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Trial record 1 of 2 for:    CD-IT
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Evaluation of the Response of Itraconazole and Terbinafine Therapy in Subjects With Crohn's Disease (CD-IT)

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ClinicalTrials.gov Identifier: NCT05049525
Recruitment Status : Recruiting
First Posted : September 20, 2021
Last Update Posted : April 21, 2022
Sponsor:
Information provided by (Responsible Party):
Montreal Heart Institute

Brief Summary:
This study will evaluate the response of itraconazole and terbinafine therapy compared to placebo in patients with mild to moderate Crohn's disease (CD).

Condition or disease Intervention/treatment Phase
Crohn's Disease Inflammatory Bowel Diseases Drug: Itraconazole 400 mg/day and terbinafine 500 mg/day administered orally. Drug: Itraconazole's matching placebo 400 mg/day and terbinafine's matching placebo 500 mg/day administered orally. Phase 2

Detailed Description:
This multicenter, randomized, double-blind, placebocontrolled, phase II, proof of concept study will randomize 68 subjects at 2 to 5 clinical sites in Canada. Following signature of informed consent, subjects who meet entry criteria will be randomized in a 1:1 ratio to receive either itraconazole and terbinafine, or matching placebos. During the first 4 weeks subjects will receive itraconazole 200 mg twice daily or matching placebo, followed by itraconazole 200 mg twice daily and terbinafine 250 mg twice daily or matching placebos for the remaining 16 weeks. The 2 drugs will be administered orally.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of the Response of Itraconazole and Terbinafine Therapy in Subjects With Crohn's Disease Not Responding Adequately to Current Therapy
Actual Study Start Date : February 22, 2022
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024


Arm Intervention/treatment
Active Comparator: Itraconazole and Terbinafine
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.
Drug: Itraconazole 400 mg/day and terbinafine 500 mg/day administered orally.
Itraconazole capsules of 100 mg, antifungal agent. Terbinafine tablets 250 mg (as terbinafine hydrochloride), antifungal agent.

Placebo Comparator: Placebo
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.
Drug: Itraconazole's matching placebo 400 mg/day and terbinafine's matching placebo 500 mg/day administered orally.
Matching placebo of itraconazole capsules of 100 mg, antifungal agent. Matching placebo of terbinafine tablets 250 mg, antifungal agent.




Primary Outcome Measures :
  1. To evaluate the response of itraconazole and terbinafine therapy compared to placebo in subjects with CD, assessed by the Modified Harvey Bradshaw Index (HBI). [ Time Frame: 20 Weeks ]
    Clinical response defined as a decrease from baseline to end of treatment in Modified Harvey Bradshaw HBI score from 0 to greater than 16 (it will depend on the number of soft stools per day). The higher the score the worse the outcome.


Secondary Outcome Measures :
  1. To evaluate the response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on clinical remission assessed by the HBI. [ Time Frame: 20 Weeks ]
    Clinical remission defined as an Modified Harvey Bradshaw Index (HBI) at end of treatment ≤ 4 points.

  2. To evaluate the endoscopic response of the itraconazole and terbinafine therapy compared to placebo in subjects with CD as assessed by the Simplified Endoscopic Score for Crohn's disease (SES-CD). [ Time Frame: 20 Weeks ]
    Endoscopic response defined as the change from baseline to end of treatment in Simplified Endoscopic Score for Crohn's Disease (SES-CD). Score from 0 to 60. The higher the score the worse the outcome.

  3. To evaluate the response to treatment of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on FC levels. [ Time Frame: 20 Weeks ]
    Change from baseline to end of treatment in faecal calprotectin (FC) levels

  4. To evaluate the response to treatment of the itraconazole and terbinafine therapy compared to placebo in subjects with CD assessed by the HBI. [ Time Frame: 20 Weeks ]
    Change from baseline to end of treatment in HBI.

  5. To evaluate the response to treatment of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on inflammatory markers. [ Time Frame: 20 Weeks ]
    Change from baseline to end of treatment in C-reactive protein (CRP) levels.

  6. To evaluate the response to treatment of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on serology markers. [ Time Frame: 20 Weeks ]
    Change from baseline to end of treatment in Anti-Saccharomyces cerevisiae antibodies (ASCA) levels.

  7. To evaluate the response to treatment of the itraconazole and terbinafine therapy compared to placebo in subjects with CD on serology markers. [ Time Frame: 28 Weeks ]
    Change from baseline to 8 weeks post end of treatment in ASCA levels.

