Impact of Antioxidant Agents on the Number of DNA Double-strand Breaks After Radiation-based Cardiac Examinations

Study Overview
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Brief Summary
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Trial with medicinal products Recent studies revealed that radiation-based procedures in patients may lead to DNA double-strand breaks in human blood lymphocytes. Additionally, ex vivo studies with human blood lymphocytes have shown a protective effect of antioxidant agents which have been described to decrease the number of DNA double-strand breaks. This study represents a prospective, double-blinded, randomized, single center, and placebo-controlled phase II clinical trial which analyzes the capability of antioxidant agents to decrease the number of DNA double-strand breaks in human blood lymphocytes in patients undergoing radiation-based cardiac examinations (30 patients with high-dose radiation exposure, 30 patients with low-dose radiation exposure, and 30 subjects without radiation exposure). A protective effect of antioxidant drugs in patients undergoing radiation-based examinations could therefore change patient management and would provide an important clinical impact.

Official Title
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Randomized, Double-blinded, Placebo-controlled, Single Center, and Prospective Phase II Clinical Trial to Analyze the Effects of Antioxidant Agents on DNA Double-strand Breaks in Patients After Radiation-based Cardiac Examinations

Conditions
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Focus of the Study: DNA Damage Due to Medical Diagnostic X-ray

Intervention / Treatment
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* Radiation: Low-dose radiation exposure
* Radiation: High-dose radiation exposure
* Other: No radiation exposure


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or Female 18-70 years of age European origin Non-smoker 30 patients with high-dose radiation exposure from a cardiac examination 30 patients with low-dose radiation exposure from a cardiac examination 30 subjects without radiation exposure Given written informed consent Ability to participate in the study Exclusion criteria: no known intolerance against one of the applied study drugs or against substances used for formulation of one of the study drugs or against other drugs with similar chemical structures as one of the study drugs Leukemia Lymphoma Radio- or chemotherapy Severe renal failure (GFR<30 ml/min) Positive pregnancy test or lactation Radiation-based examination within the last 3 days Known glucose-6-phosphate-dehydrogenase deficiency Known nephrolithiasis (calciumoxalate calculus) Intake of barbiturates, tetracyclines, corticosteroids within the last 4 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine<br>This arm consists of 30 patients who will receive 1200mg n-acetylcysteine dissolved in 50ml NaCl 0.9% iv before either low-dose (10 patients) or high-dose (10 patients) radiation exposure, or no radiation exposure (10 patients) | Radiation: Low-dose radiation exposure<br>* what: Cardiac CT; dosage: approx. 2-3 mSv; frequency: once<br>Radiation: High-dose radiation exposure<br>* what: cardiac catheterization procedures; dosage: approx. 75 mSv; frequency: once<br>Other: No radiation exposure<br>* Subjects not undergoing any radiation exposure<br>|
| Experimental: Ascorbic acid<br>This arm consists of 30 patients who will receive 3000 mg ascorbic acid dissolved in 50 ml NaCl 0.9% iv before either low-dose (10 patients) or high-dose (10 patients) radiation exposure, or no radiation exposure (10 patients) | Radiation: Low-dose radiation exposure<br>* what: Cardiac CT; dosage: approx. 2-3 mSv; frequency: once<br>Radiation: High-dose radiation exposure<br>* what: cardiac catheterization procedures; dosage: approx. 75 mSv; frequency: once<br>Other: No radiation exposure<br>* Subjects not undergoing any radiation exposure<br>|
| Placebo Comparator: Sodium Chloride (NaCl)<br>This arm consists of 30 patients who will receive 50 ml NaCl 0.9% iv before either low-dose (10 patients) or high-dose (10 patients) radiation exposure, or no radiation exposure (10 patients) | Radiation: Low-dose radiation exposure<br>* what: Cardiac CT; dosage: approx. 2-3 mSv; frequency: once<br>Radiation: High-dose radiation exposure<br>* what: cardiac catheterization procedures; dosage: approx. 75 mSv; frequency: once<br>Other: No radiation exposure<br>* Subjects not undergoing any radiation exposure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of DNA double-strand breaks under influence of antioxidant agents vs. placebo | Potential change (before and after radiation exposure) in the number of DNA double-strand breaks under the influence of n-acetylcystein or ascorbic acid will be measured by qualitative and quantitative immunofluorescence studies (immunofluorescence microscopy and FACS analysis) and will be compared to study patients administered with placebo (using the same quantifiaction tools). | Baseline blood draw before radiation exposure and follow-up blood draw approx. 30 minutes after radiation exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of DNA double-strand breaks between n-acetylcysteine and ascorbic acid | Potential change (before and after radiation exposure) in the number of DNA double-strand breaks from patients administered with n-acetylcysteine compared to the number of DNA double-strand breaks from patients administered with ascorbic acid. The change in the number of DNA double-strand breaks will be measured by qualitative and quantitative immunofluorescence studies (immunofluorescence microscopy and FACS analysis). | Baseline blood draw before radiation exposure and follow-up blood draw approx. 30 minutes after radiation exposure | 
| Change in the number of DNA double-strand breaks between no, low, and high radiation exposure | Potential change (before and after radiation exposure) in the number of DNA double-strand breaks between the different study interventions (low-dose radiation exposure, high-dose radiation exposure, and no radiation exposure). The change in the number of DNA double-strand breaks will be measured by qualitative and quantitative immunofluorescence studies (immunofluorescence microscopy and FACS analysis). | Baseline blood draw before radiation exposure and follow-up blood draw approx. 30 minutes after radiation exposure |