MicroRNA ProfileNCT06611046
MicroRNA Profile As a Biomarker of Liver Damage in Different Types of Liver Donors.
An observational study of MicroRNA Profile and Liver Transplant, run by Mar Dalmau at 1 site in Spain.
Trial summary
The goal of this observational study is to analyze the expression of liver-derived miRNAs in different types of liver donors to gain in depth knowledge about distinctive physiologic features within donors and find potential biomarkers for graft quality assessment. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- MicroRNA Profile, Liver Transplant, Organ Donor
- What is being tested?
- organ donor
- How many people
- 28 participants
- Where
- 1 siteSpain
- Study dates
- 2 Oct 2019to 1 Sep 2024
- How long will I take part?
- 3 Years
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Fourteen combined perfusates, liver biopsies and serum samples were collected prospectively from brain death donors (DBD, n=14) and donors after circulatory death (DCD, n=14). Three combined perfusates, liver biopsies and serum samples were collected prospectively from brain death donors discarded for transplantation due to significant steatosis (DBDd, n=3). Seven serum samples were collected prospectively from healthy controls undergoing elective cholecystectomy (Control, n=7). Single centre study with samples collected at Vall d'Hebron University Hospital, Spain, between October 2019 and May 2021.
Who may be able to join
- Adult deceased liver donors
- Unusable grafts for transplantation due to moderate (30% to 60%) or severe (more than 60%) steatosis in liver biopsies.
- Same inclusion criteria as the living liver donor program in our center: 18 to 60 years old, normal liver function, ultrasound without signs of liver disease and steatosis less than 30%.
Who cannot join
- Pediatric donors (less than18 year-old)
- Donors for re-transplantation cases
- Donors who underwent split or partition liver technique to obtain two small grafts for two recipients (adult and pediatric).
- Discarded DBD grafts:
- Unusable grafts discarded for other reasons.
- Pediatric donors (less than18 year-old)
Show all 10Show fewer
- Donors for re-transplantation cases
- Donors who underwent split or partition liver technique to obtain two small grafts for two recipients (adult and pediatric).
- Control group:
- Patients with preoperative deranged liver function tests.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Perfil De MicroRNA Como Biomarcador De Daño Hepático En Diferentes Tipos De Donantes De Hígado (MicroRNA Profile As a Biomarker of Liver Damage in Different Types of Liver Donors).
The goal of this observational study is to analyze the expression of liver-derived miRNAs in different types of liver donors to gain in depth knowledge about distinctive physiologic features within donors and find potential biomarkers for graft quality assessment. The main questions it aims to answer are:
Is there a distinctive miRNA profile between donors after brain-stem death and donors after circulatory death?
Read more
Is heparinase I treatment necessary to overcome miRNA quantification interference in heparinized liver donor samples ?
Researchers will compare miRNA expression in donors after brain-stem death and donors after circulatory death with I) a subgroup of donors with unusable grafts due to significant steatosis, 2) and with a subgroup of healthy controls undergoing elective cholecystectomy to set the reference miRNA profiles in extreme conditions.
Read the detailed description
Between October 2019 and May 2021, perfusates, liver biopsies and serum samples were collected prospectively from adult deceased organ donors in Vall d\'Hebron University Hospital, Barcelona, Spain.
Samples from adult human brain death donors (n=10) and donors after circulatory death (n=10) were analyzed for the presence of miR-122, miR-148, miR-155, miR-22, miR-222 and ratio miR122/miR222, target biomarkers of liver injury selected from the literature.
To set the reference miRNA profiles, a subgroup of donors with unusable grafts due to significant steatosis (n=3) were analyzed.
Donors for re-transplantation, pediatric, and split were excluded to avoid biopsy-related injury.
As there were no living donor inclusions in the study period, serum specimens from a subgroup of healthy controls undergoing elective cholecystectomy (n=7) were analyzed.
This study is part of a PhD thesis and data collection was done by the main investigator based in organ donor availability in one tertiary hospital centre in Barcelona, Spain. Based on resource limitation constraints, the sample size was limited to the consecutive samples obtained in a 2-year period.
Written informed consent was obtained from patients and relatives of donors included in the study. Samples and data from patients were provided by the Vall d'Hebron University Hospital Biobank (PT20/00107), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures. The study protocol was approved by the medical ethics committee of the Vall d'Hebron University Hospital [PR(AG)46/2019] and conforms to the principles outlined in the Declaration of Helsinki.
