search
Back to results

Role of Intestinal Protozoa and Helminths in the Course of Ulcerative Colitis

Primary Purpose

Ulcerative Colitis, Ulcerative Colitis Exacerbation, Protozoan Infections

Status
Active
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
parasitological diagnostics (coproscopy)
Nitazoxanide 500Mg Oral Tablet
Mesalazine 250Mg Tablet and nitazoxanide 500Mg Oral Tablet
Mesalazine 250Mg
Placebo tabletes
Sponsored by
Research Institute of Epidemiology, Microbiology and Infectious Diseases, Uzbekistan
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis focused on measuring ulcerative colitis, helminths, intestinal protozoan, nitazoxanide

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Patients with ulcerative colitis before therapy and surgery
  • Residents of Tashkent region which does not have any complaints from the gastrointestinal tract (control group)

Exclusion Criteria:

  • Patients with a diagnosis of Crohn's disease
  • Patients with a toxic megacolon,
  • Patients with a abdominal abscess, -
  • Patients with a symptomatic colonic stricture,
  • Patients with a stoma,
  • Patients with a a history of colectomy,
  • An increased risk of infectious complications (e.g. as a result of recent pyogenic infection, enteric pathogens detected on stool analysis, active or latent tuberculosis, immunodeficiency, hepatitis B or C, or recent live vaccination),
  • Clinically meaningful laboratory abnormalities,
  • Pregnancy or lactation,
  • An unstable or uncontrolled medical disorder,
  • An anticipated requirement for major surgery,
  • Colonic dysplasia or adenomas,
  • Malignant neoplasms.
  • Patients which operated,
  • Ever used immunosuppressants or biological drugs
  • In the presence of pathologic bacteria in gut microbiota, including Clostridium difficile, Salmonella spp, Shigella spp, Campylobacter spp, Yersinia spp, and Mycobacteria.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Active Comparator

    No Intervention

    Active Comparator

    Placebo Comparator

    Active Comparator

    Arm Label

    Patients with ulcerative colitis

    Participants (control group)

    UC patients (cohort 1)

    UC patients (cohort 2)

    UC patients (cohort 3)

    Arm Description

    Patients with ulcerative colitis in this group will take nitazoxanide per os

    only parasitological diagnostics will be performed in this group to compare the prevalence of some representatives of the microbiota

    Patients with ulcerative colitis in this group will take standart therapy (mesalazin)

    Patients with ulcerative colitis in this group will take placebo tabletes

    Patients with ulcerative colitis in this group will take combination standart therapy with nitazoxanide

    Outcomes

    Primary Outcome Measures

    Prevalence of intestinal helminths in patients with ulcerative colitis and association with pathogenesis.
    In this study we expect to find intestinal helminths in patients with ulcerative colitis and determine their role in the development and course of ulcerative colitis
    Prevalence of Lamblia intestinalis and Cryptosporidium parvum in patients with ulcerative colitis and association with pathogenesis
    In this study we expect to find pathogenic protozoa in patients with ulcerative colitis and determine their role in the development of ulcerative colitis
    Prevalence of intestinal protozoa (commensals) in patients with ulcerative colitis and association with pathogenesis
    In this study we are going to determine their prevalence and role in the development of ulcerative colitis
    Efficiency of antiparasitic therapy with nitazoxanide in ulcerative colitis patients infected with B. hominis
    Reduction of intensity or eradication of B. hominis in stool samples of patients with ulcerative colitis
    Efficiency of combination therapy with nitazoxanide and mesalazine in ulcerative colitis patients infected with B. hominis
    Reduction of intensity or eradication of B. hominis in stool samples of patients with ulcerative colitis
    Efficiency of monotherapy with mesalazine in ulcerative colitis patients infected with B. hominis
    Reduction of intensity or eradication of B. hominis in stool samples of patients with ulcerative colitis
    Clinical efficiency of antiparasitic therapy with nitazoxanide in ulcerative colitis patients infected with B. hominis
    A positive/negative clinical response of disease in ulcerative colitis patients
    Clinical efficiency of combination therapy with nitazoxanide and mesalazine in ulcerative colitis patients infected with B. hominis
    A positive/negative clinical response of disease in ulcerative colitis patients
    Clinical efficiency of monotherapy with mesalazine in ulcerative colitis patients infected with B. hominis
    A positive/negative clinical response of disease in ulcerative colitis patients

