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

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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

Tracking Information
First Submitted Date  ICMJE October 17, 2019
First Posted Date  ICMJE November 7, 2019
Last Update Posted Date August 2, 2023
Actual Study Start Date  ICMJE September 2, 2020
Estimated Primary Completion Date December 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2019)		 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
  • 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).
  • 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).
  • Measurement of change in the response to NAC administration related to inherited variants in genes involved in DNA damage repair. [ Time Frame: 48 hours ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE N-Acetylcysteine Protection Against Radiation Induced Cellular Damage
Official Title  ICMJE Cardiac Arrhythmia Catheter Ablation Procedures Guided by x-Ray Imaging: N-Acetylcysteine Protection Against Radiation Induced Cellular damagE (CARAPACE Study)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Cardiac Arrhythmia
Intervention  ICMJE Drug: Acetyl cysteine
1200 mg of NAC are intravenously administrated 1 hour prior to carrying out CAP.
Study Arms  ICMJE
  • Experimental: Pharmacological treatment
    Patients are treated with NAC prior to carrying out CAP.
    Intervention: Drug: Acetyl cysteine
  • No Intervention: Standard procedure
    Patients are not treated with NAC. No placebo treatment is performed.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 4, 2019)		 550
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2024
Estimated Primary Completion Date December 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Claudio Tondo +39025800 ext 2480 claudio.tondo@ccfm.it
Contact: Valentina Catto +39025800 ext 2856 valentina.catto@ccfm.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04154982
Other Study ID Numbers  ICMJE CCM1006
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Claudio Tondo, Centro Cardiologico Monzino
Original Responsible Party Michela Casella, Centro Cardiologico Monzino, Deputy of Heart Rhythm Center
Current Study Sponsor  ICMJE Centro Cardiologico Monzino
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Ministry of Health, Italy
Investigators  ICMJE Not Provided
PRS Account Centro Cardiologico Monzino
Verification Date August 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP