Lung Function, Pulmonary Sarcoidosis
Conditions
Keywords
sarcoidosis, mycobacteria, lung, pulmonary, radiographic improvement
Brief summary
Sarcoidosis is a granulomatous disease for which the molecular and immunologic association with mycobacteria continues to strengthen. The investigators are interested in conducting a proof-of-concept investigation of the effects of antibiotics on sarcoidosis resolution. The investigators hypothesize that pulmonary sarcoidosis will improve faster if patients are given antimycobacterial therapy, in addition to their standard therapy.
Interventions
DRUGlevaquin; ethambutol; rifampin and azithromycin.
Levaquin 750 mg loading on day 1, then 500 mg po QD Ethambutol 15-25 mg/kg for a maximum of 1200mg po QD Azithromycin 500mg on day 1, then 250 mg po QD \*\*Rifampin 10 mg/kg for a maximum of 600mg po QD or Rifabutin 10 mg/kg for a maximum of 300 mg po QD. \*\*We will not use both, but either one or the other based upon if the patient is on other medications that are metabolized by the cytochrome P450 pathway.
Sponsors
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with sarcoidosis will be enrolled as defined below. 1. Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy finding granulomas, and no alternative for the cause of the granulomas, such as tuberculosis. 2. Evidence of parenchymal disease on chest radiograph (Stage II, III or IV) or Stage I disease by chest radiographs and evidence of abnormal spirometry. . Subjects with concurrent extrapulmonary sarcoidosis, particularly skin and eye involvement, can be enrolled. 3. FVC of \>=45% and \<=80% of predicted normal value at screening. 4. If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or is using one of the following methods of birth control for the duration of the study and 90 days after study completion: 1. condoms, sponge, foams, jellies, diaphragm, or intrauterine device 2. contraceptives (oral or parenteral) for three months prior to study drug administration 3. a vasectomized sole partner 4. Females of childbearing potential must have a negative urine pregnancy test at screening visit.
Exclusion criteria
* 1\. No consent/inability to obtain consent. 2. Age less than 18 years of age. 3. Inability to draw blood. 4. ALT or AST \>5 times upper limit of normal (ULN) 5. Pregnancy or breast feeding. 6. Allergy to macrolides, quinolones or rifamycins. 7. Visual Impairment as defined by differentiating colors per personal history. 8. Family or personal history of long QT syndromes. 9. Patients receiving another interventional investigational drug for sarcoidosis within the 30 days prior to dosing 10. Use of any investigational medication within the past 28 days prior to study enrollment. 11\. Subject has been hospitalized for infection or received IV antibiotics within the previous 2 months prior to baseline. 12\. Subject has a history of tuberculosis at anytime or close contact with a person with active tuberculosis within the previous 6 months, or persistent or active infections requiring hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV antifungals within 30 days of baseline, OR oral antibiotics, antivirals, or antifungals for purpose of treating infection, within 14 days of baseline. 13\. Subject has an active infection requiring systemic antibiotics at time of screening 14. Subject has a history of listeriosis, treated or untreated tuberculosis, exposure to individuals with tuberculosis. 15\. Have a diagnosis of other significant respiratory disorder other than sarcoidosis that would complicate the evaluation of response to treatment 16. Patients otherwise unsuitable for participation in the opinion of the investigator. 17\. No smoking for past one year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Absolute FVC From Baseline to Post Completion of 8 Weeks of Antibiotic Therapy. | 8 weeks | The primary endpoint was improvement in absolute FVC from baseline to completion of therapy. Spirometry testing was performed using a standardized calibrated laptop spirometer, Flowscreen II USA Spirometer (VIASYS Healthcare Inc., Yorba Linda, CA). The volume accuracy of the spirometer was checked daily using a three liter calibration syringe. Each subject was given at least three attempts and the greatest measurement for absolute FVC and Forced Expiratory Volume (FEV1) at baseline, four week, and eight week assessments was recorded. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from outpatient pulmonary clinics at Vanderbilt University Medical Center and the surrounding community between July 14 and August 24, 2010. All patients met American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Diseases (ATS/ERS/WASOG) criteria.
Participants by arm
| Arm | Count |
|---|---|
| Antibiotics Levaquin 750 mg loading on day 1, then 500 mg po QD Ethambutol 15-25 mg/kg for a maximum of 1200mg po QD Azithromycin 500mg on day 1, then 250 mg po QD
\*\*Rifampin 10 mg/kg for a maximum of 600mg po QD or Rifabutin 10 mg/kg for a maximum of 300 mg po QD. \*\*We will not use both, but either one or the other based upon if the patient is on other medications that are metabolized by the cytochrome P450 pathway. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 1 |
| Overall Study | Required antibiotic administration | 1 |
Baseline characteristics
| Characteristic | Antibiotics |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age Continuous | 54 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Change in Absolute FVC From Baseline to Post Completion of 8 Weeks of Antibiotic Therapy.
The primary endpoint was improvement in absolute FVC from baseline to completion of therapy. Spirometry testing was performed using a standardized calibrated laptop spirometer, Flowscreen II USA Spirometer (VIASYS Healthcare Inc., Yorba Linda, CA). The volume accuracy of the spirometer was checked daily using a three liter calibration syringe. Each subject was given at least three attempts and the greatest measurement for absolute FVC and Forced Expiratory Volume (FEV1) at baseline, four week, and eight week assessments was recorded.
Time frame: 8 weeks
Population: In the ITT analysis, we included the values from the last measured value for those who did not complete the trial. We analyzed the measured value at 8 weeks among those subjects who completed 8 weeks of therapy in the per protocol analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Antibiotics | Change in Absolute FVC From Baseline to Post Completion of 8 Weeks of Antibiotic Therapy. | 2.61 liters | Standard Deviation 1.01 |