Precision Diagnostics of Functional and Organic Intestinal Pathology Based on Cellular and Molecular Profiling

Not Applicable

• Conditions: Irritable Bowel Syndrome; Healthy Volunteers; Inflammatory Bowel Diseases
• Interventions: Diagnostic Test: cell and molecular diagnostics in accordance with functional test results

• Registration Number: NCT05277662
• Lead Sponsor: Moscow State University of Medicine and Dentistry

Brief Summary

Differential diagnosis of functional and organic intestinal pathology is carried out in line with approved clinical guidelines and includes a significant list of interventions. However, considering the possibility of an "overlap" between functional and organic diseases, as well as the non-specificity of a number of assessment parameters, it is advisably to define new diagnostic approaches and reliable cell and molecular markers, that will update and ensure the precision diagnostics of intestinal diseases. The integrative functional, cell and molecular markers will create the basis and possibilities for the personalized selection of patient therapy.

The study is intended to develop the methods of precision diagnostics based on cellular-molecular profiling with an assessment of functional parameters of the intestine in functional and organic intestinal diseases.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-01
• Status Verified: 2022-01
• Study First Submitted: 2022-01-13
• Study First Submitted QC: 2022-03-11
• Last Update Submitted: 2022-03-11
• Study First Posted: 2022-03-14
• Last Update Posted: 2022-03-14
• Primary Completion: 2022-12-31
• Study Completion: 2023-05-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Signed informed consent
• Gender: Male or Female
• Age: 18-70 years old
• Clinically, laboratory and/or endoscopically confirmed diagnosis of functional (Irritable Bowel Syndrome) and organic (Crohn's Disease, Ulcerative Colitis) intestinal disease
• Healthy volunteers

Exclusion Criteria

• Age under 18 or over 70;
• Acute intestinal infections;
• Antibiotic-associated intestinal lesions;
• Tuberculosis of the intestine;
• Systemic vasculitis;
• Oncological diseases;
• Diverticulitis;
• Solitary rectal ulcer;
• Ischemic colitis;
• Syndrome of bacterial overgrowth;
• Decompensation of chronic diseases of the cardiovascular system or acute cardiovascular diseases;
• Acute or exacerbation of chronic respiratory diseases, respiratory failure;
• Acute infectious diseases;
• Diabetes mellitus;
• Disorders of the blood coagulation system;
• Mental disorders
• Female patients who are pregnant, planning to become pregnant or lactating
• Participation in a clinical trial in the past 3 months and in any other incomplete clinical trials (including follow up - the period of observation after completion of the study)
• Any condition which, in the opinion of investigator, makes the patient unsuitable for participation in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Precision diagnostics profiling	cell and molecular diagnostics in accordance with functional test results	The study will involve subjects with endoscopically, laboratory and clinically confirmed diagnoses of organic and functional intestinal pathology or none of the above (healthy volunteers). All diagnoses are defined in accordance with the validated criteria presented in the clinical guidelines for the diagnosis and treatment of functional bowel pathology (Irritable Bowel Syndrome), 2020, Crohn's Disease (approved by the Ministry of Health of the Russian Federation, 2020), Ulcerative Colitis (approved by the Ministry of Health of the Russian Federation, 2020), in accordance with international criteria of ECCO-ESGAR Guidelines, 2018, 2019. After the initial screening and inclusion in the study, intestinal biopsy samples are taken in accordance with the applied endoscopic examination technique during the endoscopic examination. These biopsy samples will be further used for molecular and immunological diagnostics.

Primary Outcome Measures

Name	Time	Method
Changes of metabolic profile in patients with functional and organic intestinal diseases	2 years	Assessment of metabolome ( gas chromatographic analysis with vapor-phase extraction). Metabolic parameters (Tetradecanoic acid, Hydracinnamic acid, Hexadecanoic acid, Hexanoic acid, Indole, Pentanoic acid) will be measured in feces by gas chromatographic analysis with vapor-phase extraction method. Metabolite extraction methods are performed according to the standard metabolite isolation protocol.The above mentioned metabolites will be measured in intensity of the ion current of the analyzed metabolite, normalized to the total ion current according to the standardized methods.
Changes in immunological profile (systemic) in patients with functional and organic intestinal diseases	2 years	Assessment of systemic cytokine profile by Human Cytokine Screening panel Bio-plex Pro (27 cytokines, concentrations measured in pg/ml). Systemic cytokine profile will be assessed by serum analysis. All cytokine concentrations will be measured in pg/ml.
Changes in genetic profile in patients with functional and organic intestinal diseases	2 years	Assessment of genetic profiling (risk polymorphism assessment). Assessment of risk polymorphisms: NOD2 (rs2066844, rs2066845, rs17221417), ATG16L1 (rs2241880), IL23R (rs2201841) will be performed in leukocyte fraction of blood samples according to the standardized methods. Resulting relative risk will be assessed according to the data on relative risks for each of the above mentioned polymorphisms.
Changes in immunological profile (local) in patients with functional and organic intestinal diseases	2 years	Assessment of local cytokine profile by Human Cytokine Screening panel Bio-plex Pro (27 cytokines, concentrations measured in pg/ml). Local cytokine profile will be assessed in gut biopsy lyophilisate. All cytokine concentrations will be measured in pg/ml.
Changes in functional parameter - ARM in patients with functional and organic intestinal diseases	2 years	Instrumental assessment of ARM during functional examination. The procedure is performed according to standardized IAPWG manometry protocol (2020). The measurement will be performed in mmHg.
Changes in functional parameter - RST in patients with functional and organic intestinal diseases	2 years	Instrumental assessment of RST during functional examination. This is the procedure that assesses rectal sensitivity to distension utilizing the balloon attached to the catheter tip. The procedure is performed according to standardized IAPWG manometry protocol (2020). The measurement will be performed in mls.; Quantitative measurement of balloon volume is recorded for each of the three patient-reported sensory thresholds: first constant sensation volume (FCSV), desire to defecate volume (DDV) and maximum tolerated volume (MTV).

Trial Locations

Locations (2)

Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency; 🇷🇺 Moscow, Russian Federation

Moscow State University of Medicine and Dentistry; 🇷🇺 Moscow, Russian Federation