A study comparing the drug 'bezafibrate' against a placebo in the treatment of Barth Syndrome

Treatment of Barth Syndrome by CARDIOlipin MANipulation (CARDIOMAN): A randomised placebo controlled pilot trial conducted by the nationally commissioned Barth Syndrome Service - CARDIOMAN

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-001382-10-GB

Enrollment

Registered

2015-08-24

Start date

2019-01-21

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Barth Syndrome is a rare, life threatening, genetic disease which affects young males. It is caused by abnormal fats (lipids) in the powerhouses of cells (mitochondria) and those who suffer with it often develop heart failure, heart rhythm abnormalities, bacterial infections, poor growth or feeding, weak muscles, developmental delay, severe exercise intolerance, lethargy and fatigue. MedDRA version: 20.0 Level: SOC Classification code 10010331

Interventions

Trade Name: Bezafibrate Product Name: Bezafibrate Pharmaceutical Form: Coated tablet INN or Proposed INN: Bezafibrate (INN 3968) CAS Num

Eligibility

Sex/Gender

Male

Inclusion criteria

Inclusion criteria: • Male aged =6 years old • Clinical diagnosis of Barth Syndrome with characteristic abnormality of the L4-cardiolipin/monolysocardiolipin ratio plus identified mutation in the tafazzin gene • Under the care of the NHS Barth Syndrome Service • Stable cardiac condition • Able to swallow bezafibrate tablets (similar size to Ibuprofen tablets) Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: 1. Known hypersensitivity to bezafibrate, to any component of the product or to other fibrates 2. Known photoallergic or phototoxic reactions to fibrates. 3. Hepatic dysfunction and/or liver function tests greater than 2x normal 4. Unstable cardiac status: a shortening fraction of <25 (or a significant drop in shortening fraction in the previous year) 5. Documented atrial or ventricular arrhythmia (atrial/ventricular tachycardia or atrial/ventricular fibrillation) that has not been stabilised with treatment. 6. Renal impairment (creatinine clearance < 90 mL/min) 7. Pre-existing known gallbladder disease. 8. Recent unspecified significant deterioration in general health 9. Prisoners and adults lacking capacity to provide informed consent

Design outcomes

Primary

Measure	Time frame
Main Objective: What is the effect on clinical and biochemical outcomes and Quality of Life of bezafibrate treatment in comparison to placebo in Barth Syndrome patients?;Primary end point(s): The primary outcome measure is peak oxygen consumption on bicycle ergometry. This will be assessed at baseline and in the final week of each treatment phase.;Timepoint(s) of evaluation of this end point: Peak oxygen consumption will be measured at baseline (before treatment starts), in the last week of the first 4 month treatment phase and then again in the last week of the second 4 month treatment phase.; Secondary Objective: 1. Is there a relationship between improvements in clinical outcomes (such as the ability to tolerate exercise) and laboratory measures of cardiolipin ratio/profile and mitochondrial morphology (shape and structure of the cells) when participants are exposed to bezafibrate. 2. What are the most feasible methods and standardised ways of measuring outcomes that may allow better conduct of future trials (e.g. larger multinational trials) and evaluations in Barth syndrome? 3. Is it possible to create a research infrastructure which optimises recruitment, retention and communication with families and people with Barth syndrome nationwide? 5. What are the participant and family perceptions of research and are there any important potential barriers to participation?	—

Measure

Time frame

Main Objective: What is the effect on clinical and biochemical outcomes and Quality of Life of bezafibrate treatment in comparison to placebo in Barth Syndrome patients?;Primary end point(s): The primary outcome measure is peak oxygen consumption on bicycle ergometry. This will be assessed at baseline and in the final week of each treatment phase.;Timepoint(s) of evaluation of this end point: Peak oxygen consumption will be measured at baseline (before treatment starts), in the last week of the first 4 month treatment phase and then again in the last week of the second 4 month treatment phase.; Secondary Objective: 1. Is there a relationship between improvements in clinical outcomes (such as the ability to tolerate exercise) and laboratory measures of cardiolipin ratio/profile and mitochondrial morphology (shape and structure of the cells) when participants are exposed to bezafibrate. 2. What are the most feasible methods and standardised ways of measuring outcomes that may allow better conduct of future trials (e.g. larger multinational trials) and evaluations in Barth syndrome? 3. Is it possible to create a research infrastructure which optimises recruitment, retention and communication with families and people with Barth syndrome nationwide? 5. What are the participant and family perceptions of research and are there any important potential barriers to participation?

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Secondary

Measure	Time frame
Secondary end point(s): 1. MLCL/L4-CL ratio/cardiolipin profile 2. PCr/ATP ratio in cardiac muscle on 31P Magnetic Resonance Spectroscopy 3. Skeletal muscle oxidative function/ATP production on 31P Magnetic Resonance Spectroscopy 4. Quality of life (QOL) assessed using age-appropriate PedsQL or SF36 questionnaires 5. Absolute neutrophil count 6. Amino acid expression (serum arginine and cysteine levels) 7. Cardiac function (LVEF and shortening fraction) 8. Mitochondrial size 9. Numbers of mitochondria (per lymphocyte) 10. Total area of mitochondria per lymphocyte 11. Area of mitochondria as proportion of cytoplasm 12. Mitochondria function and cristae organisation in lymphocytes 13. Arrhythmia profile from 12 lead ECG at rest and during exercise (for potential rhythm abnormalities) ;Timepoint(s) of evaluation of this end point: Secondary outcomes will be measured at baseline (before treatment starts), in the last week of the first 4 month treatment phase and then again in the last week of the second 4 month treatment phase.	—

Measure

Time frame

Secondary end point(s): 1. MLCL/L4-CL ratio/cardiolipin profile 2. PCr/ATP ratio in cardiac muscle on 31P Magnetic Resonance Spectroscopy 3. Skeletal muscle oxidative function/ATP production on 31P Magnetic Resonance Spectroscopy 4. Quality of life (QOL) assessed using age-appropriate PedsQL or SF36 questionnaires 5. Absolute neutrophil count 6. Amino acid expression (serum arginine and cysteine levels) 7. Cardiac function (LVEF and shortening fraction) 8. Mitochondrial size 9. Numbers of mitochondria (per lymphocyte) 10. Total area of mitochondria per lymphocyte 11. Area of mitochondria as proportion of cytoplasm 12. Mitochondria function and cristae organisation in lymphocytes 13. Arrhythmia profile from 12 lead ECG at rest and during exercise (for potential rhythm abnormalities) ;Timepoint(s) of evaluation of this end point: Secondary outcomes will be measured at baseline (before treatment starts), in the last week of the first 4 month treatment phase and then again in the last week of the second 4 month treatment phase.

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Countries

United Kingdom

Contacts

Public ContactLucy Dabner

University of Bristol

cardioman-trial@bristol.ac.uk01173422374

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026