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

Sponsor

Moscow State University of Medicine and Dentistry (Other)

Overall Status

Recruiting

CT.gov ID

NCT05277662

Collaborator

(none)

120

Enrollment

Locations

Arm

19.4

Anticipated Duration (Months)

Patients Per Site

3.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Diseases Irritable Bowel Syndrome Healthy Volunteers	Diagnostic Test: cell and molecular diagnostics in accordance with functional test results	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Biomedical Experimental Study for Precise Diagnostics of Functional and Organic Intestinal Pathology Based on Cellular and Molecular Profiling

Actual Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

May 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Precision diagnostics profiling 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.	Diagnostic Test: cell and molecular diagnostics in accordance with functional test results Procedure: Anorectal manometry (ARM) Studies are performed in the left lateral position with the hips and knees of the subject flexed. Manometric sensor records circumferential pressure. The base of the rectal balloon attached to the ARM catheter is sited 3-5 cm above the upper border of the anal canal, to prevent the balloon impinging upon the anal canal during inflation. The most distal recording sensor is external to anal verge. If any pain or discomfort is experienced, the probe is immediately withdrawn. Procedure: Rectal sensory test (RST) The test is also performed in the left lateral position with hips and knees flexed. Studies are conducted with either an integrated balloon on the manometric probe or with a separate system. Balloon capacity is no less than 400 mls and all components are latex-free. Insufflation is always performed with air. For ramp distension, the rate should be between 1 and 5 mL/s, and for phasic distension, inflation rate should be set at 10 mL/s (C1).

Arm

Intervention/Treatment

Experimental: Precision diagnostics profiling

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.

Diagnostic Test: cell and molecular diagnostics in accordance with functional test results

Procedure: Anorectal manometry (ARM) Studies are performed in the left lateral position with the hips and knees of the subject flexed. Manometric sensor records circumferential pressure. The base of the rectal balloon attached to the ARM catheter is sited 3-5 cm above the upper border of the anal canal, to prevent the balloon impinging upon the anal canal during inflation. The most distal recording sensor is external to anal verge. If any pain or discomfort is experienced, the probe is immediately withdrawn. Procedure: Rectal sensory test (RST) The test is also performed in the left lateral position with hips and knees flexed. Studies are conducted with either an integrated balloon on the manometric probe or with a separate system. Balloon capacity is no less than 400 mls and all components are latex-free. Insufflation is always performed with air. For ramp distension, the rate should be between 1 and 5 mL/s, and for phasic distension, inflation rate should be set at 10 mL/s (C1).

Outcome Measures

Primary Outcome Measures

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 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 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 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).
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency	Moscow		Russian Federation	119435
2	Moscow State University of Medicine and Dentistry	Moscow		Russian Federation	127473