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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Zurich
ClinicalTrials.gov Identifier:
NCT01578395
First received: April 12, 2012
Last updated: December 5, 2012
Last verified: December 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 24, 2014