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

• Sponsor: National Jewish Health (Other)
• Overall Status: Completed
• CT.gov ID: NCT01587001
• Collaborator: American Thoracic Society (Other)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Sarcoidosis	Dietary Supplement: N-acetyl-cysteine; Drug: Placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effect of an Oral Antioxidant, N-Acetyl-L-Cysteine, on Inflammatory and Oxidative Stress Markers in Pulmonary Sarcoidosis
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels [8 weeks of anti-oxidant therapy]

   Baseline peripheral blood mononuclear cells and bronchoalveolar lavage (BAL) lymphocyte percentages and lipopolysaccharide (LPS) stimulated tumor necrosis factor-α levels (pg/ml)

Secondary Outcome Measures

1. Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels [8 weeks of anti-oxidant therapy]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Jewish Health	Denver	Colorado	United States	80206

Sponsors and Collaborators

• National Jewish Health
• American Thoracic Society

Investigators

• Principal Investigator: Nabeel Hamzeh, MD, National Jewish Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Jewish Health
• ClinicalTrials.gov Identifier: NCT01587001
• Other Study ID Numbers: 22219201
• First Posted: Apr 27, 2012
• Last Update Posted: Nov 4, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by National Jewish Health: Sarcoidosis; oxidative stress; anti-oxidant
• Additional relevant MeSH terms: Sarcoidosis, Pulmonary; Sarcoidosis; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Arm/Group Title	Oral N-acetyl-cysteine	Matching Placebo
Arm/Group Description	N-acetyl-cysteine: 900mg three times daily for 8 weeks	Placebo: Matching placebo three times daily for 8 weeks.
Period Title: Overall Study
STARTED	14	3
COMPLETED	8	2
NOT COMPLETED	6	1

Baseline Characteristics

Arm/Group Title	Oral N-acetyl-cysteine	Matching Placebo	Total
Arm/Group Description	oral NAC 900mg three times daily for 8 weeks N-acetyl-cysteine: 900mg three times daily for 8 weeks	Placebo: Matching placebo three times daily for 8 weeks.	Total of all reporting groups
Overall Participants	11	3	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (9)	52 (13)	53 (11)
Sex: Female, Male (Count of Participants)
Female	5 45.5%	2 66.7%	7 50%
Male	6 54.5%	1 33.3%	7 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	11 100%	3 100%	14 100%
Region of Enrollment (participants) [Number]
United States	11 100%	3 100%	14 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral N-acetyl-cysteine	Matching Placebo
Arm/Group Description	N-acetyl-cysteine: 900mg three times daily for 8 weeks	Placebo: Matching placebo three times daily for 8 weeks.
Measure Participants	8	2
Mean baseline BAL cell TNF-a	40767 (25684)	39938 (12033)
Mean follow-up BAL cell TNF-a	45176 (17910)	25671 (12203)
Mean baseline PBMC cell TNF-a	2775 (2292)	637 (404)
Mean follow-up PBMC cell TNF-a	3387 (2481)	969 (135)

2. Secondary Outcome

Title	Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels
Description	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.
Time Frame	8 weeks of anti-oxidant therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral N-acetyl-cysteine	Matching Placebo
Arm/Group Description	oral NAC 900mg three times daily for 8 weeks N-acetyl-cysteine: 900mg three times daily for 8 weeks	Placebo: Matching placebo three times daily for 8 weeks.
Measure Participants	8	2
Baseline visit	5.93 (2.94)	9.39 (2.06)
8 week visit	9.42 (3.64)	4.28 (0.12)

Adverse Events

Arm/Group Title	Oral N-acetyl-cysteine		Matching Placebo
Arm/Group Description	N-acetyl-cysteine: 900mg three times daily for 8 weeks		Placebo: Matching placebo three times daily for 8 weeks.
All Cause Mortality
	Oral N-acetyl-cysteine		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oral N-acetyl-cysteine		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Oral N-acetyl-cysteine		Matching Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.