Terbinafine Treatment of Axial Spondyloarthropathy

Study Overview
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Brief Summary
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This is a pilot study to determine if further research is warranted to assess if anti-fungal therapy is an effective adjunctive treatment for axial spondyloarthropathy

Detailed Description
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The purpose of this trial is to determine if terbinafine is an effective therapy for ankylosing spondylitis. Benefit will be determined by a reduction of the BASDAI by two or more. The primary endpoint is the BASDAI at the completion of 16 weeks of terbinafine versus the BASDAI at the start of the trial and at the completion of the placebo. The secondary endpoint with the percent of patients whose BASDAI improves by two or more while on terbinafine (week 16) versus the percent of subjects with a similar improvement after 16 weeks of placebo.

Official Title
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Terbinafine Treatment of Axial Spondyloarthropathy

Conditions
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Ankylosing Spondylitis, Axial Spondyloarthritis, Psoriatic Spondylitis, Spondylitis Secondary to Inflammatory Bowel Disease, Axial Spondyloarthopathy

Intervention / Treatment
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* Drug: Terbinafine Tablets
* Diagnostic Test: Laboratory Testing
* Diagnostic Test: Laboratory Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects age 18 and older of either sex will be included. Subjects must be willing and able to provide informed consent. Subjects must have been diagnosed with ankylosing spondylitis, axial spondyloarthritis, psoriatic spondylitis or spondylitis secondary to inflammatory bowel disease by a physician and must be willing to request records to validate the diagnosis. Subjects must complete a symptom questionnaire called a BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and must have a score of four or above to indicate active disease and the potential to improve. Subjects must agree to remain on a stable treatment regimen for their joint disease for the duration of the trial and for one month before the study begins. Subjects must be willing to provide stool samples and be willing to have routine lab studies every 8 weeks during the duration of the study. Exclusion Criteria: Pregnant or lactating women will not be included. Subjects must not be allergic or intolerant to terbinafine. Subjects must not be taking medications that have the potential for serious interactions with terbinafine. These drugs include desipramine, cimetidine, fluconazole, cyclosporine and rifampin. Subjects must not have taken antibiotics within 3 months of starting the study drug and collecting the baseline stool specimen. Subjects with the following blood dyscrasias will not be included: Hemoglobin <9g/dL or Hematocrit <30% White blood cell count <3.0 K/cu mm Absolute neutrophil count <1.2 K/cu mm Platelet count <100 K/cu mm Subjects with an estimated GFR ≤50 ml/min Subjects with a total bilirubin, AST, or ALT more than 1.5 times the upper limit of normal at screening. Severe, progressive, or uncontrolled chronic liver disease including fibrosis, cirrhosis, or recent or active hepatitis. History of any lymphoproliferative disorder such as Epstein Barr virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggest of current lymphatic disease. Current malignancy or history of malignancy, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ. Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis and aspergilloma, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening. Have a known infection with human immunodeficiency virus (HIV) Have current signs and symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac (New York Heart Association class III or IV), neurologic, or cerebral diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects will receive either terbinafine 500 mg or placebo for 16 weeks and then crossed over to the opposite therapy for another 16 weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo to Drug<br>Subjects will begin treatment on placebo then crossover to study drug. | Drug: Terbinafine Tablets<br>* 500mg oral terbinafine or placebo daily<br>* Other names: Lamisil;Diagnostic Test: Laboratory Testing<br>* Laboratory testing at screening, baseline, week 8, 16, 24 and 32.<br>* Other names: Blood work;Diagnostic Test: Laboratory Testing<br>* Subjects with the potential to become pregnant will have a baseline urine pregnancy test prior to starting study drug.<br>* Other names: Urinalysis;|
| Active Comparator: Drug to Placebo<br>Subjects will begin treatment on study drug then crossover to placebo. | Drug: Terbinafine Tablets<br>* 500mg oral terbinafine or placebo daily<br>* Other names: Lamisil;Diagnostic Test: Laboratory Testing<br>* Laboratory testing at screening, baseline, week 8, 16, 24 and 32.<br>* Other names: Blood work;Diagnostic Test: Laboratory Testing<br>* Subjects with the potential to become pregnant will have a baseline urine pregnancy test prior to starting study drug.<br>* Other names: Urinalysis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BASDAI score | BASDAI score after the completion of 16 weeks of terbinafine treatment versus the BASDAI score after 16 weeks on placebo. Benefit is defined by a reduction of BASDAI score of 2 or more. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fungus, malassezia, microbiome