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

Primary Purpose

Cardiac Arrhythmia

Status

Recruiting

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

Acetyl cysteine

About this trial

This is an interventional treatment trial for Cardiac Arrhythmia focused on measuring Electrophysiology, Arrhythmias, Arrhythmia ablation, Ionizing radiation risk, Oxidative stress, DNA damage biomarkers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Centro Cardiologico MonzinoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Pharmacological treatment

Standard procedure

Arm Description

Patients are treated with NAC prior to carrying out CAP.

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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)).

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.

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.

Full Information

NCT ID

NCT04154982

First Posted

October 17, 2019

Last Updated

August 1, 2023

Sponsor

Centro Cardiologico Monzino

Collaborators

Ministry of Health, Italy

1. Study Identification

Unique Protocol Identification Number

NCT04154982

Brief Title

N-Acetylcysteine Protection Against Radiation Induced Cellular Damage

Acronym

CARAPACE

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 2, 2020 (Actual)

Primary Completion Date

December 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centro Cardiologico Monzino

Collaborators

Ministry of Health, Italy

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiac Arrhythmia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

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.

Allocation

Randomized

Enrollment

550 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pharmacological treatment

Arm Type

Experimental

Arm Description

Patients are treated with NAC prior to carrying out CAP.

Arm Title

Standard procedure

Arm Type

No Intervention

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Acetyl cysteine

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

Time Frame

48 hours

Secondary Outcome Measure Information:

Title

Description

Time Frame

48 hours

Title

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.

Description

Time Frame

48 hours

Title

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

Time Frame

48 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Claudio Tondo

Phone

+39025800

Ext

2480

claudio.tondo@ccfm.it

First Name & Middle Initial & Last Name or Official Title & Degree

Valentina Catto

Phone

+39025800

Ext

2856

valentina.catto@ccfm.it

Facility Information:

Facility Name

Centro Cardiologico Monzino

City

Milano

State/Province

ZIP/Postal Code

20138

Country

Italy

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

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Links:

URL

http://doi.org/10.1016/j.jacc.2018.02.017

Description

Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging

URL

http://doi.org/10.17226/11340

Description

National Research Council. 2006. Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: The National Academies Press.

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N-Acetylcysteine Protection Against Radiation Induced Cellular Damage

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