Clinical trial NCT04154982: N-Acetylcysteine Protection Against Radiation Induced Cellular Damage
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cardiac Arrhythmia
Keywords: Electrophysiology
Arrhythmias
Arrhythmia ablation
Ionizing radiation risk
Oxidative stress
DNA damage biomarkers
Lead sponsor: Centro Cardiologico Monzino
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Italy
First posted: 2019-11-07
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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).
timeFrame: 48 hours
Secondary outcomes:
measure: 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)).
timeFrame: 48 hours
measure: 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.
timeFrame: 48 hours
measure: Measurement of change in the response to NAC administration related to inherited variants in genes involved in DNA damage repair.
timeFrame: 48 hours
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
state: MI
Study officials:
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