Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Vanderbilt University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Wonder Drake, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT02024555
First received: December 26, 2013
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Sarcoidosis; Antimycobacterial Therapy;
Drug: Levofloxacin
Drug: Ethambutol
Drug: Azithromycin
Drug: Rifampin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigation of the Efficacy of Antimycobacterial Therapy on Pulmonary Sarcoidosis Phase II Randomized, Double-blind, Placebo-controlled Trial

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic improvement in sarcoidosis lung disease by frontal chest x-ray . [ Time Frame: Baseline and 16 weeks ] [ Designated as safety issue: No ]
  • Change in 6 minute walk distance, oxygen saturation and level of dyspnea [ Time Frame: Baseline, 4, 8 and 16 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
  • Change in FEV1 [ Time Frame: Baseline, 4, 8, 16 and 24 weeks ] [ Designated as safety issue: No ]
  • Failure of standard Therapy [ Time Frame: Baseline, 4, 8, and 16 weeks ] [ Designated as safety issue: No ]
    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: 128
Study Start Date: March 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Levofloxacin
Other Name: Levaquin
Drug: Ethambutol Drug: Azithromycin
Other Name: Z-pack
Drug: Rifampin
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.

Drug: Placebo
This will serve as a placebo to the antibiotics used in antimycobacterial therapy.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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. Tuberculosis must be ruled out by negative histology and culture.
  • Diagnosis of pulmonary sarcoidosis was made at least 1 year prior to consent date.
  • Evidence of disease progression as defined by at least two of the following four criteria:

    1. Decline of absolute percent predicted of FVC (FVC>45% and <=90% of predicted value) or DLCO of at least 5% on serial measurements (DLCO range >35%, if measured);
    2. Radiographic progression in chest imaging on side by side comparison;
    3. Change in dyspnea score, as measured by Transition Dyspnea Index (TDI);
    4. Progression of pulmonary sarcoidosis necessitating an increase in anti-sarcoidosis therapy.
  • 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.

Exclusion Criteria:

  • • Inability to obtain consent

    • Age less than 18 years of age
    • If female, participant 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 or a vasectomized sole partner. Note: Oral contraceptive pills are not effective birth control when taking rifampin or rifabutin. Females of childbearing potential must have a negative urine pregnancy test at screening visit
    • End-stage fibrotic pulmonary disease
    • Significant underlying liver disease
    • 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 mm3
    • 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.
    • Family or personal history of long QT interval
    • Most recent nuclear medicine scan or echocardiogram (if done), demonstrating cardiac ejection fraction <35%
    • If patient is on immunomodulators, they must be on regimen for ≥3-month period and on a stable dose for ≥ 4 weeks.
    • Participant has 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. 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 interacts with the antibiotics of the CLEAR regimen (Listed in Appendix A)
    • History of or receiving treatment for pulmonary hypertension.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02024555

Contacts
Contact: Wonder Drake, MD 615-322-2035 wonder.drake@vanderbilt.edu

Locations
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Principal Investigator: Robert Baughman, MD         
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Dan Culver, DO         
Principal Investigator: Dan Culver, DO         
United States, Tennessee
Vanderbilt University School of Medicine Recruiting
Nashville, Tennessee, United States, 37232
Contact: Wonder Drake, MD    615-322-2035    wonder.drake@vanderbilt.edu   
Principal Investigator: Wonder Drake, MD         
Vanderbilt University Medical Cener Recruiting
Nashville, Tennessee, United States
Contact: Wonder Drake    615-322-2035    wonder.drake@vanderbilt.edu   
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Wonder 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: NCT02024555     History of Changes
Other Study ID Numbers: R01 HL117074, R01HL117074-01
Study First Received: December 26, 2013
Last Updated: August 15, 2014
Health Authority: United States: Data and Safety Monitoring Board

Additional relevant MeSH terms:
Sarcoidosis
Sarcoidosis, Pulmonary
Lymphoproliferative Disorders
Lymphatic Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Bacterial Agents
Ethambutol
Levofloxacin
Ofloxacin
Rifampin
Azithromycin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Anti-Infective Agents, Urinary
Renal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antibiotics, Antitubercular
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 25, 2014