Trial of Antimycobacterial Therapy in Sarcoidosis

NCT01074554 | Completed Phase 1 Results DMC

• 1 other identifier: 091103
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcoidosis

Keywords

sarcoidosis; mycobacteria; cutaneous lesions

Outcome Measures

Primary Outcomes (2)

• 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

  Baseline to 8 weeks

• Granuloma Burden

  Number of patients with a decrease in Granuloma Burden (only in those patients having granulomas present at baseline biopsy)

  Baseline to 8 weeks

Secondary Outcomes (1)

• Change in Modified Sarcoidosis Activity and Severity Index (SASI) at Completion of Therapy.

  Baseline to 8 weeks

Study Arms (2)

Antibiotic Regimen

EXPERIMENTAL

The Antibiotic Regimen consists of Levaquin 750 mg loading on day 1, then 500 mg po QD and Ethambutol 15-25 mg/kg for a maximum of 1200mg QD and Azithromycin 500mg on day 1, then 250 mg po QD and Rifampin 5-10 mg/kg for a maximum of 300mg po QD. All four drugs are given concomitantly.

Drug: Antibiotic Regimen

Placebo Regimen

PLACEBO COMPARATOR

The placebo regimen consists of Lactose tablets, one for each antibiotic with equivalent pills

Drug: Placebo Regimen

Interventions

Antibiotic Regimen DRUG

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 All four drugs are given concomitanly

Also known as: Levaquin=Levofloxacin, Ethambutol=Myambutol, Azithromycin=Zithromax, Rifampin=Rifadin

Antibiotic Regimen

Placebo Regimen DRUG

lactose control tablets; one for each antibiotic with equivalent pills

Also known as: Lactose control tablets

Placebo Regimen

Eligibility Criteria

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

You may qualify if:

• 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
• 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.
• 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

You may not qualify if:

• No consent/inability to obtain consent.
• Age less than 18 years of age.
• Inability to obtain biopsy or draw blood.
• CPK, ALT or AST \>5 times upper limit of normal (ULN)
• Pregnancy or breast feeding.
• Current use of medications metabolized by rifampin (See Appendix).
• Allergy to macrolides, quinolones or rifamycins.
• Visual Impairment as defined by differentiating colors.
• Family or personal history of long QT syndromes.
• Patients receiving another interventional investigational drug within the 30 days prior to dosing
• 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.
• Evidence of other active skin diseases or skin infections during screening that may interfere with evaluation of sarcoidosis.
• Subject has an active infection requiring systemic antibiotics at time of screening

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Drake WP, Oswald-Richter K, Richmond BW, Isom J, Burke VE, Algood H, Braun N, Taylor T, Pandit KV, Aboud C, Yu C, Kaminski N, Boyd AS, King LE. Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study. JAMA Dermatol. 2013 Sep;149(9):1040-9. doi: 10.1001/jamadermatol.2013.4646.

  PMID: 23863960 DERIVED

MeSH Terms

Conditions

Sarcoidosis; Mycobacterium Infections

Interventions

Levofloxacin; Ethambutol; Azithromycin; Rifampin

Condition Hierarchy (Ancestors)

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; Erythromycin; Macrolides; Polyketides; Lactones; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Wonder Drake
• Organization: Vanderbilt University School of Medicine

wonder.drake@vanderbilt.edu

615-322-2035

Study Officials

• Wonder P Drake, MD

  Vanerbilt 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: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 8, 2010
• First Posted: February 24, 2010
• Study Start: February 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: December 12, 2016
• Results First Posted: October 27, 2016

Record last verified: 2016-09

Locations

US (1)