Clinical Trial: Trial of Antimycobacterial Therapy in Sarcoidosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I/II Study of the Effects of Antibiotics on Sarcoidosis Pathogenesis

Brief Summary: Growing research from independent laboratories provide an association between mycobacteria and sarcoidosis. More recent immunologic and molecular studies demonstrate immune responses to mycobacteria virulence factors. The purpose of this study is to assess if administration of anti-mycobacterial drug therapy will aid in resolution of cutaneous sarcoidosis lesions.

Detailed Summary: Independent molecular and immunologic investigations strengthen the association between mycobacterial antigens and sarcoidosis pathogenesis. Molecular analysis of sarcoidosis granulomas reveals the presence of Mycobacterium tuberculosis complex (MTB) DNA and proteins that are significantly absent from granulomatous controls. Mycobacterial DNA has been detected in cutaneous sarcoidosis lesions, in addition to systemic immune responses against mycobacterial antigens. Due to the association between sarcoidosis and mycobacterial antigens, we postulated that broad spectrum antimycobacterial therapy could lead to restoration of T cell function and clinical improvement of chronic cutaneous sarcoidosis lesions. We investigated the safety and efficacy of Concomitant Levofloxacin, Ethambutol, Azithromycin, and Rifampin (CLEAR) therapy among chronic cutaneous sarcoidosis subjects, with change in lesion diameter from baseline to completion of 8 weeks of therapy as the primary endpoint; we assessed for decreases in granuloma burden, if granulomas were evident upon histologic examination. Change in modified Sarcoidosis Activity Severity Index (SASI) was the secondary endpoint.
Sponsor: Vanderbilt University

Current Primary Outcome:

  • Change in Lesion Size at the Completion of Antibiotic Therapy, Measured on a Continuous Scale; Change Will be Determined by Change in Diameter of the Lesions [ Time Frame: Baseline to 8 weeks ]
  • Granuloma Burden [ Time Frame: Baseline to 8 weeks ]
    Number of patients with a decrease in Granuloma Burden (only in those patients having granulomas present at baseline biopsy)


Original Primary Outcome: Change in lesion size at the completion of antibiotic therapy, measured on a continuous scale; change will be determined by decrease in diameter of the lesions, as well as the number of granulomas [ Time Frame: 8 weeks ]

Current Secondary Outcome: Change in Modified Sarcoidosis Activity and Severity Index (SASI) at Completion of Therapy. [ Time Frame: Baseline to 8 weeks ]

Characterization of lesion severity was conducted using Modified Sarcoidosis Activity and Severity Index (SASI), measuring erythema, induration and desquamation. The modification was that the same scale was applied to any part of the body, instead of the face alone. The scale range is 0 (no problem) to 72 (very severe).


Original Secondary Outcome:

  • Decrease in the quantitative copies of mycobacterial DNA in sarcoidosis lesions [ Time Frame: 8 weeks ]
  • Decrease in mycobacteriophage titer isolation from biopsy specimens [ Time Frame: 8 weeks ]
  • Decrease in peripheral and granulomatous T cell response to mycobacterial antigens. [ Time Frame: 8 weeks ]
  • Dichotomous endpoints regarding change in lesion size after completion of therapy [ Time Frame: 8 weeks ]
  • 3 point or greater change in Sarcoidosis Activity and Severity Index(SASI) at completion of therapy. [ Time Frame: 8 weeks ]


Information By: Vanderbilt University

Dates:
Date Received: February 8, 2010
Date Started: February 2010
Date Completion:
Last Updated: October 27, 2016
Last Verified: September 2016