    Secondary Outcome Measures

    Full Information

    First Posted
    February 8, 2018
    Last Updated
    March 1, 2023
    Sponsor
    Research Institute of Epidemiology, Microbiology and Infectious Diseases, Uzbekistan
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03441893
    Brief Title
    Role of Intestinal Protozoa and Helminths in the Course of Ulcerative Colitis
    Official Title
    Role of Intestinal Protozoa and Helminths in the Course of Ulcerative Colitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Active, not recruiting
    Study Start Date
    January 1, 2015 (Actual)
    Primary Completion Date
    July 1, 2025 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Research Institute of Epidemiology, Microbiology and Infectious Diseases, Uzbekistan

    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
    Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract of unknown etiology. UC is characterized by recurring episodes of inflammation limited to mucosal and submucosal layers of the colon. The object of the present study was to determine the prevalence of intestinal protozoa and helminthes in UC patients, and the role of this changes in aetiopathogenesis of diseases. Patients will be examined before and after therapy. Parasites and protozoa prevalence and intensity will be detected by triple coproscopy.Microbiological study will be conducted before therapy for detection pathogenic bacteria only from UC patients infected with B. hominis . If intestinal pathogenic bacteria are found, participants will be excluded from further investigation.
    Detailed Description
    The prospective cohort and randomized, double-blind, placebo controlled study will be conducted on the basis of Research Institute of Epidemiology, Microbiology and Infectious Diseases and Coloproctology department of the Republic clinical hospital №1, Ministry of Public Health of the Republic of Uzbekistan. Participants Diagnosis of UC will be confirmed using standard clinical, endoscopic, radiographic, and pathological criteria according to the Montreal classification of extent and severity of ulcerative colitis (Silverberg MS et al. 2006). UC categories include proctitis, left-sided colitis, and extensive colitis or pancolitis. Activity of the disease will be measured by Mayo Clinic score that consists of 4 items: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy, and patient's functional assessment (D'Haens G et al. 2007). The disease duration will be measured in years from the first time of symptoms onset. UC patients hospitalized in coloproctology department of Republic clinical hospital №1 will be examined before surgery and receiving of medications. Additional cohort groups: the 1st one will include UC patients infected with B. hominis which will be examined before and after taking nitazoxanide (monotherapy), the 2nd group will include UC patients infected with B. hominis before and after taking nitazoxanide and mesalazine (combination therapy) and 3rd one - patients with UC infected with B. hominis before and after taking mesalazine (monotherapy). The control group will include residents of Tashkent region without any complaints from the gastrointestinal tract, who will apply to the clinic for planned medical examinations. Suggested age of the population from 17 to 90 years Exclusion criteria Patients with diagnosis of Crohn's disease will be excluded from the analysis. Other exclusion criteria are toxic megacolon, abdominal abscess, symptomatic colonic stricture, stoma, a history of colectomy, an increased risk of infectious complications (e.g. as a result of recent pyogenic infection, enteric pathogens detected in microbiological stool analysis, active or latent tuberculosis, immunodeficiency, hepatitis B or C, or recent live vaccination), clinically meaningful laboratory abnormalities, pregnancy or lactation, unstable or uncontrolled medical disorders, an anticipated requirements for major surgery, colonic dysplasia or adenomas, and malignant neoplasms. For additional groups except the above mentioned the followed patients will be excluded: individuals who were operated, ever used immunosuppressants or biological drugs, infected with intestinal pathologenic bacteria, including Clostridium difficile, Salmonella spp, Shigella spp, Campylobacter spp, Yersinia spp, and Mycobacteria. Parasitological method Collection of stool samples. Three stool samples for parasitological examination will be taken from both control subjects and UC patients at 2 days