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

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

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.

Study Overview

• Status: Completed
• Conditions: Focus of the Study: DNA Damage Due to Medical Diagnostic X-ray
• Intervention / Treatment: Radiation: Low-dose radiation exposure; Radiation: High-dose radiation exposure; Other: No radiation exposure

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zurich, ZH, Switzerland, 8091
      • University Hospital Zurich, Division of Nuclear Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: N-acetylcysteine; 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; what: Cardiac CT; dosage: approx. 2-3 mSv; frequency: once; Radiation: High-dose radiation exposure; what: cardiac catheterization procedures; dosage: approx. 75 mSv; frequency: once; Other: No radiation exposure; Subjects not undergoing any radiation exposure
EXPERIMENTAL: Ascorbic acid; 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; what: Cardiac CT; dosage: approx. 2-3 mSv; frequency: once; Radiation: High-dose radiation exposure; what: cardiac catheterization procedures; dosage: approx. 75 mSv; frequency: once; Other: No radiation exposure; Subjects not undergoing any radiation exposure
PLACEBO_COMPARATOR: Sodium Chloride (NaCl); 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; what: Cardiac CT; dosage: approx. 2-3 mSv; frequency: once; Radiation: High-dose radiation exposure; what: cardiac catheterization procedures; dosage: approx. 75 mSv; frequency: once; Other: No radiation exposure; Subjects not undergoing any radiation exposure

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Zurich
• Investigators: Principal Investigator: Philipp Kaufmann, MD, University Hospital Zurich, Division of Nuclear Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: April 12, 2012
• First Submitted That Met QC Criteria: April 13, 2012
• First Posted (ESTIMATE): April 16, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 6, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Other Study ID Numbers: KEK-ZH-NR: 2010-0352