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Completed

NCT Number: NCT05418686

Study of Colchicine Resistance in Familial Mediterranean Fever

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.

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Key information

Conditions

Mediterranean Fever Bacterial Infections Bacterial Infections and Mycoses Behavior Brucellosis Colchicine Resistance Congenital, Hereditary, and Neonatal Diseases and Abnormalities Familial Mediterranean Fever Genetic Diseases, Inborn Gram-Negative Bacterial Infections Health Behavior Hereditary Autoinflammatory Diseases Infections Medication Adherence Patient Acceptance of Health Care Patient Compliance Treatment Adherence and Compliance

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Paris, 75020, France

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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

    Time frame: Through study completion, an average of 18 months

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

Secondary outcomes

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

    Time frame: Through study completion, an average of 18 months

    To study blood and urine colchicine dosage in FMF patients considered resistant to colchicine

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

    Time frame: Through study completion, an average of 18 months

    Compare hair dosing to self-reported compliance

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

    Time frame: Through study completion, an average of 18 months

    Studying the composition of the fecal microbiota in colchicine-resistant FMF patients

  4. Testing for clostridioides difficile toxin B in colchicin-resistant patients

    Time frame: Through study completion, an average of 18 months

    Testing colchicine-resistant FMF patients for clostridioides difficile toxin to rule out chronic asymptomatic carriage

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

    Time frame: Through study completion, an average of 18 months

    Study blood levels of proinflammatory cytokines in colchicine-resistant patients, in particular IL1 and il1RA

  6. 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)

    Time frame: Through study completion, an average of 18 months

    Determine the percentage of patients labeled colchicine resistant who were actually noncompliant or chronically infected with pyrin-activating bacteria like clostridioides difficile

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: COLCHI-RESIST

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Jun 14, 2022
Registry last updated
Apr 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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