Effect of Probiotics on Gut Microbiota During the Helicobacter Pylori Eradication

Helicobacter Pylori Infection Clinical Trial

Official title:

Effect of Probiotics on Gut Microbiota During the Helicobacter Pylori Eradication: a Randomized Double-blind Placebo-controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05662514
• Other study ID #: KYLL-202210-011
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 15, 2023
• Est. completion date: January 15, 2024

Study information

• Verified date: December 2022
• Source: Qilu Hospital of Shandong University
• Contact: Tao Zhou, Dr
• Phone: 18560086097
• Email: lyynqj[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Helicobacter pylori (H. pylori) is still infecting more than half of the population in many countries, although the prevalence is decreasing. As a main cause of chronic gastritis, peptic ulcer, and malignant gastric tumors, H. pylori places a heavy burden on developing countries and regions with high infection rate. In the last decade, the eradication rates of conventional regimens based on proton pump inhibitors (PPIs) plus antibiotics have been decreasing. Antibiotic resistance and decrease of drug compliance caused by adverse effects were the two main reasons for eradication failure. Moreover, H. pylori treatment causes dysbiosis of gut microbiota and increases the expression of antibiotic resistance gene. Therefore, eradication of H. pylori is facing a great challenge, and effective and safe methods are needed.

To reduce adverse effects, improve drug compliance and increase eradication rates, certain probiotics were added to conventional regimens in several clinical studies. Probiotics were more or less shown to reduce adverse effects in the vast majority of clinical studies, but whether probiotics can improve the eradication rate of H. pylori remains controversial. Meanwhile, several studies focusing on the impact of probiotics on gut microbiota during H. pylori eradication have been published recently. Thus, we conducted a randomized, double-blind, placebo-controlled trial aiming to evaluate the effects of probiotics combining with 14-day bismuth quadruple therapy on H. pylori eradication.

Description:

This was a randomized, parallel-group, double-blind and placebo-controlled study. If the subject meets the selection criteria but not the exclusion criteria, and signs an informed consent form, patients were randomly allocated in a 1:1 ratio to receive either the investigational product or placebo along with H. pylori eradication therapy. The randomization sequence was generated using SAS 9.1.3. Eight weeks after the eradication treatment, the subjects will review the 13C-urea breath test, and the researcher records the results. Feces samples, which were taken at the subject's home at the beginning, the end of treatment and 8 weeks after treatment completion, were collected from the patients immediately and stored at -80 °C until analysis. In this study, the influences of antibiotics and combination of probiotics on gut microbiota during H. pylori treatments were investigated using high-throughput sequencing of the 16S rRNA gene.

Patients were required to recall the history of gastrointestinal symptoms at baseline, keep the symptom diaries during the treatment and return the diaries at week 2. Gastrointestinal symptoms were assessed and scored according to the 15-iteem GSRS27 before (week 0) and after quadruple therapy (week 2). Special attention was given to the following symptoms: epigastric pain, heartburn, acid regurgatition, nausea or/and vomiting, abdominal distension, eructation, diarrhea, constipation. Adverse effects outside gastrointestine were also recorded and evaluated.

Compliance with antibiotic therapy and the investigational product was evaluated by means of a patient's diary and product accountability, while compliance with eradication therapy was evaluated through a questionnaire. After all subjects were tested, the eradication rates, adverse reaction rates and patient compliance of each group were calculated.

Patients were evaluated at 4 visits: screening (10-30 days before the baseline visit), baseline, end of treatment/efficacy (14 days after the baseline visit) and follow-up (8 weeks after treatment completion). Patients were diagnosed with one (or more) of three validated methods, 13C-urea breath test, rapid urease test or histology, depending on the clinical situation of the patient. Eradication confirmation test was also performed following standard recommendations: 13C-urea breath test at 8 weeks after treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: January 15, 2024
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients aged 18-70.

2. Patients with H. pylori infection (Positive for rapid urease test or 13C/14C-urea breath test).

3. Patients who have did not receive H. pylori eradication treatment before.

Exclusion Criteria:

1. Patients with serious underlying diseases, such as liver insufficiency (Aspartate aminotransferase or alanine aminotransferase greater than 1.5 times the normal value), renal insufficiency (Cr=2.0mg/dL or glomerular filtration rate <50 ml/min), immunosuppression, malignant tumors, Coronary heart disease or coronary artery stenosis =75%.

2. Patients who are pregnant or lactating or unwilling to take contraceptive measures during the trial.

3. Patients with active gastrointestinal bleeding.

4. Patients with a history of upper gastrointestinal surgery.

5. Patients allergic to treatment drugs.

6. Patients with medication history of bismuth agents, antibiotics, proton pump inhibitor and other drugs which might influence gut microbiota within 3 months.

7. Patients with other behaviors that may increase the risk of illness, such as alcohol and drug abuse.

8. Patients who are unwilling or incapable to provide informed consents.

Related Conditions & MeSH terms

• Gut Microbiota
• Helicobacter Pylori Infection

Intervention

Dietary Supplement:
• Bifidobacterium animalis subsp. lactis BLa80
Test product contain 3 × 109 colony-forming units [CFU] Bifidobacterium animalis subsp. lactis BLa80 strains, for each packet. Subjects ingested one packet (3 g/packet) of Test product per day (2 hours after taking antibiotics in the evening), for 14 days.

Other:
• Placebo
To maintain the blinding, patients in the control group received placebo included in identical packets. Control product per day (2 hours after taking antibiotics), for 14 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Hospital of Shandong University

References & Publications (4)

Guillemard E, Poirel M, Schafer F, Quinquis L, Rossoni C, Keicher C, Wagner F, Szajewska H, Barbut F, Derrien M, Malfertheiner P. A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pyl — View Citation

Nabavi-Rad A, Sadeghi A, Asadzadeh Aghdaei H, Yadegar A, Smith SM, Zali MR. The double-edged sword of probiotic supplementation on gut microbiota structure in Helicobacter pylori management. Gut Microbes. 2022 Jan-Dec;14(1):2108655. doi: 10.1080/19490976.2022.2108655. — View Citation

Yang C, Liang L, Lv P, Liu L, Wang S, Wang Z, Chen Y. Effects of non-viable Lactobacillus reuteri combining with 14-day standard triple therapy on Helicobacter pylori eradication: A randomized double-blind placebo-controlled trial. Helicobacter. 2021 Dec;26(6):e12856. doi: 10.1111/hel.12856. Epub 2021 Oct 10. — View Citation

Yuan Z, Xiao S, Li S, Suo B, Wang Y, Meng L, Liu Z, Yin Z, Xue Y, Zhou L. The impact of Helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults. Helicobacter. 2021 Dec;26(6):e12848. doi: 10.1111/hel.12848. Epub 2021 Aug 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut microbiota	Stool samples were collected at wk0, wk2, and wk10. Patients were instructed to collect stool samples at the medical visit site by using disposable sterile feces collection tubes. Samples were stored at -80? after collection immediately. In this study, the influences of antibiotics and combination of probiotics on gut microbiota during H. pylori treatments were investigated using high-throughput sequencing of the 16S rRNA gene.	Week 0, week 2 and week 10
Secondary	Rate of adverse reactions	Rate of adverse reactions	Week 2 and week 10
Secondary	Patient compliance	Good compliance is defined as the actual dosage is within the range of 80%-100% of the dosage that should be taken.	Week 10