  8. To evaluate the response of itraconazole and terbinafine therapy compared to placebo in subjects with CD, assessed by the Modified Harvey Bradshaw Index (HBI), for the subgroup of patients with positive ASCA. [ Time Frame: 20 Weeks ]
    Clinical response defined as a decrease from baseline to end of treatment in Modified Harvey Bradshaw HBI score from 0 to greater than 16 (it will depend on the number of soft stools per day). The higher the score the worse the outcome. This outcome will be evaluated in the subgroup of patients with positive ASCA (as measured on frozen plasma samples at end of the study).


Other Outcome Measures:
  1. 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. [ Time Frame: 28 Weeks ]
    To determine the link between genetics and the response to therapy and inflammation. The microbiote genes will also be evaluated.

  2. To evaluate steroid use between active and placebo groups at study completion. [ Time Frame: 28 Weeks ]
    Steroid Use in Subjects with Crohn's Disease will be reported as the proportion of subjects who's steroid use was decreased. increased, changed or stopped.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with endoscopy/radiology confirmation of active disease within 6 months prior to enrolment;
  • Mild to moderate active CD defined by the HBI score of ≥ 5 to ≤ 16 at baseline;
  • Elevated FC levels at baseline (≥ 250 mcg/gm);
  • Female of childbearing potential must have a negative urine pregnancy test at screening and at randomization baseline Visit 2. Women are considered not of childbearing potential if they either:
  • Have had a hysterectomy or tubal ligation prior to baseline visit or;
  • Are postmenopausal defined as no menses for 12 months or a FSH level (if available) in the menopausal range.
  • Women of childbearing potential must agree to use an effective double method of birth control throughout the study: barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, and diaphragm) in combination with other methods of contraception including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, abstinence, or a sterile sexual partner.
  • Subjects with the capacity to provide informed consent.

Exclusion Criteria:

  • Subject with a current diagnosis of ulcerative colitis (UC);
  • Contraindication to the use of itraconazole including congestive heart failure, ventricular dysfunction, ventricular arrhythmia, or negative inotropic state;
  • Subjects with elevated or abnormal liver enzymes (ALT/AST>3 ULN) or patients with pre-existing chronic or active liver disease at screening;
  • Female subject who is pregnant, planning to become pregnant during the study, or breastfeeding;
  • Subject with renal impairment (creatinine clearance ≤ 50 mL/min using Cockcroft-Gault equation);
  • Subject with a known hypersensitivity to itraconazole, terbinafine, or any of their excipients;
  • Subjects on medications which interact with itraconazole: methadone, pimozide, quinidine or other CYP3A4 inhibitors;
  • Positive C. difficile toxin test at screening;
  • Use of steroid greater than 20 mg/day;
  • Change of steroid dosage in the 2 weeks prior to enrolment;
  • Change in CD therapy:

    • The Anti-TNFs, anti-integrins, anti-IL12/23 in the 4 months prior to enrolment;
    • Thiopurines or methotrexate (MTX), in the 2 months prior to enrolment;
  • Participation in other clinical trial within 30 days of signing the Information and Consent Form (ICF).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05049525


Contacts
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Contact: Jean-Claude Tardif, MD 514-376-3330 ext 3612 jean-claude.tardif@icm-mhi.org
Contact: Marianne Rufiange 514-461-1300 ext 2036 marianne.rufiange@mhicc.org

Locations
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Canada, Quebec
CIUSSS de l'Est-de-l'Île-de-Montréal, Hôpital Maisonneuve-Rosemont Recruiting
Montréal, Quebec, Canada, H1T2M4
Contact: Louis-Charles Rioux, MD         
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) Recruiting
Montréal, Quebec, Canada, H2X0A9
Contact: Edmond-Jean Bernard, MD         
McGill University Health Center Recruiting
Montréal, Quebec, Canada, H3G1A4
Contact: Talat Bessissow, MD         
Sponsors and Collaborators
Montreal Heart Institute
Investigators
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Principal Investigator: Jean-Claude Tardif, MD Montreal Heart Institute (MHI)
Principal Investigator: Edmond-Jean Bernard, MD Centre hospitalier de l'Université de Montréal (CHUM)
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Responsible Party: Montreal Heart Institute
ClinicalTrials.gov Identifier: NCT05049525    
Other Study ID Numbers: MHICC-2019-001
First Posted: September 20, 2021    Key Record Dates
Last Update Posted: April 21, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Montreal Heart Institute:
Endoscopy
Radiology
Itraconazole
Terbinafine
Chronic Inflammatory Disorder
Malassezia Restricta
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Itraconazole
Hydroxyitraconazole
Terbinafine
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors