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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05277662
• Other study ID #: CSR-04/21
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2021
• Est. completion date: May 15, 2023

Study information

• Verified date: January 2022
• Source: Moscow State University of Medicine and Dentistry
• Contact: Svetlana Lyamina, Prof.
• Phone: +7 915 018 5006
• Email: svlvs[@]mail.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 15, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Irritable Bowel Syndrome

Intervention

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).

Locations

Country	Name	City	State
Russian Federation	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

Sponsors (1)

Lead Sponsor	Collaborator
Moscow State University of Medicine and Dentistry

Country where clinical trial is conducted

Russian Federation, 

References & Publications (5)

Aziz I, Simrén M. The overlap between irritable bowel syndrome and organic gastrointestinal diseases. Lancet Gastroenterol Hepatol. 2021 Feb;6(2):139-148. doi: 10.1016/S2468-1253(20)30212-0. Epub 2020 Nov 13. Review. — View Citation

Gehart H, Clevers H. Tales from the crypt: new insights into intestinal stem cells. Nat Rev Gastroenterol Hepatol. 2019 Jan;16(1):19-34. doi: 10.1038/s41575-018-0081-y. Review. — View Citation

Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, Whitehead WE, Dumitrascu DL, Fang X, Fukudo S, Kellow J, Okeke E, Quigley EMM, Schmulson M, Whorwell P, Archampong T, Adibi P, Andresen V, Benninga MA, Bonaz B, Bor S, Fernandez LB, Cho — View Citation

Van Malderen K, De Winter BY, De Man JG, De Schepper HU, Lamote K. Volatomics in inflammatory bowel disease and irritable bowel syndrome. EBioMedicine. 2020 Apr;54:102725. doi: 10.1016/j.ebiom.2020.102725. Epub 2020 Apr 21. Review. — View Citation

Wilson JC, Furlano RI, Jick SS, Meier CR. Inflammatory Bowel Disease and the Risk of Autoimmune Diseases. J Crohns Colitis. 2016 Feb;10(2):186-93. doi: 10.1093/ecco-jcc/jjv193. Epub 2015 Oct 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of metabolic profile in patients with functional and organic intestinal diseases	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.	2 years
Primary	Changes in genetic profile in patients with functional and organic intestinal diseases	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.	2 years
Primary	Changes in immunological profile (local) in patients with functional and organic intestinal diseases	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.	2 years
Primary	Changes in immunological profile (systemic) in patients with functional and organic intestinal diseases	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.	2 years
Primary	Changes in functional parameter - RST in patients with functional and organic intestinal diseases	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).	2 years
Primary	Changes in functional parameter - ARM in patients with functional and organic intestinal diseases	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.	2 years