Back to resultsPrecision Diagnostics of Functional and Organic Intestinal Pathology Based on Cellular and Molecular Profiling
Primary Purpose
Inflammatory Bowel Diseases, Irritable Bowel Syndrome, Healthy Volunteers
Status
Recruiting
Phase
Not Applicable
Locations
Russian Federation
Study Type
Interventional
Intervention
cell and molecular diagnostics in accordance with functional test results
Sponsored by
About this trial
This is an interventional basic science trial for Inflammatory Bowel Diseases focused on measuring Inflammatory Bowel Disease, Crohn's disease, Ulcerative colitis, Irritable Bowel Syndrome, Precision diagnostics, Metabolomics, Genomics, Transcriptomics, Immunology
Eligibility Criteria
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
Sites / Locations
- Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological AgencyRecruiting
- Moscow State University of Medicine and DentistryRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Precision diagnostics profiling
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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).
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT05277662
First Posted
January 13, 2022
Last Updated
March 11, 2022
Sponsor
Moscow State University of Medicine and Dentistry
1. Study Identification
Unique Protocol Identification Number
NCT05277662
Brief Title
Precision Diagnostics of Functional and Organic Intestinal Pathology Based on Cellular and Molecular Profiling
Official Title
Biomedical Experimental Study for Precise Diagnostics of Functional and Organic Intestinal Pathology Based on Cellular and Molecular Profiling
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
May 15, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Moscow State University of Medicine and Dentistry
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Bowel Diseases, Irritable Bowel Syndrome, Healthy Volunteers
Keywords
Inflammatory Bowel Disease, Crohn's disease, Ulcerative colitis, Irritable Bowel Syndrome, Precision diagnostics, Metabolomics, Genomics, Transcriptomics, Immunology
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Precision diagnostics profiling
Arm Type
Experimental
Arm Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
cell and molecular diagnostics in accordance with functional test results
Intervention Description
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).
Primary Outcome Measure Information:
Title
Changes of metabolic profile in patients with functional and organic intestinal diseases
Description
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.
Time Frame
2 years
Title
Changes in genetic profile in patients with functional and organic intestinal diseases
Description
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.
Time Frame
2 years
Title
Changes in immunological profile (local) in patients with functional and organic intestinal diseases
Description
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.
Time Frame
2 years
Title
Changes in immunological profile (systemic) in patients with functional and organic intestinal diseases
Description
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.
Time Frame
2 years
Title
Changes in functional parameter - RST in patients with functional and organic intestinal diseases
Description
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).
Time Frame
2 years
Title
Changes in functional parameter - ARM in patients with functional and organic intestinal diseases
Description
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.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Svetlana Lyamina, Prof.
Phone
+7 915 018 5006
Email
svlvs@mail.ru
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Igor Maev, Acad.the RAS
Organizational Affiliation
Moscow State University of Medicine and Dentistry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency
City
Moscow
ZIP/Postal Code
119435
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalia Zakharzhevskaya, PhD
Phone
+7 916 853 4351
Email
natazaha@gmail.com
Facility Name
Moscow State University of Medicine and Dentistry
City
Moscow
ZIP/Postal Code
127473
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Svetlana Lyamina, Prof
Phone
+7 915 018 5006
Email
svlvs@mail.ru
First Name & Middle Initial & Last Name & Degree
Igor Maev, Acad.the RAS
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32330874
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.
Results Reference
result
PubMed Identifier
33189181
Citation
Aziz I, Simren 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.
Results Reference
result
PubMed Identifier
30429586
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.
Results Reference
result
PubMed Identifier
32294476
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, Choi SC, Corazziari ES, Francisconi C, Hani A, Lazebnik L, Lee YY, Mulak A, Rahman MM, Santos J, Setshedi M, Syam AF, Vanner S, Wong RK, Lopez-Colombo A, Costa V, Dickman R, Kanazawa M, Keshteli AH, Khatun R, Maleki I, Poitras P, Pratap N, Stefanyuk O, Thomson S, Zeevenhooven J, Palsson OS. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021 Jan;160(1):99-114.e3. doi: 10.1053/j.gastro.2020.04.014. Epub 2020 Apr 12.
Results Reference
result
PubMed Identifier
26507860
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.
Results Reference
result
Learn more about this trial
Precision Diagnostics of Functional and Organic Intestinal Pathology Based on Cellular and Molecular Profiling
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