interval before therapy (all participants) and in the 2nd week of monotherapy therapy with nitazoxanide, nitazoxanide in combination with mesalazine and monotherapy with mesalazine and in 6th and 12th weeks from beginning of the therapy. Stool samples (1-2g.) will be collected in individual containers, with 5 ml of Turdiev's preservative provided conservation and staining of proozoa cysts and eggs of worms for a year. The Turdiev's preservative includes: 80 ml of 0.2% aqueous solution of sodium nitrite, 10 ml of formaldehyde, 2 ml of glycerin, 8 ml of Lugol's solution, 250 ml of distilled water. Stool samples (1-2g.) for detection of C. parvum (Cryptosporidium parvum) will be collected in individual empty containers no less 1 hour before parasitological examination. Microscopy. Parasitological diagnosis will be performed by triple coproscopy using formalin - ethyl acetate concentration technique [Truant AL, Elliott SH] and iodine stained smears [King M.]. For preparations staining Lugol's solution will be used. The intensity of protozoa will be estimated by the number of protozoa in the field of view (ocular x10, objective x40) in iodine stained smears taken before application of formalin - ethyl acetate concentration technique, the number of protozoa will be calculated at least in 10 fields of view. 1-2, 3-4 and 5-6 microorganisms in a field of view were considered as infection of low, mean and high intensity respectively. For detection of C. parvum modified Ziehl - Neelsen method [Henricksen SA, Pohlenz JF] will be used for staining the preparations. The stained smears will be scanned with ×100 oil immersion lens for the presence of C. parvum. Microbiological methods Microbiological methods wil be conducted for detection pathogenic bacteria, including Clostridium difficile, Salmonella spp, Shigella spp, Campylobacter spp, Yersinia spp, and Mycobacteria only from UC patients infected with B. hominis before therapy. If intestinal pathogenic bacteria are detected participants will be excluded from further investigation. Collection of stool samples. Fecal samples will be collected from UC patients infected with B. hominis before therapy in sterile, wide-mouth, screw capped containers and immediately transferred to the laboratory, preferably within 2 h. Specimens will be processed for microscopy, anaerobic and aerobic culture, and ELISA (only for Clostridium difficile). Procedures Parasitological examination in UC patients and population will be provided. Additional UC patients infected with B. hominis will be divided into 3 cohorts, in double-blinded fashion, to receive 1 of the following treatments: (1) patients with UC infected with B. hominis will be treated with nitazoxanide, 1.0 g/daily (two pills) twice over orally for 14 consecutive days; (2) UC patients infected with B. hominis will be treated with nitazoxanide by a 1.0 g/day (one pill - 500 mg) twice over orally and mesalazine 1.5 g/day (one pill - 500 mg) three times a day orally for 14 consecutive days; (3) patients with UC infected B. hominis will be treated with mesalazine ≥3 g/day (one pill - 500 mg) three times a day orally for 14 consecutive days. Except drugs patients of all three groups adhered to the diet. The purpose of follow-up was to monitor compliance with medications and to record response to therapy, adverse events, and recurrence of symptoms. Other detected pathogenic protozoan and helminthes was treated by standard dosage of antiparasitic drugs. Follow-up The study was conducted in two stages. At the first stage parasitological examination of patients with UC before treatment and population will be provided . At the second stage of the study in patients with UC infected with B. hominis drugs with anti Blastocystis activity will be applied as well as monitoring of therapy efficiency. Parasitological, microbiological, clinical and endoscopic examination will be conducted before therapy and at the 2nd, 6th and 12th weeks. At each visit, a Mayo Clinic score will be calculated and intensity/elimination of B. hominis will be determined. Outcome measures The outcome measures of therapy are : eradication/ reduction of intensity of B. hominis infection and a clinical response of UC patients at the 2nd, 6th and 12th weeks will be defined as a reduction in the Mayo Clinic score.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ulcerative Colitis, Ulcerative Colitis Exacerbation, Protozoan Infections, Helminth Infection
    Keywords
    ulcerative colitis, helminths, intestinal protozoan, nitazoxanide

