Effect of Fluconazole on the Levels of ASCA After Surgical Resection for Crohn's Disease. (AscaMC)

Effect of Fluconazole on the Levels of Anti-Saccharomyces Cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn's Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo

This was prospective study randomized in two controlled parallel groups verum versus placebo. The objectives were to assess the influence of antifungal treatment with Fluconazole (FCZ) on the rate of ASCA and endoscopic recurrence at 6 months. The rational was based on our previous research having established i) a link between intestinal inflammation and the opportunistic fungal pathogen C. albicans -a yeast colonizing the human digestive tract- ii) the demonstration that this yeast species could be at the origin of ASCA, a prominent serological marker of CD. It was therefore hypothesized that the FCZ could lower the rate of ASCA and/or reduce the occurrence of recurrences.

Study Overview

• Status: Terminated
• Conditions: Crohn's Disease Aggravated
• Intervention / Treatment: Other: Placebo; Drug: Fluconazole

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France
    • CHRU, Hôpital Claude HURIEZ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Crohn disease patients with a small intestine localisation (ileum or ileocecal)
2. Ileal or ileocecal resection in the month before inclusion (resection of all macroscopic lesions). If resection with temporary stoma, the patient may be included at the time of surgery to restore the continuity

3. Patient with low risk of recurrence according to the following criteria:

   (i) Total length of the resection(s) of the small intestine less than 100 cm (ii) Segmental colectomy leaving in place at least another colonic segment as the rectum

4. Preoperative rate of ASCA> 70 arbitrary units (+/- 10%)
5. Informed consent signed to be involved in the study

Exclusion Criteria:

1. Pregnant women or without adequate contraception
2. Total length of the resection(s) of the small intestine more than 1 meter
3. Subtotal colic resection
4. Preoperative rate of ASCA<63 arbitrary units (+/- 10%)
5. Known hypersensitivity to fluconazole or other azoles
6. Known liver disease or transaminase levels >1.5 the normal rate
7. Patient with renal failure
8. Inability to read and sign the informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluconazole; 200mg per day for 6 months	Drug: Fluconazole; 200 mg/ day
Placebo Comparator: Placebo; One capsule per day for 6 months	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of ASCA	the dosage of ASCA in the serum	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of yeast digestive colonization		during 6 months
Quantification of yeast digestive colonization		during 6 months
Endoscopic recurrence : Rutgeerts Score>1		6 months
Clinical recurrence : surgery for CD (except for proctological surgery)		6 months
Appearance or not of a clinical recurrence assessed by Crohn Disease Activity Index (CDAI >=220)		6 months
Number of patients with adverse events as a measure of safety	Evaluate the clinical and biological safety of the daily dose of fluconazole in this population	during 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Pierre Desreumaux, MD, PhD, University Hospital, Lille

Publications and helpful links

General Publications

• Sendid B, Salvetat N, Sarter H, Loridant S, Cunisse C, Francois N, Aijjou R, Gele P, Leroy J, Deplanque D, Jawhara S, Weissmann D, Desreumaux P, Gower-Rousseau C, Colombel JF, Poulain D. A Pilot Clinical Study on Post-Operative Recurrence Provides Biological Clues for a Role of Candida Yeasts and Fluconazole in Crohn's Disease. J Fungi (Basel). 2021 Apr 22;7(5):324. doi: 10.3390/jof7050324.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimate): December 19, 2016

Study Record Updates

• Last Update Posted (Estimate): December 19, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Crohn disease; Candida; ASCA
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: 2006_27; 2008-000717-30 (EudraCT Number); PHRC2006R/1903 (Other Identifier: PHRC number, DGOS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No