N-Acetylcysteine Protection Against Radiation Induced Cellular Damage (CARAPACE)

August 1, 2023 updated by: Claudio Tondo, Centro Cardiologico Monzino

Cardiac Arrhythmia Catheter Ablation Procedures Guided by x-Ray Imaging: N-Acetylcysteine Protection Against Radiation Induced Cellular damagE (CARAPACE Study)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CARAPACE is a prospective, randomized, single-blinded, parallel-arm monocenter study. Eligible patients undergoing CAP at the Arrhythmology Unit of Centro Cardiologico Monzino will be enrolled.

The hypothesis driving our study, based on published literature and our preliminary data, is that administration of antioxidant agents, before cardiac procedures involving IR exposure, might prevent IR harmful effects on human tissues in terms of reduction of systemic oxidative stress status and, in parallel, of oxidative DNA damage.

The antioxidant agent tested in our study is NAC. NAC is a well-tolerated and safe medication and it has antioxidant properties is based on three main mechanisms: 1) direct antioxidant effect, 2) glutathione (GSH) precursor action, and 3) its activity in breaking thiolated proteins.

Another hypothesis to be tested is whether genes involved in DNA damage repair could explain the great variability in patient radiosensitivity to IR exposure and whether these genes could affect NAC protective/healing effects.

Study Type

Interventional

Enrollment (Estimated)

550

Phase

  • 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 Contact

Study Contact Backup

Study Locations

  • Italy
    • MI
      • Milano, MI, Italy, 20138
        • Recruiting
        • Centro Cardiologico Monzino

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

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: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pharmacological treatment
Patients are treated with NAC prior to carrying out CAP.
Drug: Acetyl cysteine
1200 mg of NAC are intravenously administrated 1 hour prior to carrying out CAP.
No Intervention: Standard procedure
Patients are not treated with NAC. No placebo treatment is performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Time Frame: 48 hours
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)).
Time Frame: 48 hours
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 (FT, DAP and ED) between the two groups (NAC versus no NAC).
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.
Time Frame: 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 between the two groups (NAC versus no NAC).
48 hours
Measurement of change in the response to NAC administration related to inherited variants in genes involved in DNA damage repair.
Time Frame: 48 hours
48 hours

Collaborators and Investigators

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

Sponsor

Centro Cardiologico Monzino

Collaborators

Ministry of Health, Italy

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

Helpful Links

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)

September 2, 2020

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

October 17, 2019

First Submitted That Met QC Criteria

November 4, 2019

First Posted (Actual)

November 7, 2019

Study Record Updates

Last Update Posted (Actual)

August 2, 2023

Last Update Submitted That Met QC Criteria

August 1, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCM1006

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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