Investigation of the Efficacy of Antibiotics on Pulmonary Sarcoidosis (CLEAR Lung)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Pulmonary Sarcoidosis Lung Function |
Drug: levaquin; ethambutol; rifampin and azithromycin. |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic |
| Official Title: | Investigation of the Efficacy of Antibiotics on Pulmonary Sarcoidosis |
- Change in Absolute FVC From Baseline to Post Completion of 8 Weeks of Antibiotic Therapy. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]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.
| Enrollment: | 15 |
| Study Start Date: | July 2010 |
| Study Completion Date: | November 2010 |
| Primary Completion Date: | November 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 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. |
Drug: levaquin; 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. |
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Subjects with sarcoidosis will be enrolled as defined below.
- 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.
- 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.
- FVC of >=45% and <=80% of predicted normal value at screening.
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:
- condoms, sponge, foams, jellies, diaphragm, or intrauterine device
- contraceptives (oral or parenteral) for three months prior to study drug administration
- a vasectomized sole partner
- 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.
Contacts and Locations| United States, Tennessee | |
| Vanderbilt University School of Medicine | |
| Nashville, Tennessee, United States, 37232 | |
| Principal Investigator: | Wonder P Drake, MD | Vanderbilt University School of Medicine |
More Information
No publications provided
| Responsible Party: | Wonder Drake, Associate Professor of Medicine, Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT01169038 History of Changes |
| Other Study ID Numbers: | 100552 |
| Study First Received: | July 22, 2010 |
| Results First Received: | September 17, 2012 |
| Last Updated: | October 26, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Vanderbilt University:
|
sarcoidosis mycobacteria lung pulmonary radiographic improvement |
Additional relevant MeSH terms:
|
Sarcoidosis Sarcoidosis, Pulmonary Lymphoproliferative Disorders Lymphatic Diseases Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Anti-Bacterial Agents Ethambutol Ofloxacin Rifampin Azithromycin |
Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antitubercular Agents Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Infective Agents, Urinary Renal Agents Antibiotics, Antitubercular Leprostatic Agents |
ClinicalTrials.gov processed this record on May 22, 2013