Secretin in Ex-situ Liver Perfusion

June 11, 2026 updated by: Prof. Robert J. Porte, Erasmus Medical Center

Secretin Therapy During Ex-Situ Normothermic Liver Machine Perfusion: A Critical Factor for Restoration of Bile Duct Physiology and the Protective "Bicarbonate Umbrella"

The main objective is to assess whether the use of human synthetic secretin in a clinical (COR-)NMP procedure can restore physiological HCO3- content of the bile during ex-situ NMP.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Liver transplantation is the only curative treatment option for patients with end-stage liver disease, but it is limited by a large gap between the number of patients in need and donor organs available. Strikingly, in 2021, 38% of available donor livers were disposed being assessed as non-transplantable in The Netherlands, while approximately 20% of patients on the liver transplant waitlist died or became too sick to be transplanted. Similar or even higher discard rates are observed in other countries, such as the US. Acceptance of extended criteria donor (ECD) livers, referring to suboptimal grafts from older, obese, or otherwise comorbid donors and organs from donation after circulatory death (DCD), is proposed to meet this growing demand. However, transplantation of these livers is associated with a higher rate of post-operative complications, increased hospital costs and reduced graft survival, compared to standard grafts.

Machine perfusion (MP) is a dynamic, isolated platform to preserve liver grafts out-of-the-body by circulation of an oxygenated perfusate. While dual hypothermic oxygenated perfusion (DHOPE) reconditions the graft in a hypometabolic state, normothermic MP (NMP) allows full assessment of metabolic function at physiological temperatures. The sequential protocol of both perfusion techniques, with controlled oxygenated rewarming for 60 minutes (COR), named DHOPE-COR-NMP is currently used in clinical practice for viability assessment of high-risk ECD-livers prior to transplantation. The decision moment whether a liver is suitable for transplantation is after 150 minutes of NMP. Unfortunately, one third of these tested livers are currently discarded, mainly because of not meeting the predefined criteria for cholangiocyte viability (own, unpublished data). The platform of MP allows graft reconditioning in an isolated circuit, with no systemic effects of administered therapeutics in the recipient as the liver is thoroughly flushed out before implantation in the recipient, thereby limiting side-effects.

Secretin is a hormone with a short half-life that is produced in the duodenum, with systemic effects. In the liver, secretin stimulates cholangiocytes through the secretin receptor. This leads to an increase in intracellular cyclic AMP (cAMP), subsequently activating Protein kinase A (PKA), eventually leading to a downstream excretion of chloride through the CFTR channels. Chloride is a leading force in bicarbonate excretion, as this excreted chloride is resorbed through Anion-Exchanger-2 (AE2) and exchanged for bicarbonate. In a physiological setting, cholangiocytes are protected from bile-acid injury by this "bicarbonate umbrella". With the excretion of bicarbonate, water is also excreted through Aquaporin-1 (AQP-1), and thus increasing total bile production. The increase in bile production is one of the main reasons for secretin to be administered during Magnetic Resonance Cholangio-Pancreatography (MRCP) imaging of the biliary tree in its current application as diagnostic tool.

The perfusate that is used for NMP, is based on an oxygen carrier (currently red blood cells), colloids and certain supplements to reach a near-physiological environment in oncotic pressure and nutrients. In physiological conditions, bile contains high amounts of bicarbonate, resulting in an alkalotic fluid. This earlier mentioned "bicarbonate umbrella" protects the cholangiocytes from bile acid-induced injury. During NMP, bile pH and bile bicarbonate levels are lower compared to a physiological setting (own, unpublished data). The investigators hypothesize that cholangiocytes during NMP are not able to demonstrate their full potential, as they are not stimulated by secretin like in-vivo physiology. As explained earlier, the increase in bile production is a result of increasing bicarbonate excretion, and thereby biliary pH, creating a more physiological environment for the liver and bile ducts. Possible further injury of the bile duct from bile acid toxicity could be prevented by adding secretin to the perfusate during COR-NMP. This however, can only be researched after this initial validation of the safety and efficacy of secretin as a missing component to reach physiological conditions during ex-situ liver NMP.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 GD
        • Erasmus Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients (>18 years old)
  • Donor livers that required resuscitation and viability assessment through the previously published sequential hypo- and normothermic liver machine perfusion (DHOPE-COR-NMP) protocol based on a blood-based perfusate.

Exclusion Criteria:

  • Multiorgan transplantation
  • Split liver transplant
  • Living donor liver transplantation
  • Organ donation after Euthanasia
  • Previous donor organ perfusion (e.g. Normothermic Regional Perfusion)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Historical control group
Historical cases of sequential hypo- to normothermic machine perfusion, linked with controlled oxygenated rewarming for 60 minutes (DHOPE-COR-NMP) livers that did not receive synthetic human secretin during the perfusion.
Experimental: Secretin administration during liver machine perfusion (COR-NMP)
These livers will be treated during ex-situ machine perfusion with a blood-based perfusate with doses of human synthetic secretin.
Drug: Secretin administration during ex-situ liver machine perfusion

In at least 20 cases of sequential hypo- to normothermic machine perfusion, linked with controlled oxygenated rewarming (COR) for 60 minutes (DHOPE-COR-NMP) livers, the investigators will add 16mcg of synthetic human secretin to the perfusate at the start of COR phase of the protocol and a second dose of 16mcg during the NMP phase after the decision moment whether to transplant or not. This number was chosen based on an average acceptance rate of 70%, and therefore would generate 14 transplanted livers while 6 livers are expected not to be transplanted (not passing the standard viability criteria).

As the acceptance rate is subject to fluctuations over time (due to variations in the quality of donor offers), the investigators want to include at least 14 transplanted livers and 6 livers that are not transplanted (not passing the standard viability criteria), in order to have the best representative situation. When both numbers are reached, inclusions will stop.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cholangiocellular viability assessment - Biliary Bicarbonate
Time Frame: Periprocedural
A comparison will be made between livers that pass cholangiocyte viability assessment and livers that do not pass cholangiocyte viability assessment in the secretin cohort of this study. Analysis will be performed on bile composition, with the main outcome being the response in biliary bicarbonate increase 30 minutes after the second dose of administration (directly after viability assessment with the go-no go for transplantation).
Periprocedural

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cholangiocellular viability assessment - Bile production
Time Frame: Periprocedural
A comparison will be made between livers that pass cholangiocyte viability assessment and livers that do not pass cholangiocyte viability assessment in the secretin cohort of this study. Analysis will be performed on bile production with the volume (mL) increase 30 minutes after the second dose of administration (directly after viability assessment with the go-no go for transplantation).
Periprocedural

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Comparison with historical cohort - Biliary complications
Time Frame: Until 6 months post-transplant
The cohort of livers that are transplanted and were subjected to Secretin at the beginning of controlled oxygenated rewarming (COR) will be compared to similar cases in our historical cohort of transplanted livers after sequential hypo- to normothermic machine perfusion linked with COR (DHOPE-COR-NMP). For descriptive purposes, complication rate, especially anastomotic strictures, ischemic cholangiopathy, bile leaks will be registered, but based on the small numbers and short follow-up in this pilot study will not be analysed.
Until 6 months post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Erasmus Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Robert J Porte, MD, PhD, Erasmus Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 26, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 16, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MEC-2024-0678

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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