Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis
This study is currently recruiting participants.
Verified June 2017 by Wonder Drake, Vanderbilt University
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Wonder Drake, Vanderbilt University
First received: December 26, 2013
Last updated: June 27, 2017
Last verified: June 2017
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.
Sarcoidosis; Antimycobacterial Therapy
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
Primary Outcome Measures:
- Determine the effect of CLEAR therapy versus placebo on the 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. [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
Secondary Outcome Measures:
- Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . [ Time Frame: Baseline and 16 weeks ]
- Change in 6 minute walk distance, oxygen saturation and level of dyspnea [ Time Frame: Baseline, 4, 8 and 16 weeks ]
Outcome measure if a composite
- Change in the Saint George's Respiratory Questionnaire (SGRQ; King's Sarcoidosis Questionnaire (KSQ) for the assessment of health status; The Fatigue Assessment Scale (FAS). [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
Outcome measure if a composite
- Safety profile of regimen as evidenced by adverse events and abnormal lab values, tolerability and toxicity of the treatment regimen including comparison of reported adverse events and abnormal laboratory values compared to placebo. [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
- Change in FEV1 [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ]
- Failure of standard Therapy [ Time Frame: Baseline, 4, 8, and 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.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||March 2019 (Final data collection date for primary outcome measure)
Active Comparator: Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin
Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD
Other Name: Levaquin
Other Name: Z-pack
Other Name: Rifadin, Rimactane
Placebo Comparator: 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.
This will serve as a placebo to the antibiotics used in antimycobacterial therapy.
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.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
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.
- 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02024555
|Albany Medical Center
|Albany, New York, United States, 12208 |
|Contact: Marc Judson, MD 518-262-0355 email@example.com |
|Sub-Investigator: Marc Judson, MD |
|University of Cincinnati
|Cincinnati, Ohio, United States, 45267 |
|Principal Investigator: Robert Baughman, MD |
|Cleveland, Ohio, United States, 44195 |
|Contact: Dan Culver, DO |
|Principal Investigator: Dan Culver, DO |
|Ohio State University
|Columbus, Ohio, United States, 43221 |
|Contact: Elliott Crouser, M.D. 614-293-4925 firstname.lastname@example.org |
|Contact: Karen Martin 614-293-4978 email@example.com |
|Sub-Investigator: Elliott Crouser, M.D. |
|Medical University of South Carolina
|Charleston, South Carolina, United States, 29425 |
|Contact: James Ennis, MD 843-792-3769 firstname.lastname@example.org |
|Sub-Investigator: James Ennis, MD |
|Vanderbilt University School of Medicine
|Nashville, Tennessee, United States, 37232 |
|Contact: Wonder Drake, MD 615-322-2035 email@example.com |
|Principal Investigator: Wonder Drake, MD |
National Heart, Lung, and Blood Institute (NHLBI)
||Wonder Drake, MD
||Vanderbilt University School of Medicine
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on September 19, 2017
Lung Diseases, Interstitial
Respiratory Tract Diseases
Anti-Infective Agents, Urinary
Topoisomerase II Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers