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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04154982
Recruitment Status : Recruiting
First Posted : November 7, 2019
Last Update Posted : August 2, 2023
Sponsor:
Collaborator:
Ministry of Health, Italy
Information provided by (Responsible Party):
Claudio Tondo, Centro Cardiologico Monzino

Study Description
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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.

Condition or disease Intervention/treatment Phase
Cardiac Arrhythmia Drug: Acetyl cysteine Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 550 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Cardiac Arrhythmia Catheter Ablation Procedures Guided by x-Ray Imaging: N-Acetylcysteine Protection Against Radiation Induced Cellular damagE (CARAPACE Study)
Actual Study Start Date : September 2, 2020
Estimated Primary Completion Date : December 1, 2024
Estimated Study Completion Date : December 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Arrhythmia

Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  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). [ 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).


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. Measurement of change in the response to NAC administration related to inherited variants in genes involved in DNA damage repair. [ Time Frame: 48 hours ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04154982


Contacts
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Contact: Claudio Tondo +39025800 ext 2480 claudio.tondo@ccfm.it
Contact: Valentina Catto +39025800 ext 2856 valentina.catto@ccfm.it

Locations
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Italy
Centro Cardiologico Monzino Recruiting
Milano, MI, Italy, 20138
Sponsors and Collaborators
Centro Cardiologico Monzino
Ministry of Health, Italy
More Information
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Additional Information:

Publications:

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Responsible Party: Claudio Tondo, Deputy of Heart Rhythm Center, Centro Cardiologico Monzino
ClinicalTrials.gov Identifier: NCT04154982    
Other Study ID Numbers: CCM1006
First Posted: November 7, 2019    Key Record Dates
Last Update Posted: August 2, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Claudio Tondo, Centro Cardiologico Monzino:
Electrophysiology
Arrhythmias
Arrhythmia ablation
 Ionizing radiation risk
Oxidative stress
DNA damage biomarkers
Additional relevant MeSH terms:
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Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
 Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes