Clinical trial NCT06981520: Caspase-1 Activity, IL-1beta, and IL-18 in Patients With FMF
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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Familial Mediterranean Fever
Intestinal Disease
Genetic Disease
Fever
Lead sponsor: Hitit University
Sponsor class: OTHER
First posted: 2025-05-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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). 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.

Eligibility criteria: Inclusion Criteria:Age 18 years or older

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)

Severe infection, active malignancy, or other systemic disease affecting intestinal mucosa

Inadequate biopsy specimen quality for histopathological evaluation

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Primary outcomes:
measure: Level of IL-1 in Mucosal Biopsies (Semi-Quantitative Score)
timeFrame: Single time point, Day 1 (during biopsy analysis)
measure: Level of IL-18 in Mucosal Biopsies (Semi-Quantitative Score)
timeFrame: Single time point, Day 1 (during biopsy analysis)
measure: Caspase-1 Expression in Mucosal Biopsies (Semi-Quantitative Score)
timeFrame: Single time point, Day 1 (during biopsy analysis)
Secondary outcomes:
Other outcomes:
Locations:
city: Çorum
country: Turkey
facility: Hitit University Erol Olçok Training and Research Hospital
Study officials:
affiliation: Hitit University Faculty of Medicine, Turkey
name: Mustafa Şahin, Assoc.Prof
role: PRINCIPAL_INVESTIGATOR
References: