Study of Colchicine Resistance in Familial Mediterranean Fever

NCT05418686 | Completed

• 1 other identifier: APHP211442
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Five to 10% of familial mediterranean patients are considered colchicine-resistant (i.e. patients with a persistent inflammatory syndrome, despite taking the maximum tolerated dose of colchicine daily). The recommended treatment in this case is a subcutaneous anti-interleukin 1 biotherapy (anakinra or canakinumab). These treatments are expensive (1,000 to 12,000 euros/month). However, for a patient to be considered colchicine-resistant, compliance with the treatment must be verified. Furthermore specific activation of the pyrin inflammasome by Clostrioides difficile toxin and the overrepresentation of these bacteria in the stools of our patients led us to systematically search for them in our resistant patients. The demonstration of the involvement of C. difficile in the imbalance of the disease has not yet been published. The colchiresist study aim to better characterize colchicine-resistance by confirming good compliance to treatment with colchicine hair measurement and by looking for clostrioides infection or intestinal dysbiosis.

Conditions

Mediterranean Fever; Colchicine Resistance

Keywords

Familial mediterranean fever; Colchicin-resistant; Drug compliance; Microbiota; Drug resistance; clostrioides difficile; interleukin-1; second-line therapy.

Outcome Measures

Primary Outcomes (1)

• Amount of colchicine measured in the first 2 cm of hair from the scalp of an FMF patient considered colchicine resistant or from pubic hair in patients with bald or colored hair, which corresponds to the average compliance of the last 2 months of intake

  To assess 2-month compliance with colchicine in patients with FMF considered resistant via capillary drug dosage

  Through study completion, an average of 18 months

Secondary Outcomes (6)

• Correlation between the amount of colchicine measured in the hair and the blood and urine levels of colchicine attesting to the last days' intake.

  Through study completion, an average of 18 months

• Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD

  Through study completion, an average of 18 months

• Composition of the fecal microbiota (search for an overrepresentation of clostridiae) in colchicine-resistant patients patients with colchicine resistance

  Through study completion, an average of 18 months

• Testing for clostridioides difficile toxin B in colchicin-resistant patients

  Through study completion, an average of 18 months

• Dosage of proinflammatory cytokines IL1, IL6, IL18, TNFa and il1Ra.

  Through study completion, an average of 18 months

Study Arms (1)

Colchicine-resistant Familial Mediterranean Fever patients

EXPERIMENTAL

Biological: Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients.

Interventions

Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients. BIOLOGICAL

* Adherence to colchicine therapy will be assessed by the Girerd questionnaire (6 questions ) completed by the patient at the inclusion visit. * A blood sample (8ml) is taken, including a haemogram, CRP and creatinine and proteinuria. * Standard on-site stool analysis for C. difficile toxin. For research purposes, samples of: * Stool. If the patient is unable to produce stools on the day of the visit, a collection kit with 2 tubes containing a preservative will be given to him/her as well as a stamped envelope to take the sample at home and send it by post within 10 days according to a validated procedure. * A strand of hair with the diameter of a pencil and a minimum length of 2 cm, in the region of the posterior vertex. * In patients with baldness or bleached hair only: pubic and/or axillary hair, a pencil-sized strand. * Additional blood (5ml) and urine (2ml) samples for colchicine determination.

Colchicine-resistant Familial Mediterranean Fever patients

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients considered colchicine-resistant according to EULAR criteria reviewed by an expert consensus:
• Persistence of signs of activity (at least one attack per month for at least 3 months) despite taking the maximum tolerated dosage of colchicine.
• Signature of an informed consent by the patient (or his parents if under 18 years of age)
• Patients affiliated to a social security system

You may not qualify if:

• \- Patients participating in another interventional trial

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine

Paris, 75020, France

Location

MeSH Terms

Conditions

Brucellosis; Familial Mediterranean Fever; Medication Adherence

Condition Hierarchy (Ancestors)

Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Léa SAVEY, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 14, 2022
• Study Start: December 9, 2022
• Primary Completion: July 4, 2023
• Study Completion: October 27, 2023
• Last Updated: April 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)