Colonoscopic Probiotics Spray in Irritable Bowel Syndrome

NCT ID: NCT05864716

Last Updated: 2024-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-01

Study Completion Date

2026-04-30

Brief Summary

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Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal (GI) tract characterized by chronic abdominal pain and altered bowel habits without organic disease. IBS is associated with substantial costs to patients, healthcare system and society in terms of increased health care expenditures, loss of work productivity and decrease in quality of life (QoL). Multiple factors play an important role in the pathogenesis of IBS, including disturbed gut microbiota (dysbiosis). Fecal microbiota transplantation (FMT) and probiotics administration can manipulate the disturbed intestinal microbiota. According to previous studies, inconsistent efficacy of oral probiotic administration was reported. FMT may have good and lasting efficacy, but the donor selection and route of administration are still issues. Direct delivery of probiotics into the colon by colonoscopy can ensure sufficient microbiota distribution in the colon, so faster and better efficacy may be expected. Therefore, this study is aimed toward validating the efficacy and safety of the colonoscopic probiotics-spray in IBS treatment.

Patients diagnosed with irritable bowel syndrome by Rome IV criteria will be enrolled in this randomized double-blind double-dummy parallel controlled study. The enrolled patients will be randomly assigned to the probiotics-spray (PS) group and the probiotics-oral (PO) group, respectively. The patients in the PS group will receive colonoscopic spray of probiotics once followed by oral placebo for 5 days, while the patients in the PO group will receive colonoscopic spray of placebo once followed by oral probiotics divided into 5 days. Then all of the patients will take the same dose of oral probiotics until 4 weeks. This study will evaluate the efficacy between the PS group and the PO group. Moreover, this study will compare the difference in fecal microbiota changes and safety between these two groups.

Detailed Description

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Irritable bowel syndrome (IBS) is a common chronic functional disorder of the gastrointestinal (GI) tract characterized by chronic abdominal pain and altered bowel habits without organic disease. The global prevalence of IBS in 2012 was estimated to be 11.2%. The overall incidence of IBS in Taiwan was 106.54 per 10000 population from 2012 to 2018, which is similar to the global prevalence. IBS is associated with substantial costs to patients, healthcare system and society in terms of increased health care expenditures, loss of work productivity and decrease in quality of life (QoL). There is no definite treatment for IBS, and current available treatments are mainly directed at symptom relief.

The cause of IBS is not yet known; however, multiple factors play an important role in the pathogenesis of IBS, such as disturbed gut microbiota (dysbiosis), altered enteroendocrine cells, previous infections, genetics and diet. Treatment guidelines recommend medications focused on IBS symptoms, diets low in fermentable types of oligosaccharides, and the use of probiotics. Probiotics are live microorganisms using in dietary as supplemental products. They have the beneficial effect on gut microenvironment, and may be an effective treatment for global symptoms and abdominal pain in IBS. Probiotics were defined as live microbial feed supplements that benefit the host by improving the intestinal microbial balance. The strains most frequently used as probiotics belong to the genera Bifidobacterium and Lactobacillus. Some probiotics have anti-inflammatory activity while others can modulate visceral hypersensitivity. However, inconsistent efficacy of probiotic administration was reported in the previous literature. Hod K, et al. conducted a double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS, but they did not demonstrate superiority of probiotics over placebo. However, some meta-analysis revealed efficacy of probiotics for treatment of IBS. A meta-analysis published in 2020 concluded the RR of IBS symptoms improvement or response with probiotics treatment was 1.52, however, with high heterogeneity. The duration, dose and single or combination of probiotics vary and need to be further evaluated. A review of probiotics in IBS suggests that probiotic supplements have a delayed effect in the improvement of IBS symptoms. Khodadoostan M, et al. conducted a trial to evaluate the effect of probiotic administration immediately and 1 month after colonoscopy in diarrhea-predominant IBS patients, which revealed the use of probiotics had the beneficial effect on IBS symptoms. Furthermore, it can be said that reductions in symptoms and pain in the two treatment groups were not significantly different, but after 6 months of treatment, the effect of probiotics in patients who immediately use it after colonoscopy was more visible and more stable. Niu HL, et al studied the efficacy and safety of probiotics in patients with irritable bowel syndrome based on 35 randomized controlled trials, which reveals supplementation with a multi-strain probiotic has greater potential to improve IBS symptoms than a single strain, and there is also a trend toward a beneficial effect of Bifidobacterium on global IBS symptoms and pain scores. Therefore, investigators propose a trial to evaluate the efficacy of the use of multi-strain probiotics including Bifidobacterium which is immediately used after colonoscopy for IBS treatment.

It is novel to conduct the study to compare the efficacy and safety of probiotics which are delivered directly via colonoscopy and oral administration. The amount of stool for FMT is 30 to 100 grams; thus, around 1012 to 1013 CFU bacteria will be transplanted in an FMT procedure. In this trial, the investigators will transplant 2x1011 CFU multi-strain probiotics into the colon via colonoscopic spray. Probiotics may be safer than FMT due to minimal risk of transmission of pathogenic organisms. It is also easier to prepare probiotics than feces from a superdonor. If it works, colonoscopic probiotics spray may replace FMT in clinical practice.

Conditions

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Effect of Drug

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Placebo powder was applied in the control group, and the powder was prepared in probiotics factory, which was blind to both patients and caregivers.

