ROS Signaling in Endothelial Function

The vascular endothelium (inner lining of cells in blood vessels) normally prevents vasospasm and thrombosis by producing nitric oxide and other regulatory substances. In patients with atherosclerosis, endothelial function is impaired. Excess production of reactive oxygen species (free radicals) contribute to endothelial dysfunction in atherosclerosis, and some prior studies have shown a beneficial effect of antioxidant treatment on endothelial function in patients with coronary artery disease. On the other hand, reactive oxygen species may be required for normal endothelial function and antioxidant supplements failed to show a benefit in large clinical trials. The effect of antioxidant treatment on endothelial function in healthy subjects is unknown. The present study will test the hypothesis that scavenging reactive species might reduce endothelium-dependent vasodilation in healthy subjects.

The study is a randomized, double-blind, placebo-controlled crossover study. Participants will receive 2.4 grams of oral NAC or similar-appearing placebo during the first visit, and then will cross over to the alternative treatment (NAC or placebo) for the second and final visit. We will examine endothelial function before and after treatment on each visit.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: Placebo; Drug: N-acetylcysteine

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sex: Male and Female subjects.
2. Age range: 21-65 years old.
3. Disease status: No acute, chronic, or debilitating medical condition or use of prescribed medications.
4. Willingness and ability to provide written informed consent and the ability to understand, to participate and to comply with the study requirements.

Exclusion Criteria:

1. Women with a positive urine beta HCG pregnancy test and lactating women.
2. Blood pressure greater than 140/90 mmHg; serum LDL cholesterol greater than 160 mg/dl; fasting blood sugar greater than 110 mg/dl.
3. History of any cigarette smoking within one year of the study.
4. Clinical history of any acute, chronic, or debilitating medical condition, including liver disease and peptic ulcer disease.
5. Treatment with an investigational new drug within the last 30 days.
6. History of a psychological illness or condition such as to interfere with the subject's ability to understand the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: N-acetylcysteine	Drug: N-acetylcysteine; N-acetylcysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Brachial artery flow-mediated dilation	4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood markers of antioxidant capacity	4 hours

Collaborators and Investigators

• Sponsor: Boston University

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 26, 2016

Study Registration Dates

• First Submitted: December 19, 2009
• First Submitted That Met QC Criteria: December 21, 2009
• First Posted (Estimate): December 23, 2009

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: March 8, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: N-acetylcysteine; endothelium; reactive oxygen species; cell signaling
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: H-26547

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No