Treatment With 5-AminoLEvuliNic Acid Before Cardiac Surgery (TALEN)

June 19, 2025 updated by: University of Oxford

Pre-operative 5-Aminolevulinic Acid to Activate Haem Oxygenase to Improve Outcomes in Cardiac Surgery: A Dose Finding Study

TALEN is a prospective randomised double-blind placebo-controlled phase 2 study of 5-Aminolevulinic Acid with Sodium Ferrous Citrate (5-ALA-SFC) in adult patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). TALEN aims to identify the optimal biological dose (OBD) of 5-ALA-SFC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

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

TALEN is a prospective, randomised, double blind, placebo-controlled phase 2 study of 5-ALA-SFC administration in adults undergoing non-emergent cardiac surgery on CPB examining the potential of 5-ALA-SFC to induce haem oxygenase-1 (HO-1) as a novel cardio- and cyto-protective strategy for clinical benefit. 5-ALA is an amino acid found in several foods and a natural endogenous precursor in the synthesis of haem. Oral administration of 5-ALA-SFC has been shown to be safe and to induce a pharmacodynamic effect on the key effector, HO-1. TALEN is designed as a dose-finding trial with sequential dose cohorts, evaluating the safety, tolerability and PD response to 5-ALA-SFC to determine the optimum biological dose for further evaluation.

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 (Actual)

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.
48

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

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

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • John Radcliffe Hospital

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:

  • Scheduled for non-emergent cardiac surgery under CPB (including coronary artery bypass grafting, valve replacement, valve repair or a combination thereof)
  • Signed informed consent
  • Age ≥18 years
  • Able and willing to comply with all study requirements

Exclusion Criteria:

  • Female participants who are of childbearing potential who are either unable or unwilling to use highly effective contraception, or who are pregnant or breast feeding
  • History of hypersensitivity to 5-ALA, SFC and/or porphyrins
  • Acute or chronic types of porphyria
  • Known genetic haemochromatosis or clinically significant iron overload
  • History of clinically significant photosensitization
  • Current long-term (> 3 months) use of amiodarone
  • Concomitant use of hypericin extract (including St John's Wort) or concomitant therapeutic dose oral iron replacement
  • Use of other investigational medical product(s) < 28 days prior to study or 5 half-lives, whichever is longer
  • Cardiogenic shock/Low cardiac output syndrome requiring catecholamine infusion and/or mechanical circulatory support prior to induction of anaesthesia for cardiac surgery
  • Recent acute myocardial infarction
  • Cardiac surgery without cardiopulmonary bypass or induced fibrillating heart surgery
  • Inadequate renal or liver function
  • Any other condition which, in the opinion of the Investigator, makes the patient unsuitable for or may compromise their participation in the study

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: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

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.
Placebo Comparator: Placebo
2 patients in each cohort above will be allocated to placebo (n=8 patients in total across the study)
Other: Placebo
Supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing 125mg lactose. The capsule shells are of non-animal origin, and are comprised of HPMC, titanium dioxide, and a copper complex of chlorophyllins.
Experimental: Cohort 1
75 mg 5-ALA with 118 mg SFC bd (lowest/starting dose) for three days before surgery (n=8 patients)
Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)
5-ALA: supplied for oral administration as a dark green, opaque, size 0, hypromellose (HPMC) capsule containing drug alone at a dosage strength of 75mg (58.7mg as 5-ALA). There are no excipients.
Drug: Sodium ferrous citrate (SFC)
SFC: supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing drug alone at a dosage strength 118mg (12.5mg as Fe). There are no excipients.
Experimental: Cohort 2
150 mg 5-ALA with 236 mg SFC or bd for three days before surgery (n=8 patients)
Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)
5-ALA: supplied for oral administration as a dark green, opaque, size 0, hypromellose (HPMC) capsule containing drug alone at a dosage strength of 75mg (58.7mg as 5-ALA). There are no excipients.
Drug: Sodium ferrous citrate (SFC)
SFC: supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing drug alone at a dosage strength 118mg (12.5mg as Fe). There are no excipients.
Experimental: Cohort 3
225 mg 5-ALA with 354 mg SFC bd for three days before surgery (n=8 patients)
Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)
5-ALA: supplied for oral administration as a dark green, opaque, size 0, hypromellose (HPMC) capsule containing drug alone at a dosage strength of 75mg (58.7mg as 5-ALA). There are no excipients.
Drug: Sodium ferrous citrate (SFC)
SFC: supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing drug alone at a dosage strength 118mg (12.5mg as Fe). There are no excipients.
Experimental: Cohort 4
300 mg 5-ALA with 472 mg SFC bd (maximum dose) for three days before surgery (n=8 patients)
Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA)
5-ALA: supplied for oral administration as a dark green, opaque, size 0, hypromellose (HPMC) capsule containing drug alone at a dosage strength of 75mg (58.7mg as 5-ALA). There are no excipients.
Drug: Sodium ferrous citrate (SFC)
SFC: supplied for oral administration as a dark green, opaque, size 0, HPMC capsule containing drug alone at a dosage strength 118mg (12.5mg as Fe). There are no excipients.

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
Change from baseline HO-1 expression to time of cardiac surgery
Time Frame: Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)

Normalised HO-1 expression in peripheral blood

•Safety: Occurrence of adverse events / laboratory safety events defined as dose-limiting toxicity (DLTs)
Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
Number of Participants With Dose Limiting Toxicity
Time Frame: Up to 72 hours post-surgery
Up to 72 hours post-surgery

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
Incidence of treatment related emergent AEs [safety and tolerability]
Time Frame: From time of administration of placebo or investigational medicinal product (IMP) (i.e. treatment-emergent AEs, TEAEs) to 72 hours post-operatively
Treatment-related AEs assessed using CTCAE v5.0
From time of administration of placebo or investigational medicinal product (IMP) (i.e. treatment-emergent AEs, TEAEs) to 72 hours post-operatively
Change from baseline HO activity to time of cardiac surgery
Time Frame: Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
HO enzyme activity
Baseline at screening compared to post dose (measured within 12 hours of final dose, before cardiac surgery)
Preliminary evaluation of the kinetics of peri-operative myocardial injury
Time Frame: Serial measurements until 72 hours after release of aortic cross clamping
Cardiac troponin area under the curve for 72 hours
Serial measurements until 72 hours after release of aortic cross clamping

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.
University of Oxford

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
George Clinical Pty Ltd
SBI Pharmaceuticals Co, Ltd.

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: Arash Yavari, DPhil MRCP, University of Oxford

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.
February 1, 2021

Primary Completion (Actual)

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 30, 2022

Study Completion (Actual)

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.
June 30, 2022

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).
May 3, 2022

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 10, 2025

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 18, 2025

Study Record Updates

Last Update Posted (Estimated)

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 25, 2025

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 19, 2025

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.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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.
  • 280513

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

No

Studies a U.S. FDA-regulated device product

No

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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