Clinical trial NCT05418686: Study of Colchicine Resistance in Familial Mediterranean Fever
Official title: Study Of Colchicine Resistance In Familial Mediterranean Fever
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mediterranean Fever
Colchicine Resistance
Keywords: Familial mediterranean fever
Colchicin-resistant
Drug compliance
Microbiota
Drug resistance
clostrioides difficile
interleukin-1
second-line therapy.
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-06-14
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Detailed description: Patients meeting the criteria for colchicine resistance will be included in a follow-up visit.

* Adherence to colchicine therapy will be assessed by the Girerd questionnaire completed by the patient at the inclusion visit.
* A blood test is performed including a haemogram, CRP and SAA, creatinine and proteinuria.
* a standard stool analysis on site to look for C. difficile toxin.

For research purposes, samples of:

* Stool.
* A strand of hair with the diameter of a pencil and a minimum length of 2 cm, in the region of the posterior vertex, where the growth and integration are relatively constant to avoid variability.
* In patients with baldness or bleached hair only: pubic and/or axillary hair will be taken, The samples will then be processed without segmentation.
* Additional blood (5ml) and urine (2ml) samples for colchicine dosage. The patient's participation ends after this visit

Eligibility criteria: Inclusion Criteria:

Inclusion Criteria Age ≥ 12 years with no upper age limit -Patients with familial Mediterranean fever (FMF) meeting international criteria for the disease (Livneh criteria) and carrying 2 pathogenic mutations in the MEFV gene.

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.
* Persistence of a biological inflammatory syndrome after exclusion of other causes and despite taking a 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

Exclusion Criteria:

- Patients participating in another interventional trial

Primary outcomes:
measure: 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
timeFrame: Through study completion, an average of 18 months
Secondary outcomes:
measure: Correlation between the amount of colchicine measured in the hair and the blood and urine levels of colchicine attesting to the last days' intake.
timeFrame: Through study completion, an average of 18 months
measure: Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD
timeFrame: Through study completion, an average of 18 months
measure: Composition of the fecal microbiota (search for an overrepresentation of clostridiae) in colchicine-resistant patients patients with colchicine resistance
timeFrame: Through study completion, an average of 18 months
measure: Testing for clostridioides difficile toxin B in colchicin-resistant patients
timeFrame: Through study completion, an average of 18 months
measure: Dosage of proinflammatory cytokines IL1, IL6, IL18, TNFa and il1Ra.
timeFrame: Through study completion, an average of 18 months
measure: Percentage of patients for whom a prescription of anti-IL-1 biotherapy could have been avoided (i.e. poor compliance with Colchicine and/or Clostrioides Difficile infection)
timeFrame: Through study completion, an average of 18 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Léa SAVEY, MD
role: PRINCIPAL_INVESTIGATOR
References: