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

Centro Cardiologico Monzino

Status and phase

Enrolling

Phase 2

Conditions

Cardiac Arrhythmia

Treatments

Drug: Acetyl cysteine

Study type

Interventional

Funder types

Other

Identifiers

NCT04154982

CCM1006

Details and patient eligibility

About

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.

Full 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.

Enrollment

550 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No 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.