Trial of Antimycobacterial Therapy in Sarcoidosis

Sarcoidosis Clinical Trial

— CLEAR  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01074554
• Other study ID #: 091103
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: February 8, 2010
• Last updated: December 16, 2010
• Start date: February 2010
• Est. completion date: February 2011

Study information

• Verified date: December 2010
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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. We hypothesize that sarcoidosis pathogenesis reflects an immune response against metabolically-active mycobacterial species. The purpose of this study is to assess if administration of anti-mycobacterial drug therapy will aid in resolution of cutaneous sarcoidosis lesions.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 32
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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, biopsy finding granulomas, and no alternative for the cause of the granulomas, such as tuberculosis

2. Patients must have chronic cutaneous skin lesions with or without taking chronic therapy (corticosteroids, methotrexate (max 10mg/week), azathioprine, hydroxychloroquine, cyclophosphamide, minocycline, doxycycline and chloroquine), in which the dose has not been altered in the 2 months prior to starting the study.

3. Subject has a diagnosis of cutaneous sarcoidosis for greater than 6 months with a Sarcoidosis Activity and Severity Index assessment score of at least 4. Diagnosis can be made by either:

• Skin lesions characteristic of sarcoidosis and a biopsy showing granulomas with no evidence of mycobacteria, fungus, or malignancy.

• A biopsy that does not show granulomas, but the patient has characteristic skin lesions and history of clinical features suggesting sarcoidosis (previous biopsy revealing noncaseating granuloma, bilateral hilar adenopathy, erythema nodosum, uveitis, raised ACE level, BAL lymphocytosis (CD4:CD8>3.5), panda/lambda sign on gallium scan)

• Accepted clinical variants include, but are not necessarily limited to the following:

• lupus pernio

• nodular

• subcutaneous

• annular

• angiolupoid

• plaque

• papular

• lichenoid

• psoriasiform

• For purposes of this study "moderate to severe cutaneous sarcoidosis" is defined as the presence of sarcoidal skin lesions with any of the following features:

• At least 5 easily visible facial lesions, or

• Disease which involves > 3% BSA, or

• Disease which confers functional impairment (e.g. nasal or visual field obstruction), or

• Disease which confers significant symptoms of itching and/or pain.

4. 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 serum pregnancy test at screening visit.

Exclusion Criteria:

1. No consent/inability to obtain consent.

2. Age less than 18 years of age.

3. Inability to obtain biopsy or draw blood.

4. CPK, ALT or AST >5 times upper limit of normal (ULN)

5. Pregnancy or breast feeding.

6. Current use of medications metabolized by rifampin (See Appendix).

7. Allergy to macrolides, quinolones or rifamycins.

8. Visual Impairment as defined by differentiating colors.

9. Family or personal history of long QT syndromes.

10. Patients receiving another interventional investigational drug within the 30 days prior to dosing

11. Use of any investigational medication within the past 28 days prior to study enrollment.

12. Subject has been hospitalized for infection or received IV antibiotics within the previous 2 months prior to baseline.

13. 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.

14. Evidence of other active skin diseases or skin infections during screening that may interfere with evaluation of sarcoidosis.

15. Subject has an active infection requiring systemic antibiotics at time of screening

16. Subject has a history of listeriosis, treated or untreated tuberculosis, exposure to individuals with tuberculosis.

17. Subject has a variant of sarcoidosis that is not amenable to study evaluation, in the absence of chronic indurated lesions, such as:

• Acute, "benign" sarcoid associated with erythema nodosum

• Acute iritis

• Ichthyosiform sarcoidosis

• Hypo- or hyperpigmented macular sarcoidosis

• Ulcerative sarcoidosis

• Erythroderma

• Alopecia

18. Patients otherwise unsuitable for participation in the opinion of the investigator

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Sarcoidosis

Intervention

Drug:
• antibiotics
Levaquin 750 mg loading on day 1, then 500 mg po QD Ethambutol 15-25 mg/kg for a maximum of 1200mg QD Azithromycin 500mg on day 1, then 250 mg po QD Rifampin 5-10 mg/kg for a maximum of 300mg po QD
• lactose
lactose control tablets; one for each antibiotic with equivalent pills

Locations

Country	Name	City	State
United States	Vanderbilt University School of Medicine	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		8 weeks	No
Secondary	Decrease in the quantitative copies of mycobacterial DNA in sarcoidosis lesions		8 weeks	No
Secondary	Decrease in mycobacteriophage titer isolation from biopsy specimens		8 weeks	No
Secondary	Decrease in peripheral and granulomatous T cell response to mycobacterial antigens.		8 weeks	No
Secondary	Dichotomous endpoints regarding change in lesion size after completion of therapy		8 weeks	No
Secondary	3 point or greater change in Sarcoidosis Activity and Severity Index(SASI) at completion of therapy.		8 weeks	No