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

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: Completed
• Conditions: Coronary Artery Bypass; Aortic Valve Disease; Cardiac Surgical Procedures; Mitral Valve Disease
• Intervention / Treatment: Other: Placebo; Drug: 5-Aminolevulinic Acid hydrochloride (5-ALA); Drug: Sodium ferrous citrate (SFC)

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: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Change from baseline HO-1 expression to time of 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		Up to 72 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment related emergent AEs [safety and tolerability]	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	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	Cardiac troponin area under the curve for 72 hours	Serial measurements until 72 hours after release of aortic cross clamping

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: George Clinical Pty Ltd; SBI Pharmaceuticals Co, Ltd.
• Investigators: Principal Investigator: Arash Yavari, DPhil MRCP, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: May 3, 2022
• First Submitted That Met QC Criteria: June 10, 2025
• First Posted (Actual): June 18, 2025

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 19, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: aortic valve replacement; cardiopulmonary bypass; mitral valve surgery; 5-aminolevulinic acid; HO-1; heme oxygenase; delta aminolevulinic acid; sodium ferrous citrate
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Aortic Valve Disease; Physiological Effects of Drugs; Dermatologic Agents; Trace Elements; Micronutrients; Photosensitizing Agents; Aminolevulinic Acid; Ferrous citrate
• Other Study ID 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