Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis
- Conditions
- Sarcoidosis; Antimycobacterial Therapy
- Interventions
- Registration Number
- NCT02024555
- Lead Sponsor
- Vanderbilt University
- Brief Summary
The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.
- Detailed Description
Primary Objective: To assess the efficacy and safety of oral CLEAR therapy in patients with confirmed progressive pulmonary sarcoidosis.
Hypothesis: The CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants by augmenting T cell responses through the normalization of p56Lck expression and IL-2 production.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 97
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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 demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
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Evidence of disease progression as defined by at least one of the following three criteria:
Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.
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Possess evidence of parenchymal or nodal disease on chest radiograph.
- Inability to obtain consent
- Age less than 18 years
- Female participants of childbearing potential not willing to use 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, non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Note: Oral contraceptive pills are not effective birth control when taking rifamycin. A negative urine pregnancy test at screening visit if female of childbearing potential
- FVC predicted value is < 45%.
- End-stage fibrotic pulmonary disease.
- Significant underlying liver disease.
- Allergy or intolerance to any of the antibiotics within the CLEAR regimen.
- Allergy or intolerance to albuterol
- Poor venous access for obtaining blood samples
- History of active tuberculosis, close contact with a person with active tuberculosis within the 6 months prior to the screening visit or has a positive PPD.
- Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure disorders)
- Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer.
- Currently receiving >40mg prednisone.
- ALT or AST >5 times upper limit of normal (ULN)
- Leukopenia, as defined by WBC <3.0 cells/mm3 or absolute neutrophil count <1000
- Breast feeding.
- Color perception impairment as defined by the inability to differentiate colors per personal history or history of optic neuritis from any cause, including from sarcoidosis.
- If patient is on immunomodulators, they must be on regimen for ≥ 3-month period and on a stable dose for > 4 weeks.
- Family or personal history of long QT interval
- Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35%
- Participant has persistent or active infection(s) requiring hospitalization or treatment with antibiotics, antiretrovirals, or antifungals within 30 days prior to baseline. Minocycline and doxycycline are not considered antibiotics when used to treat sarcoidosis.
- Any significant finding in the patient's medical history or physical or psychiatric exam prior to or after randomization that, in the opinion of the investigator, would affect patient safety or compliance or ability to deliver the study drug according to protocol.
- On medications that interact with the antibiotics of the CLEAR regimen
- History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen. Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin Levofloxacin Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin Ethambutol Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin Azithromycin Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin Rifampin Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD
- Primary Outcome Measures
Name Time Method Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy. Baseline to 16 weeks Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.
- Secondary Outcome Measures
Name Time Method FEV1% Baseline, 4, 8, and 16 and 24 weeks FEV1% was measure pre and post 6 minute walk test
Failure of Standard Therapy Baseline to 16 weeks We will assess how many subjects in either arm need escalation of their standard regimen (ie increase in prednisone) during the 16 weeks.
Change in Oxygen Saturation Baseline, 4, 8, and 16 and 24 weeks measured using pulse oximetry
Fatigue Assessment Scale (FAS). Baseline, 4, 8, 16 and 24 weeks The FAS is a 10-item general fatigue questionnaire to assess fatigue. Total scores can range from 10, indicating the lowest level of fatigue, to 50, denoting the highest.
Adverse Events 24 weeks Safety profile of regimen as evidenced by the number of adverse events
Change in the Saint George's Respiratory Questionnaire (SGRQ) Baseline and 16 weeks The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction.
Scores range from 0 to 100, with higher scores indicating more limitations.
A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing.Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray . Baseline and 16 weeks Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . Local investigators will score chest x-rays.
Six Minute Walk, Distance in Meters Baseline, 4, 8, and 16 and 24 weeks The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes.
Change in Level of Dyspnea Baseline, 4, 8 and 16 weeks Outcome measure if a composite
Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status; Baseline and 16 weeks The KSQ is a free, online questionnaire to be filled out by sarcoidosis patients. The questionnaire takes around 10 minutes and is split into 5 sections; general health status, lungs, medication, skin and eyes. There are 29 questions in total, however some questions may not be answered (depending on the type of sarcoidosis affected). Each question asks patients to rate how they feel about many different aspects of their life, for instance how much pain they are in or how difficult they find everyday tasks. Information provided is confidential. Results are given as a number between 1-100 with higher numbers indicating better health.
Abnormal Lab Values baseline to 16 weeks Safety profile of regimen as evidenced by the number of abnormal lab values classified as Adverse Events
Trial Locations
- Locations (6)
Ohio State University
🇺🇸Columbus, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Vanderbilt University School of Medicine
🇺🇸Nashville, Tennessee, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Albany Medical Center
🇺🇸Albany, New York, United States