Pulmonary Sarcoidosis
Conditions
Keywords
Sarcoidosis, oxidative stress, anti-oxidant
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.
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.
Interventions
DIETARY_SUPPLEMENTN-acetyl-cysteine
900mg three times daily for 8 weeks
DRUGPlacebo
Matching placebo three times daily for 8 weeks.
Sponsors
American Thoracic Society
National Jewish Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral N-acetyl-cysteine oral NAC 900mg three times daily for 8 weeks
N-acetyl-cysteine: 900mg three times daily for 8 weeks | 11 |
| Matching Placebo Placebo: Matching placebo three times daily for 8 weeks. | 3 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insufficient samples to complete testing | 4 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Oral N-acetyl-cysteine | Matching Placebo |
|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 11 | 56 years STANDARD_DEVIATION 9 | 52 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants | 11 Participants | 3 Participants |
| Region of Enrollment United States | 14 participants | 11 participants | 3 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 3 |
| serious Total, serious adverse events | 0 / 11 | 0 / 3 |
Outcome results
Primary
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)
Time frame: 8 weeks of anti-oxidant therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral N-acetyl-cysteine | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean baseline BAL cell TNF-a | 40767 pg/ml | Standard Deviation 25684 |
| Oral N-acetyl-cysteine | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean follow-up BAL cell TNF-a | 45176 pg/ml | Standard Deviation 17910 |
| Oral N-acetyl-cysteine | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean baseline PBMC cell TNF-a | 2775 pg/ml | Standard Deviation 2292 |
| Oral N-acetyl-cysteine | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean follow-up PBMC cell TNF-a | 3387 pg/ml | Standard Deviation 2481 |
| Matching Placebo | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean follow-up PBMC cell TNF-a | 969 pg/ml | Standard Deviation 135 |
| Matching Placebo | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean baseline BAL cell TNF-a | 39938 pg/ml | Standard Deviation 12033 |
| Matching Placebo | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean baseline PBMC cell TNF-a | 637 pg/ml | Standard Deviation 404 |
| Matching Placebo | Bronchoalveolar Lavage (BAL) and Peripheral Blood Mononuclear Cells (PBMC) TNF-α Levels | Mean follow-up BAL cell TNF-a | 25671 pg/ml | Standard Deviation 12203 |
Secondary
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.
Time frame: 8 weeks of anti-oxidant therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oral N-acetyl-cysteine | Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels | Baseline visit | 5.93 nmol/mg protein | Standard Deviation 2.94 |
| Oral N-acetyl-cysteine | Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels | 8 week visit | 9.42 nmol/mg protein | Standard Deviation 3.64 |
| Matching Placebo | Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels | Baseline visit | 9.39 nmol/mg protein | Standard Deviation 2.06 |
| Matching Placebo | Bronchoalveolar Lavage (BAL) Cell Glutathione (GSH) Levels | 8 week visit | 4.28 nmol/mg protein | Standard Deviation 0.12 |