Trimethoprim-Sulfamethoxazole for Wegener's Granulomatosis
(TEMPO Trial)
Trial Summary
What is the purpose of this trial?
Granulomatosis with polyangiitis (GPA; Wegener's) is a multi-organ autoimmune disease characterized by necrotizing granulomatous inflammation and vasculitis. Upper respiratory involvement occurs in up to 90% of patients with GPA and is often the first manifestation of the disease. Patients with upper respiratory tract disease are more at risk of local and systemic relapse. Microbial organisms may be involved in inducing disease activity in GPA. Previous culture-dependent studies found that patients with GPA were more likely to be chronic nasal carriers of Staphylococcus aureus compared to non-GPA chronic rhinosinusitis and healthy controls; additionally, GPA patients with S. aureus colonization are more likely to experience a future relapse. This led to a randomized placebo-controlled trial of trimethoprim-sulfamethoxazole (TMP-SMX) which showed this antibiotic/antifungal was effective in preventing relapse in GPA. Whether the benefits of TMP-SMX are related to its antimicrobial properties versus anti-inflammatory effects is still unknown. The objective of this study is to prospectively evaluate the changes in the nasal microbiome, mycobiome, and host immunity in patients with GPA before, during, and after receipt of TMP-SMX for 4 weeks. The target enrollment number is 30 participants, and the investigators will include patients seen at the Penn Vasculitis Center with GPA (diagnosed according to the American College of Rheumatology Classification Criteria or based on investigator's judgment). To analyze nasal microbiome and host immunity, participants will be swabbed with nasal swab and cytobrush for DNA sequencing and other studies. An optional research blood draw is also included. The investigators and coordinators will follow each patient longitudinally over a 6-month period.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications, but you must not have taken oral antibiotics or antifungals in the past 6 weeks. You should also expect to stay on stable immunosuppressive therapies for the next 24 weeks, with only minor changes allowed to prednisone.
What data supports the effectiveness of the drug Trimethoprim-Sulfamethoxazole for treating Wegener's Granulomatosis?
Research shows that Trimethoprim-Sulfamethoxazole has been effective in treating Wegener's Granulomatosis, especially in cases resistant to other treatments, with patients experiencing significant improvement and remission. It has been used successfully as an alternative or additional treatment, often reducing the need for more toxic drugs.12345
Is trimethoprim-sulfamethoxazole generally safe for humans?
Trimethoprim-sulfamethoxazole is considered to have fewer side effects compared to other treatments for Wegener's granulomatosis, and it has been used successfully in patients with this condition. However, some patients may experience adverse reactions, but desensitization protocols can help manage these reactions.12356
How is the drug sulfamethoxazole-trimethoprim unique in treating Wegener's granulomatosis?
Sulfamethoxazole-trimethoprim is unique because it offers an alternative or additional treatment option for Wegener's granulomatosis, especially for patients who do not respond well to traditional cytotoxic agents like cyclophosphamide. It has fewer side effects and can be effective in achieving remission, sometimes even as the sole treatment, which is a significant advantage over more toxic therapies.12345
Eligibility Criteria
Adults diagnosed with Granulomatosis with Polyangiitis (GPA), who have been in remission for at least 3 months, and are expected to maintain stable immunosuppressive therapy. They must have had sinus issues due to GPA and be on a low dose of prednisone or equivalent. Excluded are those recently on antibiotics/antifungals, with HIV, severe kidney/liver issues, sulfa allergy, pregnancy plans within 6 months, recent nasal antibiotic use or cocaine use.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive trimethoprim-sulfamethoxazole (TMP-SMX) for 4 weeks to evaluate changes in the nasal microbiome, mycobiome, and host immunity
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Trimethoprim Sulfamethoxazole
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Pennsylvania
Lead Sponsor