Investigation of the Efficacy of Antibiotics on Pulmonary Sarcoidosis

NCT01169038 | Completed Phase 1 Results DMC

• 1 other identifier: 100552
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pulmonary Sarcoidosis; Lung Function

Keywords

sarcoidosis; mycobacteria; lung; pulmonary; radiographic improvement

Outcome Measures

Primary Outcomes (1)

• Change in Absolute FVC From Baseline to Post Completion of 8 Weeks of Antibiotic Therapy.

  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.

  8 weeks

Study Arms (1)

Antibiotics

ACTIVE COMPARATOR

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.

Interventions

levaquin; ethambutol; rifampin and azithromycin. DRUG

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.

Antibiotics

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \. 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.
• \. Subject has been hospitalized for infection or received IV antibiotics within the previous 2 months prior to baseline.
• \. 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.
• \. 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.
• \. 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.
• \. No smoking for past one year.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Drake WP, Richmond BW, Oswald-Richter K, Yu C, Isom JM, Worrell JA, Shipley GR. Effects of broad-spectrum antimycobacterial therapy on chronic pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2013 Nov 25;30(3):201-11.

  PMID: 24284293 DERIVED

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis; Mycobacterium Infections

Interventions

Levofloxacin; Ethambutol; Rifampin; Azithromycin

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Results Point of Contact

• Title: Wonder Drake
• Organization: Vanderbilt University

wonder.drake@vanderbilt.edu

615-322-2035

Study Officials

• Wonder P Drake, MD

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 22, 2010
• First Posted: July 23, 2010
• Study Start: July 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: October 31, 2012
• Results First Posted: October 19, 2012

Record last verified: 2012-10

Locations

US (1)