Terbinafine Treatment of Axial Spondyloarthropathy

NCT05119712 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: STUDY00021565
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Ankylosing Spondylitis; Axial Spondyloarthritis; Psoriatic Spondylitis; Spondylitis Secondary to Inflammatory Bowel Disease; Axial Spondyloarthopathy

Keywords

fungus, malassezia, microbiome

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Placebo to Drug

ACTIVE COMPARATOR

Subjects will begin treatment on placebo then crossover to study drug.

Drug: Terbinafine Tablets; Diagnostic Test: Laboratory Testing

Drug to Placebo

ACTIVE COMPARATOR

Subjects will begin treatment on study drug then crossover to placebo.

Drug: Terbinafine Tablets; Diagnostic Test: Laboratory Testing

Interventions

Terbinafine Tablets DRUG

500mg oral terbinafine or placebo daily

Also known as: Lamisil

Drug to Placebo; Placebo to Drug

Laboratory Testing DIAGNOSTIC_TEST

Laboratory testing at screening, baseline, week 8, 16, 24 and 32.

Also known as: Blood work

Drug to Placebo; Placebo to Drug

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oregon Health and Science University: lead
• The Malassezia Foundation: collaborator

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (14)

• Reveille JD, Witter JP, Weisman MH. Prevalence of axial spondylarthritis in the United States: estimates from a cross-sectional survey. Arthritis Care Res (Hoboken). 2012 Jun;64(6):905-10. doi: 10.1002/acr.21621. Epub 2012 Jan 24.

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• Goie The HS, Steven MM, van der Linden SM, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br J Rheumatol. 1985 Aug;24(3):242-9. doi: 10.1093/rheumatology/24.3.242.

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• Asquith M, Rosenbaum JT. The interaction between host genetics and the microbiome in the pathogenesis of spondyloarthropathies. Curr Opin Rheumatol. 2016 Jul;28(4):405-12. doi: 10.1097/BOR.0000000000000299.

  PMID: 27152700 BACKGROUND

• Laurence M, Asquith M, Rosenbaum JT. Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall-King Hypothesis. Front Med (Lausanne). 2018 Apr 5;5:80. doi: 10.3389/fmed.2018.00080. eCollection 2018.

  PMID: 29675414 BACKGROUND

• Mielants H, Veys EM, De Vos M, Cuvelier C, Goemaere S, De Clercq L, Schatteman L, Elewaut D. The evolution of spondyloarthropathies in relation to gut histology. I. Clinical aspects. J Rheumatol. 1995 Dec;22(12):2266-72.

  PMID: 8835560 BACKGROUND

• Maillet J, Ottaviani S, Tubach F, Roy C, Nicaise-Rolland P, Palazzo E, Dieude P. Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthritis: Prevalence and associated phenotype. Joint Bone Spine. 2016 Dec;83(6):665-668. doi: 10.1016/j.jbspin.2015.10.011. Epub 2016 Mar 15.

  PMID: 26992953 BACKGROUND

• Gross O, Gewies A, Finger K, Schafer M, Sparwasser T, Peschel C, Forster I, Ruland J. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature. 2006 Aug 10;442(7103):651-6. doi: 10.1038/nature04926. Epub 2006 Jul 12.

  PMID: 16862125 BACKGROUND

• Zhernakova A, Festen EM, Franke L, Trynka G, van Diemen CC, Monsuur AJ, Bevova M, Nijmeijer RM, van 't Slot R, Heijmans R, Boezen HM, van Heel DA, van Bodegraven AA, Stokkers PC, Wijmenga C, Crusius JB, Weersma RK. Genetic analysis of innate immunity in Crohn's disease and ulcerative colitis identifies two susceptibility loci harboring CARD9 and IL18RAP. Am J Hum Genet. 2008 May;82(5):1202-10. doi: 10.1016/j.ajhg.2008.03.016. Epub 2008 Apr 24.

  PMID: 18439550 BACKGROUND

• Pointon JJ, Harvey D, Karaderi T, Appleton LH, Farrar C, Stone MA, Sturrock RD, Brown MA, Wordsworth BP. Elucidating the chromosome 9 association with AS; CARD9 is a candidate gene. Genes Immun. 2010 Sep;11(6):490-6. doi: 10.1038/gene.2010.17. Epub 2010 May 13.

  PMID: 20463747 BACKGROUND

• Ruutu M, Thomas G, Steck R, Degli-Esposti MA, Zinkernagel MS, Alexander K, Velasco J, Strutton G, Tran A, Benham H, Rehaume L, Wilson RJ, Kikly K, Davies J, Pettit AR, Brown MA, McGuckin MA, Thomas R. beta-glucan triggers spondylarthritis and Crohn's disease-like ileitis in SKG mice. Arthritis Rheum. 2012 Jul;64(7):2211-22. doi: 10.1002/art.34423.

  PMID: 22328069 BACKGROUND

• Takahata Y, Sugita T, Hiruma M, Muto M. Quantitative analysis of Malassezia in the scale of patients with psoriasis using a real-time polymerase chain reaction assay. Br J Dermatol. 2007 Oct;157(4):670-3. doi: 10.1111/j.1365-2133.2007.08090.x. Epub 2007 Jul 19.

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• Limon JJ, Tang J, Li D, Wolf AJ, Michelsen KS, Funari V, Gargus M, Nguyen C, Sharma P, Maymi VI, Iliev ID, Skalski JH, Brown J, Landers C, Borneman J, Braun J, Targan SR, McGovern DPB, Underhill DM. Malassezia Is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Models. Cell Host Microbe. 2019 Mar 13;25(3):377-388.e6. doi: 10.1016/j.chom.2019.01.007. Epub 2019 Mar 5.

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• Babu PR, Pravin AJS, Deshmukh G, Dhoot D, Samant A, Kotak B. Efficacy and Safety of Terbinafine 500 mg Once Daily in Patients with Dermatophytosis. Indian J Dermatol. 2017 Jul-Aug;62(4):395-399. doi: 10.4103/ijd.IJD_191_17.

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• Chapman SW, Pappas P, Kauffmann C, Smith EB, Dietze R, Tiraboschi-Foss N, Restrepo A, Bustamante AB, Opper C, Emady-Azar S, Bakshi R. Comparative evaluation of the efficacy and safety of two doses of terbinafine (500 and 1000 mg day(-1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis. Mycoses. 2004 Feb;47(1-2):62-8. doi: 10.1046/j.1439-0507.2003.00953.x.

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MeSH Terms

Conditions

Spondylitis, Ankylosing; Axial Spondyloarthritis

Interventions

Terbinafine; Clinical Laboratory Techniques; Urinalysis

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Clinical Chemistry Tests; Diagnostic Techniques, Urological

Study Officials

• Atul Deodhar, M.D.

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Subjects will receive either terbinafine 500 mg or placebo for 16 weeks and then crossed over to the opposite therapy for another 16 weeks.

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 15, 2021
• Study Start: March 9, 2021
• Primary Completion: October 15, 2023
• Study Completion: October 15, 2024
• Last Updated: August 28, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)