Trimethoprim-Sulfamethoxazole for Wegener's Granulomatosis

(TEMPO Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Pennsylvania

Must not be taking: Antibiotics, Antifungals

Disqualifiers: Infection, Cocaine use, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the antibiotic trimethoprim-sulfamethoxazole to determine its effectiveness for individuals with granulomatosis with polyangiitis (GPA), a condition where the immune system attacks the body's tissues, particularly the nose and sinuses. The researchers aim to understand how this treatment affects nasal bacteria and fungi, as well as the body's immune response. Suitable participants have GPA with a history of nasal issues, are currently stable on their medications, and have not recently used antibiotics. The study involves nasal swabs and an optional blood draw over six months to collect data. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that trimethoprim-sulfamethoxazole is likely to be safe for humans?

Research shows that the medication trimethoprim-sulfamethoxazole (TMP-SMX) is generally safe for individuals with granulomatosis with polyangiitis (GPA), an autoimmune disease. Studies have found that TMP-SMX can reduce the risk of relapses in GPA patients, indicating it is well-tolerated for this purpose.

TMP-SMX already has FDA approval for other uses, which provides some reassurance about its safety. However, like any medication, it can cause side effects, such as skin rashes, upset stomach, or changes in blood cell counts. Most people do not experience serious issues, but discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Wegener's?

Researchers are excited about trimethoprim-sulfamethoxazole for Wegener's Granulomatosis because it offers a potential alternative to the typical immunosuppressive drugs like cyclophosphamide and corticosteroids. This combination antibiotic treatment focuses on targeting and eliminating bacterial infections that might contribute to the disease's flare-ups, which is a different approach compared to the current standard therapies that primarily suppress the immune system. By potentially reducing the frequency and severity of flares without heavy immunosuppression, trimethoprim-sulfamethoxazole could lead to fewer side effects and improved quality of life for patients.

What evidence suggests that trimethoprim-sulfamethoxazole might be an effective treatment for Wegener's granulomatosis?

Research has shown that the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) can help reduce relapses in people with granulomatosis with polyangiitis (GPA), also known as Wegener's granulomatosis. In this trial, participants will receive TMP-SMX to evaluate its effectiveness in reducing disease flare-ups. This is crucial because GPA can cause serious inflammation and damage to multiple organs. The antibiotic may work by reducing harmful bacteria that could trigger the disease or by having anti-inflammatory effects. Although the exact mechanism remains unclear, evidence supports TMP-SMX as a helpful treatment for managing GPA. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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

I am taking 10mg or less of Prednisone daily.

I have been in remission for 3 months and will be on stable medication for the next 6 months, except for small changes in prednisone.

Patients with granulomatosis with polyangiitis (GPA) will be determined by specific classification criteria or by the doctor's assessment.

Exclusion Criteria

I am allergic to sulfa drugs, or have severe kidney or liver problems.

I have not used nasal antibiotics in the last 4 weeks.

I have not taken oral antibiotics or antifungals in the last 6 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trimethoprim-sulfamethoxazole (TMP-SMX) for 4 weeks to evaluate changes in the nasal microbiome, mycobiome, and host immunity

4 weeks

Weekly visits for nasal swab and cytobrush sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Monthly visits for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Trimethoprim Sulfamethoxazole

Trial Overview The TEMPO study is testing the effects of Trimethoprim-Sulfamethoxazole (TMP-SMX) on patients with GPA. It aims to understand changes in the nasal microbiome and host immunity by analyzing DNA from nasal swabs before, during, and after a 4-week TMP-SMX treatment period. The trial will follow each patient over six months.

How Is the Trial Designed?

Group I: On Drug Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8637536/

Trimethoprim-sulfamethoxazole (co-trimoxazole) for the ... Conclusions: Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission. Publication types. Clinical ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03919435

TEMPO Study: Trimethoprim-Sulfamethoxazole in ... Study Overview. Brief Summary. Granulomatosis with polyangiitis (GPA; Wegener's) is a multi-organ autoimmune disease characterized by necrotizing granulomatous ...

3. nejm.org nejm.org/doi/full/10.1056/NEJM199607043350103

Trimethoprim–Sulfamethoxazole (Co-Trimoxazole) for the ... The results of this study demonstrate that prolonged treatment with co-trimoxazole reduces the number of relapses in patients with Wegener's ...

4. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03114-7

Trimethoprim-sulfamethoxazole prophylaxis during treatment ... In conclusion, TMP-SMX was dispensed to less than one-third of US patients with GPA receiving RTX between 2011 and 2020. In our cohort, recent ...

5. academic.oup.com academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae368/7716551

Trimethoprim sulfamethoxazole prophylaxis and serious ... TMP-SMX prophylaxis was associated with reduced serious infections in rituximab-treated GPA, but may increase adverse events, warranting further study of ...

6. emedicine.medscape.com emedicine.medscape.com/article/332622-medication

Granulomatosis with Polyangiitis (GPA, formerly Wegener ... Data show that TMP-SMZ may be beneficial in decreasing relapses during maintenance therapy of GPA. Twice-daily dosing should not be combined ...