What side effects are associated with this type of intervention?

Common treatments for Crohn's Disease include glucocorticoids, thiopurines, biologic agents (such as anti-TNF agents), and antibiotics. Glucocorticoids can cause side effects like weight gain, osteoporosis, and increased infection risk. Thiopurines may lead to bone marrow suppression and liver toxicity. Biologic agents, including anti-TNF agents, can result in infections, infusion reactions, and potential malignancy risks. Antibiotics like metronidazole and ciprofloxacin may cause gastrointestinal upset and, in rare cases, tendonitis or neuropathy. While Itraconazole and Terbinafine are not standard treatments for Crohn's Disease, they can cause liver toxicity and gastrointestinal disturbances.

What prior FDA approvals exist?

FDA-approved treatments for Crohn's Disease primarily include biologic agents and immunomodulators. Biologic agents such as infliximab, adalimumab, and certolizumab pegol target tumor necrosis factor-alpha (TNF-alpha) to reduce inflammation. Other biologics like vedolizumab and ustekinumab target integrins and interleukins, respectively. Immunomodulators such as azathioprine and methotrexate are also used. There are no FDA-approved treatments for Crohn's Disease that specifically inhibit ergosterol synthesis or squalene epoxidase, as itraconazole and terbinafine do for fungal infections.

What other types of research exist?

Promising novel alternatives for Crohn's Disease treatment in 2024 include anti-TNF agents like infliximab, which are particularly valuable for refractory cases, and exclusive enteral nutrition (EEN) for mucosal healing and inflammation suppression. Additionally, emerging biologics and small molecules targeting different inflammatory pathways may offer new therapeutic options.

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Anti-fungal

Itraconazole + Terbinafine for Crohn's Disease (CD-IT Trial)

Phase 2

Waitlist Available

Led By Edmond-Jean Bernard, MD

Research Sponsored by Montreal Heart Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subjects with the capacity to provide informed consent

Be older than 18 years old

Must not have

Subjects on medications which interact with itraconazole: methadone, pimozide, quinidine or other CYP3A4 inhibitors

Female subject who is pregnant, planning to become pregnant during the study, or breastfeeding

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 weeks

Summary

This trial will test if two antifungal medications, itraconazole and terbinafine, can help people with mild to moderate Crohn's disease. The study will compare these drugs to see if they reduce inflammation in the gut. Researchers hope these medications can offer a new way to manage Crohn's disease symptoms. Terbinafine and itraconazole are antifungal medications that have been used to treat various fungal infections, with terbinafine showing superior efficacy in some cases.

Who is the study for?

This trial is for adults with mild to moderate Crohn's Disease confirmed by endoscopy or radiology within the last 6 months. Women who can have children must test negative for pregnancy and use double contraception. Participants need a certain disease severity score, cannot be pregnant, breastfeeding, or planning pregnancy during the study, and should not have severe liver or kidney issues or be on conflicting medications.

What is being tested?

The trial tests itraconazole (400 mg/day) and terbinafine (500 mg/day), both antifungal medications, against placebos to see if they help with Crohn's Disease symptoms. Patients will take these orally every day to compare their effectiveness in treating the condition.

What are the potential side effects?

Itraconazole may cause heart problems like congestive heart failure and arrhythmias; it can also affect liver enzymes leading to potential liver damage. Terbinafine might lead to digestive issues, changes in taste sensation, headaches, dizziness or skin reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I understand and can agree to the study's procedures and risks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not taking methadone, pimozide, quinidine, or drugs that strongly affect drug metabolism.

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I am pregnant, planning to become pregnant, or breastfeeding.

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My liver enzymes are high or I have a liver condition.

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I have been diagnosed with ulcerative colitis.

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My kidney function is reduced with a creatinine clearance ≤ 50 mL/min.

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I take more than 20 mg of steroids daily.

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I cannot take itraconazole due to heart issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To evaluate the response of itraconazole and terbinafine therapy compared to placebo in subjects with CD, assessed by the Modified Harvey Bradshaw Index (HBI).

Secondary study objectives

To evaluate the effect of study treatment on the primary endpoint in the subgroup of patients with positive ASCA (as measured on frozen plasma samples at end of the study).

To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on clinical remission assessed by the HBI.

To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on endoscopic response assessed by the Simplified Endoscopic Score for Crohn's disease (SES-CD).

+1 more

Other study objectives

Exploratory analyses using genetic data (pharmacogenomic and metagenomics) as well as microbiotic testing will be described at a later time point and in a separate document.

To evaluate steroid use between active and placebo groups at study completion.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: Itraconazole and TerbinafineActive Control1 Intervention

During the first 4 weeks itraconazole will be administered alone at 200 mg twice daily, followed by itraconazole 200 mg twice daily and terbinafine 250 mg twice daily for the remaining 16 weeks. Both drugs will be administered orally.

Group II: PlaceboPlacebo Group1 Intervention

During the first 4 weeks a placebo will be administered alone at 200 mg twice daily, followed by placebo 200 mg twice daily and another placebo 250 mg twice daily for the remaining 16 weeks. Both placebos will be administered orally.

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Crohn's Disease include anti-inflammatory drugs like corticosteroids, which reduce inflammation by suppressing the immune response, and 5-ASA agents, which target the lining of the gut to reduce inflammation. Immunosuppressants such as azathioprine and methotrexate inhibit the immune system to prevent it from attacking the gastrointestinal tract. Biologics like anti-TNF agents (e.g., infliximab) target specific proteins involved in the inflammatory process. Antibiotics may also be used to treat infections or complications. These treatments are crucial for managing symptoms, inducing remission, and preventing complications. Itraconazole and Terbinafine, which inhibit ergosterol synthesis and squalene epoxidase respectively, are being studied for their potential to alter the gut microbiome and immune response, offering a novel approach to managing Crohn's Disease.