N-Acetylcysteine Protection Against Radiation Induced Cellular Damage

NCT04154982 | Completed Phase 2

• 1 other identifier: CCM1006
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 1

Brief Summary

Catheter ablation procedures (CAPs) are first line treatment for a great variety of cardiac arrhythmias. CAPs require X-Ray imaging; consequently, CAPs cause ionizing radiation (IR) exposure for patients. Exposure to IR, even at low-doses, increases individual risk of developing cancer. IR cause DNA damage directly and, mostly, indirectly by formation of cellular free radicals. Furthermore different response to IR results from inherited variants in genes involved in DNA damage repair. N-acetylcysteine (NAC) is an aminoacid that can directly neutralize free radicals and increase antioxidant systems. Our preliminary data suggest that IR exposure in patients undergoing CAP deranges the oxidative stress status and the pre-procedure intravenous administration of NAC could decrease such abnormality.

Conditions

Cardiac Arrhythmia

Keywords

Electrophysiology; Arrhythmias; Arrhythmia ablation; Ionizing radiation risk; Oxidative stress; DNA damage biomarkers

Outcome Measures

Primary Outcomes (1)

• Measurement of change in systemic oxidative stress (ratio between GSH oxidized form (GSSG) and GSH, 8-iso-prostaglandinF2α (8-iso-PGF2α) and 8-hydroxy-2-deoxyguanosine (8-OHdG)) and genomic DNA oxidative damage (percentage of DNA present in the tails).

  Measurement of change in systemic oxidative stress (GSSG/GSH, 8-iso-PGF2α and 8-OHdG) and genomic DNA oxidative damage (% DNA present in the tails of the comet assay) between the two groups (NAC versus no NAC) at the different time-points (T0 = before CAP, T1 = 3h after CAP, T2 = 24h after CAP, T3 = 48h after CAP).

  48 hours

Secondary Outcomes (3)

• Measurement of change in systemic oxidative stress (GSSG/GSH, 8-iso-PGF2α and 8-OHdG) and genomic DNA oxidative damage (% DNA present in the tails) related to IR dose (fluoroscopy time (FT), Dose Area Product (DAP) and effective dose (ED)).

  48 hours

• Measurement of change in genomic DNA oxidative damage (% DNA present in the tails) related to IR dose (FT, DAP and ED) and inherited variants in genes involved in DNA damage repair.

  48 hours

• Measurement of change in the response to NAC administration related to inherited variants in genes involved in DNA damage repair.

  48 hours

Study Arms (2)

Pharmacological treatment

EXPERIMENTAL

Patients are treated with NAC prior to carrying out CAP.

Drug: Acetyl cysteine

Standard procedure

NO INTERVENTION

Patients are not treated with NAC. No placebo treatment is performed.

Interventions

Acetyl cysteine DRUG

1200 mg of NAC are intravenously administrated 1 hour prior to carrying out CAP.

Pharmacological treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's age \>18 years.
• Negative hCG pregnancy test (if appropriate).
• Indication to perform CAP guided by fluoroscopy (IR imaging).
• Ability and willingness to give informed consent and to comply with protocol.

You may not qualify if:

• Any contraindication to CAP (such as, pregnancy and breastfeeding).
• Hypersensitivity to the active substance or to any of the excipients.
• Enrollment in another study that may interfere with CARAPACE study.
• Administration of an experimental drug within 30 days or 5 half-lives of the investigational drug.
• Chronic kidney disease (serum creatinine \>1.5 mg/dl).
• Acute/Chronic inflammatory disease.
• Antioxidant drugs intake over the previous 2 weeks.
• History of radiotherapy or chemotherapy in the last year.
• Any documented condition that, in PI's motivated judgement, makes the patient a poor candidate for the study.
• Computed tomography and/or coronary angiography within 5 days prior to baseline analysis.

Sponsors & Collaborators

• Centro Cardiologico Monzino: lead
• Ministry of Health, Italy: collaborator

Study Sites (1)

Centro Cardiologico Monzino

Milan, MI, 20138, Italy

Location

Related Publications (15)

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• Squellerio I, Caruso D, Porro B, Veglia F, Tremoli E, Cavalca V. Direct glutathione quantification in human blood by LC-MS/MS: comparison with HPLC with electrochemical detection. J Pharm Biomed Anal. 2012 Dec;71:111-8. doi: 10.1016/j.jpba.2012.08.013. Epub 2012 Aug 23.

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• Turnu L, Di Minno A, Porro B, Squellerio I, Bonomi A, Manega CM, Werba JP, Parolari A, Tremoli E, Cavalca V. Assessing Free-Radical-Mediated DNA Damage during Cardiac Surgery: 8-Oxo-7,8-dihydro-2'-deoxyguanosine as a Putative Biomarker. Oxid Med Cell Longev. 2017;2017:9715898. doi: 10.1155/2017/9715898. Epub 2017 Jun 4.

  PMID: 28660009 BACKGROUND

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• Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007 Sep;81(3):559-75. doi: 10.1086/519795. Epub 2007 Jul 25.

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• Amadio P, Colombo GI, Tarantino E, Gianellini S, Ieraci A, Brioschi M, Banfi C, Werba JP, Parolari A, Lee FS, Tremoli E, Barbieri SS. BDNFVal66met polymorphism: a potential bridge between depression and thrombosis. Eur Heart J. 2017 May 7;38(18):1426-1435. doi: 10.1093/eurheartj/ehv655.

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• Casella M, Dello Russo A, Russo E, Catto V, Pizzamiglio F, Zucchetti M, Majocchi B, Riva S, Vettor G, Dessanai MA, Fassini G, Moltrasio M, Tundo F, Vignati C, Conti S, Bonomi A, Carbucicchio C, Di Biase L, Natale A, Tondo C. X-Ray Exposure in Cardiac Electrophysiology: A Retrospective Analysis in 8150 Patients Over 7 Years of Activity in a Modern, Large-Volume Laboratory. J Am Heart Assoc. 2018 May 22;7(11):e008233. doi: 10.1161/JAHA.117.008233.

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• Catto V, Stronati G, Porro B, Fiorelli S, Ricci V, Vavassori C, Russo E, Guerra F, Gasperetti A, Ribatti V, Sicuso R, Dello Russo A, Veglia F, Tondo C, Cavalca V, Colombo GI, Tremoli E, Casella M. Cardiac arrhythmia catheter ablation procedures guided by x-ray imaging: N-acetylcysteine protection against radiation-induced cellular damage (CARAPACE study): study design. J Interv Card Electrophysiol. 2021 Sep;61(3):577-582. doi: 10.1007/s10840-020-00853-4. Epub 2020 Aug 24.

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Related Links

• Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging
• National Research Council. 2006. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: The National Academies Press.

MeSH Terms

Conditions

Arrhythmias, Cardiac

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Researchers, involved in the assessment of NAC efficacy, are blinded to randomization process; thus, they do not know whether the patients are in the NAC or in the control groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy of Heart Rhythm Center

Study Record Dates

• First Submitted: October 17, 2019
• First Posted: November 7, 2019
• Study Start: September 2, 2020
• Primary Completion: December 2, 2024
• Study Completion: December 2, 2024
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)