Study Groups

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probiotics-spray (PS) group

In the PS group, 1 vial of multi-strain probiotics powder via colonoscopic spray is performed once, followed by five-days of two oral placebo capsules daily. After the five-day treatment, the 2nd fecal sample will be collected. Both groups will receive a 23-day course of oral probiotics (two capsules twice daily) subsequently. The patients were asked to keep a diary to record bowel habits and register any adverse events. The 3rd fecal sample will be collected 28 days after the colonoscopy. The questionnaires will be completed 28 days and 84 days after the colonoscopy to assess responses of treatment. Polyethylene glycol and loperamide were allowed during the intervention as the rescue medication.

Group Type EXPERIMENTAL

Colonscopic probiotics spray

Intervention Type BIOLOGICAL

20g of multi-strain probiotics powder via colonoscopic spray. The probiotic used in this study is SynPro-15G, which has 15 probiotics, including Bacillus coagulans BC1031, Bifidobacterium bifidum BB14, Bifidobacterium breve BR18, Bifidobacterium animalis subsp. lactis BAL06, Bifidobacterium longum (B. longum) BL986, Lactobacillus acidophilus LA1063, Lactobacillus casei LC122, Lactobacillus delbrueckii subsp. lactis LDL114, Lactobacillus fermentum LF26, Lactobacillus helveticus LH43, Lactobacillus paracasei LPC12, Lactobacillus plantarum LP198, Lactobacillus reuteri LR21, Lactobacillus rhamnosus LRH10, and Streptococcus thermophilus ST37 at a concentration of 2x1010 CFU/g (Synbiotech Corp., Kaohsiung, Taiwan). SynPro-15G is made either as a vial of powder (2x1011 CFU /vial) for colonoscopic spray or as a capsule (2x1010 CFU/capsule) for oral intake.

probiotics-oral (PO) group

In the PO group, 1 vial of placebo powder via colonoscopic spray is performed once, followed by five-days of two oral probiotics capsules daily. After the five-day treatment, the 2nd fecal sample will be collected. Both groups will receive a 23-day course of oral probiotics (two capsules twice daily) subsequently. The patients were asked to keep a diary to record bowel habits and register any adverse events. The 3rd fecal sample will be collected 28 days after the colonoscopy. The questionnaires will be completed 28 days and 84 days after the colonoscopy to assess responses of treatment. Polyethylene glycol and loperamide were allowed during the intervention as the rescue medication.

Group Type ACTIVE_COMPARATOR

Colonscopic probiotics spray

Intervention Type BIOLOGICAL

20g of multi-strain probiotics powder via colonoscopic spray. The probiotic used in this study is SynPro-15G, which has 15 probiotics, including Bacillus coagulans BC1031, Bifidobacterium bifidum BB14, Bifidobacterium breve BR18, Bifidobacterium animalis subsp. lactis BAL06, Bifidobacterium longum (B. longum) BL986, Lactobacillus acidophilus LA1063, Lactobacillus casei LC122, Lactobacillus delbrueckii subsp. lactis LDL114, Lactobacillus fermentum LF26, Lactobacillus helveticus LH43, Lactobacillus paracasei LPC12, Lactobacillus plantarum LP198, Lactobacillus reuteri LR21, Lactobacillus rhamnosus LRH10, and Streptococcus thermophilus ST37 at a concentration of 2x1010 CFU/g (Synbiotech Corp., Kaohsiung, Taiwan). SynPro-15G is made either as a vial of powder (2x1011 CFU /vial) for colonoscopic spray or as a capsule (2x1010 CFU/capsule) for oral intake.

Interventions

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Colonscopic probiotics spray

20g of multi-strain probiotics powder via colonoscopic spray. The probiotic used in this study is SynPro-15G, which has 15 probiotics, including Bacillus coagulans BC1031, Bifidobacterium bifidum BB14, Bifidobacterium breve BR18, Bifidobacterium animalis subsp. lactis BAL06, Bifidobacterium longum (B. longum) BL986, Lactobacillus acidophilus LA1063, Lactobacillus casei LC122, Lactobacillus delbrueckii subsp. lactis LDL114, Lactobacillus fermentum LF26, Lactobacillus helveticus LH43, Lactobacillus paracasei LPC12, Lactobacillus plantarum LP198, Lactobacillus reuteri LR21, Lactobacillus rhamnosus LRH10, and Streptococcus thermophilus ST37 at a concentration of 2x1010 CFU/g (Synbiotech Corp., Kaohsiung, Taiwan). SynPro-15G is made either as a vial of powder (2x1011 CFU /vial) for colonoscopic spray or as a capsule (2x1010 CFU/capsule) for oral intake.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Moderate-to-severe IBS symptoms, as indicated by a score of ≥175 on the IBS Severity Scoring System (IBS-SSS).

Exclusion Criteria

* Presence of immune deficiency or treatment with immune-modulating medication.
* Pregnant or lactating.
* Severe psychiatric disorder, or alcohol or drug abuse.
* Use of probiotics or treatment with antibiotics within 4 weeks prior to study entry.
Minimum Eligible Age

20 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cheng-Kung University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Hsueh-Chien Chiang, M.D.

Role: CONTACT

Po-Jun Chen, M.D.

Role: CONTACT

References

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Other Identifiers

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A BR 111 0 47

Identifier Type: -

Identifier Source: org_study_id

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