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    300 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Patients with ulcerative colitis
    Arm Type
    Active Comparator
    Arm Description
    Patients with ulcerative colitis in this group will take nitazoxanide per os
    Arm Title
    Participants (control group)
    Arm Type
    No Intervention
    Arm Description
    only parasitological diagnostics will be performed in this group to compare the prevalence of some representatives of the microbiota
    Arm Title
    UC patients (cohort 1)
    Arm Type
    Active Comparator
    Arm Description
    Patients with ulcerative colitis in this group will take standart therapy (mesalazin)
    Arm Title
    UC patients (cohort 2)
    Arm Type
    Placebo Comparator
    Arm Description
    Patients with ulcerative colitis in this group will take placebo tabletes
    Arm Title
    UC patients (cohort 3)
    Arm Type
    Active Comparator
    Arm Description
    Patients with ulcerative colitis in this group will take combination standart therapy with nitazoxanide
    Intervention Type
    Diagnostic Test
    Intervention Name(s)
    parasitological diagnostics (coproscopy)
    Intervention Description
    Three stool samples for parasitological examination will be taken from ulcerative colitis patients at 1-2 days interval.
    Intervention Type
    Drug
    Intervention Name(s)
    Nitazoxanide 500Mg Oral Tablet
    Intervention Description
    Tab. nitazoxanide by a 1.0 g/day (two pills) twice over orally for 14 consecutive days
    Intervention Type
    Drug
    Intervention Name(s)
    Mesalazine 250Mg Tablet and nitazoxanide 500Mg Oral Tablet
    Intervention Description
    Tab. nitazoxanide by a 1.0 g/day (one pill - 500 mg) twice over orally and mesalazine 1.5 g/day (one pill - 500 mg) three times a day orally for 14 consecutive days
    Intervention Type
    Drug
    Intervention Name(s)
    Mesalazine 250Mg
    Intervention Description
    Tab. mesalazine ≥3 g/day (one pill - 500 mg) three times a day orally for 14 consecutive days
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo tabletes
    Intervention Description
    Tab. Placebo (shugar pills) will be given to the participants
    Primary Outcome Measure Information:
    Title
    Prevalence of intestinal helminths in patients with ulcerative colitis and association with pathogenesis.
    Description
    In this study we expect to find intestinal helminths in patients with ulcerative colitis and determine their role in the development and course of ulcerative colitis
    Time Frame
    up to 36 months
    Title
    Prevalence of Lamblia intestinalis and Cryptosporidium parvum in patients with ulcerative colitis and association with pathogenesis
    Description
    In this study we expect to find pathogenic protozoa in patients with ulcerative colitis and determine their role in the development of ulcerative colitis
    Time Frame
    up to 36 months
    Title
    Prevalence of intestinal protozoa (commensals) in patients with ulcerative colitis and association with pathogenesis
    Description
    In this study we are going to determine their prevalence and role in the development of ulcerative colitis
    Time Frame
    up to 36 months
    Title
    Efficiency of antiparasitic therapy with nitazoxanide in ulcerative colitis patients infected with B. hominis
    Description
    Reduction of intensity or eradication of B. hominis in stool samples of patients with ulcerative colitis
    Time Frame
    up to 24 months
    Title
    Efficiency of combination therapy with nitazoxanide and mesalazine in ulcerative colitis patients infected with B. hominis
    Description
    Reduction of intensity or eradication of B. hominis in stool samples of patients with ulcerative colitis
    Time Frame
    up to 24 months
    Title
    Efficiency of monotherapy with mesalazine in ulcerative colitis patients infected with B. hominis
    Description
    Reduction of intensity or eradication of B. hominis in stool samples of patients with ulcerative colitis
    Time Frame
    up to 24 months
    Title
    Clinical efficiency of antiparasitic therapy with nitazoxanide in ulcerative colitis patients infected with B. hominis
    Description
    A positive/negative clinical response of disease in ulcerative colitis patients
    Time Frame
    up to 24 months
    Title
    Clinical efficiency of combination therapy with nitazoxanide and mesalazine in ulcerative colitis patients infected with B. hominis
    Description
    A positive/negative clinical response of disease in ulcerative colitis patients
    Time Frame
    up to 24 months
    Title
    Clinical efficiency of monotherapy with mesalazine in ulcerative colitis patients infected with B. hominis
    Description
    A positive/negative clinical response of disease in ulcerative colitis patients
    Time Frame
    up to 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    90 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Patients with ulcerative colitis before therapy and surgery Residents of Tashkent region which does not have any complaints from the gastrointestinal tract (control group) Exclusion Criteria: Patients with a diagnosis of Crohn's disease Patients with a toxic megacolon, Patients with a abdominal abscess, - Patients with a symptomatic colonic stricture, Patients with a stoma, Patients with a a history of colectomy, An increased risk of infectious complications (e.g. as a result of recent pyogenic infection, enteric pathogens detected on stool analysis, active or latent tuberculosis, immunodeficiency, hepatitis B or C, or recent live vaccination), Clinically meaningful laboratory abnormalities, Pregnancy or lactation, An unstable or uncontrolled medical disorder, An anticipated requirement for major surgery, Colonic dysplasia or adenomas, Malignant neoplasms. Patients which operated, Ever used immunosuppressants or biological drugs In the presence of pathologic bacteria in gut microbiota, including Clostridium difficile, Salmonella spp, Shigella spp, Campylobacter spp, Yersinia spp, and Mycobacteria.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    33188747
    Citation
    Toychiev A, Navruzov B, Pazylova D, Davis N, Badalova N, Osipova S. Intestinal protozoa and helminths in ulcerative colitis and the influence of anti-parasitic therapy on the course of the disease. Acta Trop. 2021 Jan;213:105755. doi: 10.1016/j.actatropica.2020.105755. Epub 2020 Nov 11.
    Results Reference
    result
    Links:
    URL
    https://pubmed.ncbi.nlm.nih.gov/33188747/
    Description
    Article in Pubmed

    Learn more about this trial

    Role of Intestinal Protozoa and Helminths in the Course of Ulcerative Colitis

    We'll reach out to this number within 24 hrs