Testing the Role of Anti-fungal Therapy in Improving the Response to Therapies for Crohn's Disease
- Conditions
- Inflammatory Bowel DiseasesCrohn's Disease
- Interventions
- Registration Number
- NCT06274554
- Lead Sponsor
- Weill Medical College of Cornell University
- Brief Summary
The goal of this clinical trial is to learn about the effects of fluconazole in patients who plan to start or are currently undergoing standard of care treatment and plan to dose-escalate an IL-23 therapy for their Crohn's disease.
The main question it aims to assess is whether or not patient response to IL-23 therapies improve when simultaneously treated with fluconazole.
- Detailed Description
The purpose of this study is to examine the efficacy and safety of fluconazole in combination with IL-23 therapy versus IL-23 therapy alone for the treatment of Crohn's disease (CD). IL-23 therapy may include ustekinumab (anti-interleukin-12/23) or risankizumab (anti-interleukin-23).
Subjects will be stratified into two groups based on standard of care treatment: IL-23 therapy initiation or IL-23 therapy dose escalation. Subjects in each group will then be randomized to one of two treatment arms:
1. IL-23 Therapy with Fluconazole (200 mg on Day 0 and 100 mg on Days 1-13)
2. IL-23 Therapy with Placebo (200 mg on Day 0 and 100 mg on Days 1-13)
Subjects will blindly receive the fluconazole treatment only if they meet all inclusion and exclusion criteria. Subjects will return for standard of care clinic visits 2 weeks post-treatment initiation and 12 weeks post-treatment initiation. Disease activity will be assessed at standard of care visits. Stool and blood samples will collected for research from subjects at Day 0 (pre-treatment initiation), Week 2 post-treatment initiation, Week 8 post-treatment initiation, and Week 12 post-treatment initiation. If subjects consent to biopsies, biopsies will also be collected for research at endoscopic procedures (colonoscopies and/or flexible sigmoidoscopies). Subjects will return at Week 24 and 1 year post-treatment initiation for standard of care visits, where blood and stool will also be collected for research.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
-
Patients at least 18 years old
-
Patients with mild to moderate Crohn's disease as defined by CDAI score of 150-450
-
Besides the biologics of interest in this study, subjects must be on stable dosing of any therapy for at least 4 weeks prior to treatment initiation. Including:
- Steroids (9 mg or less of budesonide, 20 mg or less of prednisone)
- Mesalamines
- Immunomodulators
- Biologics
- Other medications for IBD (inflammatory bowel disease)
- Antibiotic usage within one month prior to initiation of blinded fluconazole usage
- Antifungal usage within one month prior to initiation of blinded fluconazole usage
- Known allergy to fluconazole
- Patients with known hepatic disease, cirrhosis, or with elevated liver biochemistries (e.g., transaminase(s) >3X upper limit of normal (ULN), and/or bilirubin levels >1.5X ULN (with exception of confirmed Gilbert's disease) at baseline
- Patients taking medications known to interact with fluconazole and cause serious adverse events, including but not limited to death, cardiac events, serious cardiac dysrhythmias, and prolongation of QTc (corrected QT interval)
- Pregnant or lactating women
- Severe Crohn's disease defined by a PRO-2 score ≥ 34 (patient reported outcomes) or imminent need for surgery, or deemed not medically fit by physician
- Patient with symptomatic stricturing
- Patient with pouchitis or an ostomy
- Patients with known, active fungal, or other, infection(s) since these patients would require particular, standard-of-care monitoring and treatment, which may include intravenous and/or prolonged courses of fluconazole or other therapies.
- Patients with hypokalemia, or advanced cardiac failure
- Patients with renal insufficiency
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IL-23 Therapy with Placebo IL-23 Therapy Placebo will be blindly administered as capsules for oral consumption. On the first day, 200 mg will be given. Subjects will then take 100 mg once daily for thirteen days. IL-23 Therapy with Fluconazole IL-23 Therapy Fluconazole will be blindly administered as capsules for oral consumption. On the first day, 200 mg will be given. Subjects will then take 100 mg once daily for thirteen days. IL-23 Therapy with Placebo Placebo Placebo will be blindly administered as capsules for oral consumption. On the first day, 200 mg will be given. Subjects will then take 100 mg once daily for thirteen days. IL-23 Therapy with Fluconazole Fluconazole Fluconazole will be blindly administered as capsules for oral consumption. On the first day, 200 mg will be given. Subjects will then take 100 mg once daily for thirteen days.
- Primary Outcome Measures
Name Time Method Proportion of subjects achieving clinical response Week 12 post-Fluconazole Initiation Participants with clinical response are those participants with a reduction of the Crohn's Disease Activity Index (CDAI) by 100 or more points from baseline at week 12 post-Fluconazole initiation.
- Secondary Outcome Measures
Name Time Method Proportion of subjects achieving clinical remission Week 12 post-Fluconazole Initiation Participants achieving clinical remission are those participants with a Crohn's Disease Activity Index (CDAI) score of no greater than 150 points at week 12 post-Fluconazole initiation.
Proportion of patients achieving endoscopic response or remission Up to 1 Year post-Fluconazole Initiation Participants achieving endoscopic response are those participants with a reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD) of at least 50% from baseline. Participants achieving endoscopic remission are those participants with an SES-CD score less than or equal to 2
Trial Locations
- Locations (1)
Weill Cornell Medicine
🇺🇸New York, New York, United States