Familial Mediterranean FeverFMFNCT06981520
Caspase-1 Activity, IL-1beta, and IL-18 in Patients With FMF
An observational study of Familial Mediterranean Fever and Intestinal Disease, run by Hitit University at 1 site in Turkey (Türkiye).
Trial summary
This study aims to investigate the intestinal mucosal expression of key inflammatory markers, namely Interleukin-1 (IL-1), Interleukin-18 (IL-18), and Caspase-1, in patients with Familial Mediterranean Fever (FMF). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Familial Mediterranean Fever, Intestinal Disease, Genetic Disease
- How many people
- 30 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 10 Jul 2025to 11 May 2026
- How long will I take part?
- 8 Months
- Phase
- Observational
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: This study includes adult patients diagnosed with Familial Mediterranean Fever (FMF) who underwent routine endoscopic evaluation with intestinal mucosal biopsies. A control group composed of age- and sex-matched individuals without inflammatory or autoimmune diseases was also included for comparative analysis. All participants were retrospectively selected based on availability of adequate tissue samples and relevant clinical data.
Who may be able to join
- Confirmed diagnosis of Familial Mediterranean Fever (FMF) according to Tel-Hashomer clinical criteria and/or MEFV gene mutation analysis (for FMF group)
- Undergoing routine endoscopy with mucosal biopsy sampling
- Availability of sufficient formalin-fixed paraffin-embedded (FFPE) tissue for immunohistochemical analysis
- For controls: absence of systemic inflammatory or autoimmune disease -
- Exclusion Criteria:History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- Current use of immunosuppressive therapy (excluding colchicine)
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- Severe infection, active malignancy, or other systemic disease affecting intestinal mucosa
- Inadequate biopsy specimen quality for histopathological evaluation
- -
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Hitit University Erol Olçok Training and Research Hospital
Çorum, 19040
About this study
Official title: Effect of Caspase-1 Activity, IL-1beta, and IL-18 on Inflammation in the Mucosa of the Small Intestine of Patients With FMF
This study aims to investigate the intestinal mucosal expression of key inflammatory markers, namely Interleukin-1 (IL-1), Interleukin-18 (IL-18), and Caspase-1, in patients with Familial Mediterranean Fever (FMF). FMF is an autoinflammatory disorder characterized by recurrent episodes of fever and serosal inflammation. Recent studies suggest a possible role of intestinal immune activation in the disease pathogenesis, particularly through inflammasome-related cytokines. To better understand mucosal involvement in FMF, immunohistochemical staining for IL-1, IL-18, and Caspase-1 will be performed on intestinal biopsy samples obtained during routine endoscopic procedures. The staining intensity and distribution patterns will be evaluated and compared with age- and sex-matched healthy controls. The findings may help clarify mucosal inflammatory pathways involved in FMF and provide insight into novel therapeutic targets.
Read the detailed description
Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever, serositis, and elevated acute-phase reactants. The underlying pathophysiology involves mutations in the MEFV gene, which encodes pyrin, a protein involved in the regulation of the inflammasome complex. Aberrant inflammasome activation has been associated with increased production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), mediated through caspase-1 cleavage.
Although FMF primarily affects serosal surfaces, emerging evidence suggests that intestinal mucosal inflammation may also play a role in disease pathogenesis, possibly contributing to atypical symptoms such as abdominal pain, diarrhea, or subclinical intestinal involvement. However, the extent and nature of this mucosal immune activation remain largely unexplored.
This study is designed to evaluate the expression of IL-1, IL-18, and Caspase-1 in intestinal mucosal biopsy specimens obtained from FMF patients during routine endoscopic evaluation. Immunohistochemical staining techniques will be applied to assess the localization and intensity of these markers. The results will be compared to a control group of age- and sex-matched individuals undergoing endoscopy for non-inflammatory indications (e.g., functional gastrointestinal disorders) and without histopathologic mucosal abnormalities.
Staining will be semi-quantitatively scored by two independent pathologists blinded to clinical data. Correlations between cytokine expression levels and clinical characteristics of FMF (e.g., disease duration, mutation status, attack frequency, colchicine response) will also be explored.
This study aims to provide insights into the role of mucosal inflammasome activity in FMF, potentially identifying novel biomarkers or therapeutic targets. By characterizing intestinal expression of key inflammasome-related cytokines, we hope to expand current understanding of FMF pathophysiology beyond classical serosal involvement.
