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SarcoidosisPhase 1/2CLEARNCT01074554

Trial of Antimycobacterial Therapy in Sarcoidosis

A Phase 1/2 study testing Antibiotic Regimen in people with Sarcoidosis, run by Vanderbilt University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoidosis
What is being tested?
Antibiotic Regimen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteUnited States
Study dates
Feb 2010to Feb 2011
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • 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.

Who cannot join

  • 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).
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  • 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
  • Subject has a history of listeriosis, treated or untreated tuberculosis, exposure to individuals with tuberculosis.
  • 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
  • Patients otherwise unsuitable for participation in the opinion of the investigator

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Vanderbilt University School of Medicine

    Nashville, Tennessee, 37232

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Conditions
Sarcoidosis
Being tested
Antibiotic Regimen, Placebo Regimen
Keywords
sarcoidosis, mycobacteria, cutaneous lesions
Medical subject headings
Sarcoidosis, Mycobacterium Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Antibiotic RegimenDrug

    Also called Levaquin=Levofloxacin, Ethambutol=Myambutol, Azithromycin=Zithromax, Rifampin=Rifadin

    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

  • Placebo RegimenDrug

    Also called Lactose control tablets

    lactose control tablets; one for each antibiotic with equivalent pills

Study groups in NCT01074554
Study groupRoleWhat they receive
Antibiotic RegimenExperimentalThe 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.
Receives: Drug: Antibiotic Regimen
Placebo RegimenPlacebo comparatorThe placebo regimen consists of Lactose tablets, one for each antibiotic with equivalent pills
Receives: Drug: Placebo Regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline to 8 weeks

  2. Granuloma Burden

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

    Measured: Baseline to 8 weeks

Secondary outcomes (1)

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

    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).

    Measured: Baseline to 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionFeb 2011
  4. Study completionFeb 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01074554
Sponsor's protocol ID
091103
Acronym
CLEAR
Status last verified
Sep 2016
First submitted
8 Feb 2010
Last updated
12 Dec 2016
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23863960

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Antibiotic Regimen in people with Sarcoidosis, run by Vanderbilt University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01074554, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2016.

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