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Study of Colchicine Resistance in Familial Mediterranean Fever (COLCHI-RESIST)

Primary Purpose

Mediterranean Fever, Colchicine Resistance

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients.
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Mediterranean Fever focused on measuring Familial mediterranean fever, Colchicin-resistant, Drug compliance, Microbiota, Drug resistance, clostrioides difficile, interleukin-1, second-line therapy.

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Colchicine-resistant Familial Mediterranean Fever patients

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Correlation between the amount of colchicine measured in the hair and the blood and urine levels of colchicine attesting to the last days' intake.
To study blood and urine colchicine dosage in FMF patients considered resistant to colchicine
Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD
Compare hair dosing to self-reported compliance
Composition of the fecal microbiota (search for an overrepresentation of clostridiae) in colchicine-resistant patients patients with colchicine resistance
Studying the composition of the fecal microbiota in colchicine-resistant FMF patients
Testing for clostridioides difficile toxin B in colchicin-resistant patients
Testing colchicine-resistant FMF patients for clostridioides difficile toxin to rule out chronic asymptomatic carriage
Dosage of proinflammatory cytokines IL1, IL6, IL18, TNFa and il1Ra.
Study blood levels of proinflammatory cytokines in colchicine-resistant patients, in particular IL1 and il1RA
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)
Determine the percentage of patients labeled colchicine resistant who were actually noncompliant or chronically infected with pyrin-activating bacteria like clostridioides difficile

Full Information

First Posted
June 10, 2022
Last Updated
June 10, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT05418686
Brief Title
Study of Colchicine Resistance in Familial Mediterranean Fever
Acronym
COLCHI-RESIST
Official Title
Study Of Colchicine Resistance In Familial Mediterranean Fever
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 2022 (Anticipated)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mediterranean Fever, Colchicine Resistance
Keywords
Familial mediterranean fever, Colchicin-resistant, Drug compliance, Microbiota, Drug resistance, clostrioides difficile, interleukin-1, second-line therapy.

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Colchicine-resistant Familial Mediterranean Fever patients
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients.
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
To assess 2-month compliance with colchicine in patients with FMF considered resistant via capillary drug dosage
Time Frame
Through study completion, an average of 18 months
Secondary Outcome Measure Information:
Title
Correlation between the amount of colchicine measured in the hair and the blood and urine levels of colchicine attesting to the last days' intake.
Description
To study blood and urine colchicine dosage in FMF patients considered resistant to colchicine
Time Frame
Through study completion, an average of 18 months
Title
Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD
Description
Compare hair dosing to self-reported compliance
Time Frame
Through study completion, an average of 18 months
Title
Composition of the fecal microbiota (search for an overrepresentation of clostridiae) in colchicine-resistant patients patients with colchicine resistance
Description
Studying the composition of the fecal microbiota in colchicine-resistant FMF patients
Time Frame
Through study completion, an average of 18 months
Title
Testing for clostridioides difficile toxin B in colchicin-resistant patients
Description
Testing colchicine-resistant FMF patients for clostridioides difficile toxin to rule out chronic asymptomatic carriage
Time Frame
Through study completion, an average of 18 months
Title
Dosage of proinflammatory cytokines IL1, IL6, IL18, TNFa and il1Ra.
Description
Study blood levels of proinflammatory cytokines in colchicine-resistant patients, in particular IL1 and il1RA
Time Frame
Through study completion, an average of 18 months
Title
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)
Description
Determine the percentage of patients labeled colchicine resistant who were actually noncompliant or chronically infected with pyrin-activating bacteria like clostridioides difficile
Time Frame
Through study completion, an average of 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Léa SAVEY, MD
Phone
0033156017431
Email
lea.savey@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie Georgin-Lavialle, PD, PhD
Phone
0033156017431
Email
sophie.georgin-lavialle@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Léa SAVEY, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Léa SAVEY, MD
Phone
0033156016791
Email
lea.savey@aphp.fr
First Name & Middle Initial & Last Name & Degree
Sophie Georgin-Lavialle, MD, PhD
Phone
0033156017431
Email
sophie.georgin-lavialle@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of Colchicine Resistance in Familial Mediterranean Fever

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