- Medical subject headings
- Familial Mediterranean Fever, Intestinal Diseases, Genetic Diseases, Inborn, Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Grup 1: Group Title: FMF Patients Group/Cohort Label: FMF | 1. FMF Patients (Group/Cohort Description) Patients diagnosed with Familial Mediterranean Fever (FMF) according to clinical criteria and/or genetic analysis. Intestinal mucosal biopsy samples were obtained during routine endoscopy, and immunohistochemical staining for IL-1, IL-18, and Caspase-1 was performed. | |
| Grup 2: Group Title: Healthy Controls Group/Cohort Label: Control | 2. Healthy Controls (Group/Cohort Description) Healthy individuals without any known inflammatory or autoimmune disease, undergoing endoscopy for non-inflammatory indications such as functional gastrointestinal symptoms. Mucosal biopsy samples were collected and analyzed immunohistochemically for IL-1, IL-18, and Caspase-1 expression. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of IL-1 in Mucosal Biopsies (Semi-Quantitative Score)
Semi-quantitative scoring of immunohistochemical staining in mucosal biopsies; comparison between FMF and control groups
Measured: Single time point, Day 1 (during biopsy analysis)
Level of IL-18 in Mucosal Biopsies (Semi-Quantitative Score)
Semi-quantitative scoring of immunohistochemical staining in mucosal biopsies; comparison between FMF and control groups
Measured: Single time point, Day 1 (during biopsy analysis)
Caspase-1 Expression in Mucosal Biopsies (Semi-Quantitative Score)
Semi-quantitative scoring of immunohistochemical staining in mucosal biopsies; comparison between FMF and control groups
Measured: Single time point, Day 1 (during biopsy analysis)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2025
- Study start10 Jul 2025
- Primary completion10 Nov 2025
- Study completion11 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial Mediterranean FeverStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 30 participants (actual)
- Target duration
- 8 Months
Sponsor and investigators
- Lead sponsor
- Hitit University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mustafa Sahin, Hitit University
- Investigators
- Mustafa Şahin, Assoc.Prof, Principal investigator, Hitit University Faculty of Medicine, Turkey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06981520
- Sponsor's protocol ID
- Hitit University, Çorum
- Other IDs
- 2025/37
- Acronym
- FMF
- Status last verified
- Sep 2026
- First submitted
- 29 Apr 2025
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared due to the retrospective nature and ethical restrictions.
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Caspase-1 Activity, IL-1beta, and IL-18 on Inflammation in the Mucosa of the Small Intestine of Patients With FMF
- ClinicalTrials.gov ID
- NCT06981520
- Acronym / sponsor ID
- FMF / Hitit University, Çorum
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Hitit UniversityUniversity, hospital or other
- Study start
- 10 Jul 2025 (actual)
- Primary completion
- 10 Nov 2025 (actual)
- Study completion
- 11 May 2026 (actual)
- First posted
- 20 May 2025 (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.
This study aims to investigate the intestinal mucosal expression of key inflammatory markers, namely Interleukin-1 (IL-1), Interleukin-18 (IL-18), and Caspase-1, in patients with Familial Mediterranean Fever (FMF). FMF is an autoinflammatory disorder characterized by recurrent episodes of fever and serosal inflammation. Recent studies suggest a possible role of intestinal immune activation in the disease pathogenesis, particularly through inflammasome-related cytokines. To better understand mucosal involvement in FMF, immunohistochemical staining for IL-1, IL-18, and Caspase-1 will be performed on intestinal biopsy samples obtained during routine endoscopic procedures. The staining intensity and distribution patterns will be evaluated and compared with age- and sex-matched healthy controls. The findings may help clarify mucosal inflammatory pathways involved in FMF and provide insight into novel therapeutic targets.
Detailed description
Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent episodes of fever, serositis, and elevated acute-phase reactants. The underlying pathophysiology involves mutations in the MEFV gene, which encodes pyrin, a protein involved in the regulation of the inflammasome complex. Aberrant inflammasome activation has been associated with increased production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), mediated through caspase-1 cleavage.
Although FMF primarily affects serosal surfaces, emerging evidence suggests that intestinal mucosal inflammation may also play a role in disease pathogenesis, possibly contributing to atypical symptoms such as abdominal pain, diarrhea, or subclinical intestinal involvement. However, the extent and nature of this mucosal immune activation remain largely unexplored.