Statistical analysis:
To optimize the quality of data, readings with extreme Ct values (Ct less than 11 or Ct greater than 39) were discarded. The mean of the Cts and the standard deviation for each of the miRNAs in the different samples analyzed (technical triplicates) were calculated. To improve the quality of the data analyzed, in triplicates with high standard deviation (Ct SD greater than 0.3), the Ct value furthest from the mean was eliminated, leaving a total of at least two values per miRNA per sample. Likewise, for each miRNA, samples with less than two valid replicates were excluded. To correct for potential RNA input or RT efficiency biases, Ct values were normalized using the average Ct of endogenous references (miR-103a, miR-191, miR-30c, miR-16 and let7a). miRNA relative quantification (RQ) levels were analyzed using the Livak et al. method 2^(-ΔΔCt), calculated as follows ΔCt (miRNA Ct target - averaged endogenous control Ct) and the difference (ΔΔCt) between comparison groups (ΔCt comparison - ΔCt reference sample. Group comparisons were performed using T-test or U-Mann Whitney (non-parametric) for continuous data and Fisher test for qualitative. P-values less than 0.05 were considered significant.
Methodology substudy:
A subgroup of adult human brain death donors (n=4) and donors after circulatory death (n=4) were analyzed for the presence of miR-122 and miR-148. Heparin is known to have an inhibiting effect in RNA qPCR analysis and liver donor samples are prone to have heparin traces, as it\'s used to avoid thrombus formation during organ procurement. Heparinase-I has been used in the literature to overcome the heparin inhibiting effect.
In this substudy, the samples were treated with 0 IU, 6 IU or 12 IU of heparinase-I to evaluate the counteracting effect of heparinase I on miRNA detection levels by RT-qPCR.
- Conditions
- MicroRNA Profile, Liver Transplant, Organ Donor
- Being tested
- organ donor
- Keywords
- microRNA, Liver donors, Liver transplant, heparinase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
organ donorOther
Observational study with sample collection of serum, liver tissue and perfusate fluid from liver donors. No specific interventions were done to the donors as part of the study. The samples were analyzed for specific microNA expression by RT-qPCR.
*Control group: only serum samples were collected from this group.
| Study group | Role | What they receive |
|---|---|---|
| Death brain donors (DBD) | Liver grafts from brain death donors suffer systemic haemodynamic, inflammatory and endocrine changes during donor maintenance due to brain-stem activity cessation. Receives: Other: organ donor | |
| Donors after circulatory death (DCD) | Circulatory death donors do not suffer the physiologic features from brain death, almost mirroring a living donation. However, after withdrawal of life-sustaining measures these grafts suffer injury from severe ischemia. Receives: Other: organ donor | |
| Discarded DBD (dDBD) | Liver grafts from brain death donors that were unusable due to moderate to severe steatosis. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary non-function, early allograft dysfunction and post-transplant vascular and biliary complications Receives: Other: organ donor | |
| Control group | Serum samples from healthy patients who underwent elective cholecystectomy due to symptomatic gallstones were collected before incision. The patients included shared similar characteristics according to the centre living liver donor policy: 18 to 60-year-old, normal liver function and no steatosis in ultrasound. Receives: Other: organ donor |
What is being measured
The primary outcome is the main question the study is designed to answer.
miRNA expression profile in different types of liver donors.
Compare the miRNA expression profile (miR-122 and miR-148a, miR-222, miR-22 and miR-155) from death brain donors and circulatory death donors in liver biopsies, serum and perfusion solution
Measured: Data collection from regional donors in a period of two years based on donor availability and main investigator (data collector) availability. The samples were collected during organ procurement which entails over 4 to 6 hours in each donor.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2024
- Study start2 Oct 2019
- Primary completion27 Jul 2021
- Study completion1 Sep 2024
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 MicroRNA ProfileStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
- Target duration
- 3 Years
Sponsor and investigators
- Lead sponsor
- Mar Dalmau
- Sponsor type
- University, hospital or other
- Collaborators
- Vall Hebron Insitut Recerca
- Responsible party
- Sponsor-investigator, Mar Dalmau, Hospital Vall d'Hebron
- Investigators
- Ramon Charco, MD, PhD, Study director, Chief of HPB surgery and Transplant Department in Vall d Hebron University HospitalConcepción Gómez-Gavara, MD, PhD, Study director, HPB surgery and Liver Transplant consultant in Vall d Hebron University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06611046
- Sponsor's protocol ID
- PR(AG)46/2019
- Status last verified
- Sep 2024
- First submitted
- 19 Sep 2024
- Last updated
- 24 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dalmau M, Charco R, Bilbao I, Dopazo C, Caralt M, Molino JA, Gomez-Gavara C. Heparinase I treatment to overcome RNA quantification interference in heparinized liver donor samples: One size fits all? PLoS One. 2025 May 12;20(5):e0322899. doi: 10.1371/journal.pone.0322899. eCollection 2025.
