Clinical trial NCT02024555: Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis
Official title: Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoidosis; Antimycobacterial Therapy
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-12-31
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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 demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
2. 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.
3. Possess evidence of parenchymal or nodal disease on chest radiograph.

Exclusion Criteria:

1. Inability to obtain consent
2. Age less than 18 years
3. 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
4. FVC predicted value is \< 45%.
5. End-stage fibrotic pulmonary disease.
6. Significant underlying liver disease.
7. Allergy or intolerance to any of the antibiotics within the CLEAR regimen.
8. Allergy or intolerance to albuterol
9. Poor venous access for obtaining blood samples
10. 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.
11. Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure disorders)
12. Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer.
13. Currently receiving \>40mg prednisone.
14. ALT or AST \>5 times upper limit of normal (ULN)
15. Leukopenia, as defined by WBC \<3.0 cells/mm3 or absolute neutrophil count \<1000
16. Breast feeding.
17. 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.
18. If patient is on immunomodulators, they must be on regimen for ≥ 3-month period and on a stable dose for \> 4 weeks.
19. Family or personal history of long QT interval
20. Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction \<35%
21. 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.
22. 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.
23. On medications that interact with the antibiotics of the CLEAR regimen
24. History of or receiving treatment for pulmonary hypertension. Receiving biologic medication within the 6 months prior to screening visit

Primary outcomes:
measure: 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.
timeFrame: Baseline to 16 weeks
Secondary outcomes:
measure: Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .
timeFrame: Baseline and 16 weeks
measure: Six Minute Walk, Distance in Meters
timeFrame: Baseline, 4, 8, and 16 and 24 weeks
measure: Change in Oxygen Saturation
timeFrame: Baseline, 4, 8, and 16 and 24 weeks
measure: Change in Level of Dyspnea
timeFrame: Baseline, 4, 8 and 16 weeks
measure: Change in the Saint George's Respiratory Questionnaire (SGRQ)
timeFrame: Baseline and 16 weeks
measure: Fatigue Assessment Scale (FAS).
timeFrame: Baseline, 4, 8, 16 and 24 weeks
measure: Change in the King's Sarcoidosis Questionnaire (KSQ) for the Assessment of Health Status;
timeFrame: Baseline and 16 weeks
measure: Adverse Events
timeFrame: 24 weeks
measure: FEV1%
timeFrame: Baseline, 4, 8, and 16 and 24 weeks
measure: Failure of Standard Therapy
timeFrame: Baseline to 16 weeks
measure: Abnormal Lab Values
timeFrame: baseline to 16 weeks
Other outcomes:
Locations:
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
Study officials:
affiliation: Vanderbilt University School of Medicine
name: Wonder Drake, MD
role: PRINCIPAL_INVESTIGATOR
References: