Luminex (Multiplex human cytokine panel, Millipore)
Measured: From ICU admission up to organ recovery (5 timepoints(1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 25 donors).
Identification of inflammatory-related miRNA targets using micro-transcriptome analyses
Sequencing on an Illumina NovaSeq 6000 sequencing platform
Measured: From ICU admission up to organ recovery (5 timepoints (1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room) ;25 donors).
Validation of inflammatory-related miRNA targets using targeted quantification
Quantification by RT-qPCR using TaqMan Advanced miRNA Assays
Measured: From ICU admission up to organ recovery (5 timepoints(1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 105 donors).
Validation of circulatory cytokines
Quantification of identified cytokines (in the 25 donors cohort) by Luminex (Multiplex, Millipore)
Measured: From ICU admission up to organ recovery (5 timepoints (1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 105 donors).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2018
- Study start16 Dec 2018
- Primary completion24 Mar 2025
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Organ DonationStudies of the same condition, open and under way.
- More trials run by Université de SherbrookeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Université de Sherbrooke
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de recherche du CHUS
- Responsible party
- Sponsor
- Investigators
- Dr Frédérick D'Aragon, MD FRCPC MSc, Principal investigator, Université de Sherbrooke
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03786991
- Sponsor's protocol ID
- MP-31-2019-2960
- Acronym
- EPI-STORM
- Status last verified
- May 2024
- First submitted
- 30 Nov 2018
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Clement AA, Lamarche D, Masse MH, Legare C, Tai LH, Fleury Deland L, Battista MC, Bouchard L, D'Aragon F. Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm. Epigenetics. 2022 Nov;17(11):1546-1561. doi: 10.1080/15592294.2022.2076048. Epub 2022 May 21.
PubMed 35603508
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EPI-STORM Cytokine Storm in Organ Donors: A Translational Study Linking Donor Epigenetic to Transplantation Success in Recipient
- ClinicalTrials.gov ID
- NCT03786991
- Acronym / sponsor ID
- EPI-STORM / MP-31-2019-2960
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Université de SherbrookeUniversity, hospital or other
- Collaborators
- Centre de recherche du CHUS
- Study start
- 16 Dec 2018 (actual)
- Primary completion
- 24 Mar 2025 (actual)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 26 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Kidney and liver transplantation are the treatment of choice and are often the last therapeutic option offered to patients with chronic renal and liver failure. More than 70% of kidneys and liver available for transplantation are obtained from donors following neurological death. Unfortunately, compared to living donation, transplant function, graft survival, and recipient survival are consistently inferior with kidneys and liver from neurologically deceased donors. This difference lies with the exacerbated pro-inflammatory state characteristic of deceased donors. Indeed, when neurologic death occurs, the immune system releases substances in the blood that could harm organs and particularly the liver and the kidneys. We believe that achieving a better understanding of the inflammatory processes of organ donors could be greatly informative to design future randomized controlled trial assessing the effect of personalized immunosuppressive therapy on organ donors to ultimately improve the care provided to donors so as to increase the number of organs available for transplantation and enhancing the survival of received grafts
Detailed description
Severe neurological injuries, such as those observed in neurologically deceased donors, trigger a pro-inflammatory state that activates the immune system, increases vascular permeability, and recruits and activates immune cells in solid organs. The rapid and intense increase in circulating pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α) following neurological death, has been referred to as the cytokine storm, one condition that is not seen among living donors. Interestingly, increased expression of TNF-α in the kidney and liver at the time of transplantation has been associated with reduced graft survival and acute rejection. Moreover, numerous studies have suggested that miRNA biomarkers can be targeted as diagnostic or therapeutic molecules in the field of organ transplantation. However, current models of graft injury fail to consider the epigenetic effects of physiological stressors that occurred in neurologically deceased donors. Although several biomarkers have been associated with graft dysfunction, the changes within the donor's inflammatory state, the mechanism underlying these events in donors, and the impacts on recipients are only poorly understood.
The investigators propose a multicenter prospective cohort study with the main objective of assessing the pro-inflammatory status of neurologically deceased donors by examining both miRNAs and circulatory cytokines and investigating its association with graft function in the recipient. Blood specimens will be collected at various time points in neurologically deceased liver and kidney donors in 5 organ recovery centres. The investigators hypothesize that in donors, Peak plasma concentration of pro-inflammatory cytokines and inflammatory-associated miRNAs targets (between consent and recovery) are associated with an increase in kidney delayed graft function and liver early graft dysfunction in the recipients. Considering that there is a therapeutic arsenal for treating donor cytokine storms( e.g., immunosuppressants) and that new targets based on a highly personalized mechanism could be developed we believe that the knowledge acquired in this research program will make it possible to improve the rate of livers and kidneys recovered from potential donors as well as enhance graft function in recipients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Organ donors | – | Other: No interventionOrgan donors after neurologic death (NDD) of 18 years old and older for whom consent to organ donation has been obtained. |
| Liver and kidney Recipients | – | Other: No interventionLiver and kidney recipients of 18 years old and older. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Organ donors by neurologic death and liver and kidney recipients
Key inclusion criteria (6 listed)
- Patient admitted to the intensive care unit with a serious neurologic lesion
- Glasgow Coma Scale score ≤ 4
- Absence of sedation for the last 6 hours
- Age ≥ 18 years old
- Organ donor after neurologic death (DND) declaration as determined by the attending physician
Key exclusion criteria (9 listed)
- S. aureus bacteremia
- Active neoplasia
- Receiving immunosuppressive therapy (including steroids) for > 3 months
- Hepatic insufficiency defined as i) INR > 1.5, ii) hepatic encephalopathy, iii) AST, ALT > 2 times normal value
- Polycystic kidney disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Other | Liver and kidney Recipients, Organ donors |
Primary outcome
Kidney delayed graft function
Time frame: 7-days post-transplantation
Requirement for renal replacement therapy within the first 7 days following transplantation or decrease of < 10% of creatinine after 3 days after transplantation, or creatinine > 250 µmol/l at day 5 with evidence of delayed graft function by renal scintigraphy
5 secondary outcomes
Liver early graft dysfunction
Time frame: 7-days post-transplantation
Quantification of circulatory cytokines
Time frame: From ICU admission up to organ recovery (5 timepoints(1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 25 donors).
Identification of inflammatory-related miRNA targets using micro-transcriptome analyses
Time frame: From ICU admission up to organ recovery (5 timepoints (1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room) ;25 donors).
Validation of inflammatory-related miRNA targets using targeted quantification
Time frame: From ICU admission up to organ recovery (5 timepoints(1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 105 donors).
Validation of circulatory cytokines
Time frame: From ICU admission up to organ recovery (5 timepoints (1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 105 donors).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Derived from this study: PubMed 35603508Clement AA, Lamarche D, Masse MH, Legare C, Tai LH, Fleury Deland L, Battista MC, Bouchard L, D'Aragon F. Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm. Epigenetics. 2022 Nov;17(11):1546-1561. doi: 10.1080/15592294.2022.2076048. Epub 2022 May 21.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr Frédérick D'Aragon, MD FRCPC MSc principal investigator
Université de Sherbrooke
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Organ Donation and Liver Transplantation, run by Université de Sherbrooke at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marie-Hélène Masse, RRT, M.Sc. (819-346-1110 ext. 14173, marie-helene.masse3@usherbrooke.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Kidney delayed graft function (time frame: 7-days post-transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03786991, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2025.