PubMed 40354476
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perfil De MicroRNA Como Biomarcador De Daño Hepático En Diferentes Tipos De Donantes De Hígado (MicroRNA Profile As a Biomarker of Liver Damage in Different Types of Liver Donors).
- ClinicalTrials.gov ID
- NCT06611046
- Acronym / sponsor ID
- PR(AG)46/2019
- Conditions
- MicroRNA Profile, Liver Transplant, Organ Donor
- Keywords
- microRNA, Liver donors, Liver transplant, heparinase
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Mar DalmauUniversity, hospital or other
- Collaborators
- Vall Hebron Insitut Recerca
- Study start
- 2 Oct 2019 (actual)
- Primary completion
- 27 Jul 2021 (actual)
- Study completion
- 1 Sep 2024 (actual)
- First posted
- 24 Sep 2024 (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.
The goal of this observational study is to analyze the expression of liver-derived miRNAs in different types of liver donors to gain in depth knowledge about distinctive physiologic features within donors and find potential biomarkers for graft quality assessment. The main questions it aims to answer are:
Is there a distinctive miRNA profile between donors after brain-stem death and donors after circulatory death?
Is heparinase I treatment necessary to overcome miRNA quantification interference in heparinized liver donor samples ?
Researchers will compare miRNA expression in donors after brain-stem death and donors after circulatory death with I) a subgroup of donors with unusable grafts due to significant steatosis, 2) and with a subgroup of healthy controls undergoing elective cholecystectomy to set the reference miRNA profiles in extreme conditions.
Detailed description
Between October 2019 and May 2021, perfusates, liver biopsies and serum samples were collected prospectively from adult deceased organ donors in Vall d\'Hebron University Hospital, Barcelona, Spain.
Samples from adult human brain death donors (n=10) and donors after circulatory death (n=10) were analyzed for the presence of miR-122, miR-148, miR-155, miR-22, miR-222 and ratio miR122/miR222, target biomarkers of liver injury selected from the literature.
To set the reference miRNA profiles, a subgroup of donors with unusable grafts due to significant steatosis (n=3) were analyzed.
Donors for re-transplantation, pediatric, and split were excluded to avoid biopsy-related injury.
As there were no living donor inclusions in the study period, serum specimens from a subgroup of healthy controls undergoing elective cholecystectomy (n=7) were analyzed.
This study is part of a PhD thesis and data collection was done by the main investigator based in organ donor availability in one tertiary hospital centre in Barcelona, Spain. Based on resource limitation constraints, the sample size was limited to the consecutive samples obtained in a 2-year period.
Written informed consent was obtained from patients and relatives of donors included in the study. Samples and data from patients were provided by the Vall d'Hebron University Hospital Biobank (PT20/00107), integrated in the Spanish National Biobanks Network, and they were processed following standard operating procedures. The study protocol was approved by the medical ethics committee of the Vall d'Hebron University Hospital [PR(AG)46/2019] and conforms to the principles outlined in the Declaration of Helsinki.
Statistical analysis:
To optimize the quality of data, readings with extreme Ct values (Ct less than 11 or Ct greater than 39) were discarded. The mean of the Cts and the standard deviation for each of the miRNAs in the different samples analyzed (technical triplicates) were calculated. To improve the quality of the data analyzed, in triplicates with high standard deviation (Ct SD greater than 0.3), the Ct value furthest from the mean was eliminated, leaving a total of at least two values per miRNA per sample. Likewise, for each miRNA, samples with less than two valid replicates were excluded. To correct for potential RNA input or RT efficiency biases, Ct values were normalized using the average Ct of endogenous references (miR-103a, miR-191, miR-30c, miR-16 and let7a). miRNA relative quantification (RQ) levels were analyzed using the Livak et al. method 2^(-ΔΔCt), calculated as follows ΔCt (miRNA Ct target - averaged endogenous control Ct) and the difference (ΔΔCt) between comparison groups (ΔCt comparison - ΔCt reference sample. Group comparisons were performed using T-test or U-Mann Whitney (non-parametric) for continuous data and Fisher test for qualitative. P-values less than 0.05 were considered significant.
