The Effect of N-Acetyl-L-Cysteine, on Inflammatory and Oxidative Stress Markers in Pulmonary Sarcoidosis

The Effect of an Oral Antioxidant, N-Acetyl-L-Cysteine, on Inflammatory and Oxidative Stress Markers in Pulmonary Sarcoidosis

This is a pilot study investigating the effect of an antioxidant, N-Acetyl-L-Cysteine (NAC), on inflammation and oxidative stress in sarcoidosis.

Study Overview

• Status: Completed
• Conditions: Pulmonary Sarcoidosis
• Intervention / Treatment: Dietary supplement: N-acetyl-cysteine; Drug: Placebo

Detailed Description

Sarcoidosis is a granulomatous lung disease predominantly affecting the lungs. Reactive oxidative species are produced secondary to oxidative stress and inflammation and can affect key cellular processes. The investigators have shown a role for oxidative stress in chronic beryllium disease (CBD), a granulomatous disease that resembles sarcoidosis, and have also shown that antioxidant therapy reduces inflammation in CBD. Oxidative stress also plays a role in sarcoidosis but the exact mechanism and potential effect of antioxidant therapy on sarcoidosis is unknown. The investigators propose conducting a pilot study investigating the effect of an antioxidant, N-Acetyl-L-Cysteine (NAC), on inflammation and oxidative stress in sarcoidosis. The investigators will measure and compare markers of inflammation and oxidative stress in the lungs of sarcoidosis patients before and after treatment with NAC. The results of this study will prepare the investigators for a larger study investigating the role of NAC as a therapy for sarcoidosis with changes in lung function and x-ray as our primary outcome. This will provide the investigators with a new non-toxic therapy for sarcoidosis that can be used on its own or to supplement other therapies minimizing their toxicity.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biopsy proven sarcoidosis.
• Pulmonary parenchymal involvement with a Scadding chest x-ray stage II, III or IV.
• Abnormal spirometry and/or DLCO (< 80% of predicted).
• Consenting adults : Age 18 years and above

Exclusion Criteria:

• Positive lung washing or biopsy cultures for fungi or mycobacterial disease;
• Presence of other co-morbid conditions that may affect the patient's outcome.
• Patient inability to undergo venipuncture and BAL procedures.
• Current use of tobacco (smoking or otherwise) in the past 6 months
• Treatment with immunosuppressive therapy within the past 6 months.
• On oral anti-oxidant supplements.
• Active peptic ulcer disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral N-acetyl-cysteine; oral NAC 900mg three times daily for 8 weeks	Dietary supplement: N-acetyl-cysteine; 900mg three times daily for 8 weeks
Placebo Comparator: Matching Placebo; oral placebo three times daily for 8 weeks	Drug: Placebo; Matching placebo three times daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels	Baseline peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) lymphocyte percentages and lipopolysaccharide (LPS) stimulated tumor necrosis factor-α levels (pg/ml)	8 weeks of anti-oxidant therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels	We measured changes at baseline and at 8 weeks in BAL whole cell total GSH levels and cellular 8-OHdG before and after treatment with NAC/placebo.	8 weeks of anti-oxidant therapy

Collaborators and Investigators

• Sponsor: National Jewish Health
• Collaborators: American Thoracic Society
• Investigators: Principal Investigator: Nabeel Hamzeh, MD, National Jewish Health

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: January 10, 2012
• First Submitted That Met QC Criteria: April 26, 2012
• First Posted (Estimate): April 27, 2012

Study Record Updates

• Last Update Posted (Actual): November 4, 2020
• Last Update Submitted That Met QC Criteria: October 14, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: oxidative stress; Sarcoidosis; anti-oxidant
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Sarcoidosis, Pulmonary; Sarcoidosis; 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: 22219201

Plan for Individual participant data (IPD)

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