Mediterranean FeverCOLCHI-RESISTNCT05418686
Study of Colchicine Resistance in Familial Mediterranean Fever
A study testing Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients. in people with Mediterranean Fever and Colchicine Resistance, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Mediterranean Fever, Colchicine Resistance
- What is being tested?
- Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 9 Dec 2022to 27 Oct 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Patients participating in another interventional trial
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Médecine Interne. Hôpital Tenon, 4 Rue de la Chine
Paris, 75020
About this study
Official title: 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.
Read the 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
- Conditions
- Mediterranean Fever, Colchicine Resistance
- Being tested
- Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients.
- Keywords
- Familial mediterranean fever, Colchicin-resistant, Drug compliance, Microbiota, Drug resistance, clostrioides difficile, interleukin-1, second-line therapy.
- Medical subject headings
- Brucellosis, Familial Mediterranean Fever, Medication Adherence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Colchicine-resistant Familial Mediterranean Fever patients | Experimental | Not described Receives: Biological: Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
To study blood and urine colchicine dosage in FMF patients considered resistant to colchicine
Measured: Through study completion, an average of 18 months
Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD
Compare hair dosing to self-reported compliance
Measured: 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
Studying the composition of the fecal microbiota in colchicine-resistant FMF patients
Measured: Through study completion, an average of 18 months
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
Measured: Through study completion, an average of 18 months
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
Measured: Through study completion, an average of 18 months
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
Measured: Through study completion, an average of 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2022
- Study start9 Dec 2022
- Primary completion4 Jul 2023
- Study completion27 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mediterranean FeverStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Léa SAVEY, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05418686
- Sponsor's protocol ID
- APHP211442
- Acronym
- COLCHI-RESIST
- Status last verified
- Apr 2024
- First submitted
- 10 Jun 2022
- Last updated
- 8 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study Of Colchicine Resistance In Familial Mediterranean Fever
- ClinicalTrials.gov ID
- NCT05418686
- Acronym / sponsor ID
- COLCHI-RESIST / APHP211442
- Conditions
- Mediterranean Fever, Colchicine Resistance
- Keywords
- Familial mediterranean fever, Colchicin-resistant, Drug compliance, Microbiota, Drug resistance, clostrioides difficile, interleukin-1, second-line therapy.
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 9 Dec 2022 (actual)
- Primary completion
- 4 Jul 2023 (actual)
- Study completion
- 27 Oct 2023 (actual)
- First posted
- 14 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Colchicine-resistant Familial Mediterranean Fever patients | Experimental | Biological: Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (1 listed)
- Patients participating in another interventional trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients.* 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. | Biological | Colchicine-resistant Familial Mediterranean Fever patients |
Primary outcome
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
6 secondary outcomes
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
Correlation between capillary colchicine dosage and colchicine compliance assessed with the 6-item GIRERD
Time frame: 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
Time frame: Through study completion, an average of 18 months
Testing for clostridioides difficile toxin B in colchicin-resistant patients
Time frame: Through study completion, an average of 18 months
Dosage of proinflammatory cytokines IL1, IL6, IL18, TNFa and il1Ra.
Time frame: Through study completion, an average of 18 months
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Léa SAVEY, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Capillary colchicine dosage in colchicine-resistant Familial Mediterranean Fever patients. in people with Mediterranean Fever and Colchicine Resistance, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Through study completion, an average of 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2024.