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

Purpose

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.

Condition	Intervention	Phase
Focus of the Study: DNA Damage Due to Medical Diagnostic X-ray	Radiation: Low-dose radiation exposure Radiation: High-dose radiation exposure Other: No radiation exposure	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Antioxidants Vitamin C

Drug Information available for: Ascorbic acid Sodium ascorbate Acetylcysteine

U.S. FDA Resources

Further study details as provided by University of Zurich:

Primary Outcome Measures:

Change in the number of DNA double-strand breaks under influence of antioxidant agents vs. placebo [ Time Frame: Baseline blood draw before radiation exposure and follow-up blood draw approx. 30 minutes after radiation exposure ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Change in the number of DNA double-strand breaks between n-acetylcysteine and ascorbic acid [ Time Frame: Baseline blood draw before radiation exposure and follow-up blood draw approx. 30 minutes after radiation exposure ] [ Designated as safety issue: No ]
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).
Change in the number of DNA double-strand breaks between no, low, and high radiation exposure [ Time Frame: Baseline blood draw before radiation exposure and follow-up blood draw approx. 30 minutes after radiation exposure ] [ Designated as safety issue: No ]
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).

Enrollment:	102
Study Start Date:	April 2012
Study Completion Date:	November 2012
Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01578395

Locations

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

Sponsors and Collaborators

University of Zurich

Investigators

Principal Investigator:

Philipp Kaufmann, MD

University Hospital Zurich, Division of Nuclear Medicine

More Information

No publications provided

Responsible Party:	University of Zurich
ClinicalTrials.gov Identifier:	NCT01578395 History of Changes
Other Study ID Numbers:	KEK-ZH-NR: 2010-0352
Study First Received:	April 12, 2012
Last Updated:	December 5, 2012
Health Authority:	Switzerland: Swissmedic

Additional relevant MeSH terms:

Acetylcysteine
Antioxidants
Ascorbic Acid
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants

Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 23, 2013