This study is designed to evaluate the expression of IL-1, IL-18, and Caspase-1 in intestinal mucosal biopsy specimens obtained from FMF patients during routine endoscopic evaluation. Immunohistochemical staining techniques will be applied to assess the localization and intensity of these markers. The results will be compared to a control group of age- and sex-matched individuals undergoing endoscopy for non-inflammatory indications (e.g., functional gastrointestinal disorders) and without histopathologic mucosal abnormalities.
Staining will be semi-quantitatively scored by two independent pathologists blinded to clinical data. Correlations between cytokine expression levels and clinical characteristics of FMF (e.g., disease duration, mutation status, attack frequency, colchicine response) will also be explored.
This study aims to provide insights into the role of mucosal inflammasome activity in FMF, potentially identifying novel biomarkers or therapeutic targets. By characterizing intestinal expression of key inflammasome-related cytokines, we hope to expand current understanding of FMF pathophysiology beyond classical serosal involvement.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Target follow-up
- 8 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Grup 1: Group Title: FMF Patients Group/Cohort Label: FMF | – | –1. FMF Patients (Group/Cohort Description) Patients diagnosed with Familial Mediterranean Fever (FMF) according to clinical criteria and/or genetic analysis. Intestinal mucosal biopsy samples were obtained during routine endoscopy, and immunohistochemical staining for IL-1, IL-18, and Caspase-1 was performed. |
| Grup 2: Group Title: Healthy Controls Group/Cohort Label: Control | – | –2. Healthy Controls (Group/Cohort Description) Healthy individuals without any known inflammatory or autoimmune disease, undergoing endoscopy for non-inflammatory indications such as functional gastrointestinal symptoms. Mucosal biopsy samples were collected and analyzed immunohistochemically for IL-1, IL-18, and Caspase-1 expression. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- This study includes adult patients diagnosed with Familial Mediterranean Fever (FMF) who underwent routine endoscopic evaluation with intestinal mucosal biopsies. A control group composed of age- and sex-matched individuals without inflammatory or autoimmune diseases was also included for comparative analysis. All participants were retrospectively selected based on availability of adequate tissue samples and relevant clinical data.
Key inclusion criteria (9 listed)
- Confirmed diagnosis of Familial Mediterranean Fever (FMF) according to Tel-Hashomer clinical criteria and/or MEFV gene mutation analysis (for FMF group)
- Undergoing routine endoscopy with mucosal biopsy sampling
- Availability of sufficient formalin-fixed paraffin-embedded (FFPE) tissue for immunohistochemical analysis
- For controls: absence of systemic inflammatory or autoimmune disease -
- Exclusion Criteria:History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Level of IL-1 in Mucosal Biopsies (Semi-Quantitative Score)
Time frame: Single time point, Day 1 (during biopsy analysis)
Semi-quantitative scoring of immunohistochemical staining in mucosal biopsies; comparison between FMF and control groups
Level of IL-18 in Mucosal Biopsies (Semi-Quantitative Score)
Time frame: Single time point, Day 1 (during biopsy analysis)
Semi-quantitative scoring of immunohistochemical staining in mucosal biopsies; comparison between FMF and control groups
Caspase-1 Expression in Mucosal Biopsies (Semi-Quantitative Score)
Time frame: Single time point, Day 1 (during biopsy analysis)
Semi-quantitative scoring of immunohistochemical staining in mucosal biopsies; comparison between FMF and control groups
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 15 Sep 2026.
- Individual participant dataSharing planned: No. IPD will not be shared due to the retrospective nature and ethical restrictions.
Related trials for Familial Mediterranean Fever
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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.
Mustafa Şahin, Assoc.Prof principal investigator
Hitit University Faculty of Medicine, Turkey
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Familial Mediterranean Fever and Intestinal Disease, run by Hitit University at 1 site in Turkey (Türkiye).
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 9 inclusion and 0 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 15 Sep 2026. 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 Turkey (Türkiye). 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?
Level of IL-1 in Mucosal Biopsies (Semi-Quantitative Score) (time frame: Single time point, Day 1 (during biopsy analysis)). The study lists 3 primary outcomes in all. 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 15 Sep 2026.