Methodology substudy:
A subgroup of adult human brain death donors (n=4) and donors after circulatory death (n=4) were analyzed for the presence of miR-122 and miR-148. Heparin is known to have an inhibiting effect in RNA qPCR analysis and liver donor samples are prone to have heparin traces, as it\'s used to avoid thrombus formation during organ procurement. Heparinase-I has been used in the literature to overcome the heparin inhibiting effect.
In this substudy, the samples were treated with 0 IU, 6 IU or 12 IU of heparinase-I to evaluate the counteracting effect of heparinase I on miRNA detection levels by RT-qPCR.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 3 Years
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Death brain donors (DBD) | – | Other: organ donorLiver grafts from brain death donors suffer systemic haemodynamic, inflammatory and endocrine changes during donor maintenance due to brain-stem activity cessation. |
| Donors after circulatory death (DCD) | – | Other: organ donorCirculatory death donors do not suffer the physiologic features from brain death, almost mirroring a living donation. However, after withdrawal of life-sustaining measures these grafts suffer injury from severe ischemia. |
| Discarded DBD (dDBD) | – | Other: organ donorLiver grafts from brain death donors that were unusable due to moderate to severe steatosis. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary non-function, early allograft dysfunction and post-transplant vascular and biliary complications |
| Control group | – | Other: organ donorSerum samples from healthy patients who underwent elective cholecystectomy due to symptomatic gallstones were collected before incision. The patients included shared similar characteristics according to the centre living liver donor policy: 18 to 60-year-old, normal liver function and no steatosis in ultrasound. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Fourteen combined perfusates, liver biopsies and serum samples were collected prospectively from brain death donors (DBD, n=14) and donors after circulatory death (DCD, n=14). Three combined perfusates, liver biopsies and serum samples were collected prospectively from brain death donors discarded for transplantation due to significant steatosis (DBDd, n=3). Seven serum samples were collected prospectively from healthy controls undergoing elective cholecystectomy (Control, n=7). Single centre study with samples collected at Vall d'Hebron University Hospital, Spain, between October 2019 and May 2021.
Key inclusion criteria (3 listed)
- Adult deceased liver donors
- Unusable grafts for transplantation due to moderate (30% to 60%) or severe (more than 60%) steatosis in liver biopsies.
- Same inclusion criteria as the living liver donor program in our center: 18 to 60 years old, normal liver function, ultrasound without signs of liver disease and steatosis less than 30%.
Key exclusion criteria (10 listed)
- Pediatric donors (less than18 year-old)
- Donors for re-transplantation cases
- Donors who underwent split or partition liver technique to obtain two small grafts for two recipients (adult and pediatric).
- Discarded DBD grafts:
- Unusable grafts discarded for other reasons.
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 |
|---|---|---|
| organ donorObservational study with sample collection of serum, liver tissue and perfusate fluid from liver donors. No specific interventions were done to the donors as part of the study. The samples were analyzed for specific microNA expression by RT-qPCR. *Control group: only serum samples were collected from this group. | Other | Control group, Death brain donors (DBD), Discarded DBD (dDBD), Donors after circulatory death (DCD) |
Primary outcome
miRNA expression profile in different types of liver donors.
Time frame: Data collection from regional donors in a period of two years based on donor availability and main investigator (data collector) availability. The samples were collected during organ procurement which entails over 4 to 6 hours in each donor.
Compare the miRNA expression profile (miR-122 and miR-148a, miR-222, miR-22 and miR-155) from death brain donors and circulatory death donors in liver biopsies, serum and perfusion solution
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
- Derived from this study: PubMed 40354476Dalmau M, Charco R, Bilbao I, Dopazo C, Caralt M, Molino JA, Gomez-Gavara C. Heparinase I treatment to overcome RNA quantification interference in heparinized liver donor samples: One size fits all? PLoS One. 2025 May 12;20(5):e0322899. doi: 10.1371/journal.pone.0322899. eCollection 2025.
- 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.
Ramon Charco, MD, PhD study director
Chief of HPB surgery and Transplant Department in Vall d Hebron University Hospital
Concepción Gómez-Gavara, MD, PhD study director
HPB surgery and Liver Transplant consultant in Vall d Hebron University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of MicroRNA Profile and Liver Transplant, run by Mar Dalmau at 1 site in Spain.
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 3 inclusion and 10 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: finished, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
miRNA expression profile in different types of liver donors. (time frame: Data collection from regional donors in a period of two years based on donor availability and main investigator (data collector) availability. The samples were collected during organ procurement which entails over 4 to 6 hours in each donor.). 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 NCT06611046, 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 24 Sep 2024.