Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05399862 |
| Other study ID # |
FF-2021-004 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 24, 2020 |
| Est. completion date |
January 10, 2022 |
Study information
| Verified date |
May 2022 |
| Source |
Universiti Kebangsaan Malaysia Medical Centre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a prospective, randomised, double-blind, placebo-controlled trial involving newly
diagnosed Helicobacter pylori (H. pylori) patients. Patients will be prescribed with standard
triple therapy for 2 weeks and supplemented with either probiotic (Lactobacillus reuteri DSM
17648) or placebo for 4 weeks. In this study, we are investigating the effect of
Lactobacillus reuteri in H. pylori eradication; mainly in improving eradication rate,
ameliorating gastrointestinal symptoms and reducing adverse effects of antibiotics. We
hypothesised that in H. pylori patients receiving Lactobacillus reuteri as adjunct treatment,
there will be an improvement in H. pylori eradication rate as well as reduction of
gastrointestinal symptoms and treatment adverse effects.
Description:
The prime discovery of Helicobacter pylori (H. pylori) in chronic gastritis patients by
Marshall and Warren in 1982 has geared a frenetic pace in H. pylori research. H. pylori is a
helix-shaped microaerophilic gram negative bacterium colonising gastric epithelium leading to
disruption of protective mucosal layer by inflammatory process and gastric acid secretion.
H. pylori remains as one of the commonest bacterial pathogens causing chronic infection in
the adult population with at least 50% of the global population being infected. The
prevalence is even higher in developing countries with up to 80% of them being affected.
Although some of the patients with H. pylori infection are asymptomatic, 10-20% of them may
progress into H. pylori associated disease such as chronic gastritis, peptic ulcer disease
and gastric malignancy. The clinical heterogeneity is believed to be due to different degree
of virulence across different H. pylori strains.
The American College of Gastroenterology (ACG) has outlined the standard therapies of H.
pylori infection, dividing them into first line and salvage therapy. Treatment regime is
chosen based on previous antibiotics exposure, antibiotics allergy and resistance.[7] The
eradication rate of 90% is regarded as successful in which, Kyoto Global Consensus Report
recommended the similar value as a cut-off point to guide the selection of empirical
treatment in each region. Clarithromycin triple therapy (clarithromycin,
amoxicillin/metronidazole and proton pump inhibitor, PPI) or referred as standard triple
therapy (STT) in our study is recommended as first line therapy for patients who are
macrolide-naive and/or reside in low clarithromycin-resistance area. For regions with high
clarithromycin resistance rate (more than 15%), ACG guideline recommends administration of
bismuth quadruple, non-bismuth quadruple or concomitant therapies.
The Maastricht V/Florence Consensus report has outlined the guidelines on diagnosis and
therapeutic strategies in H. pylori infection. The report highlighted failure of many
countries to hit at least 80% intention-to-treat eradication rate.[9] Amongst the
contributing factors are emerging antibiotics resistance, poor compliance, adverse effects of
antimicrobial regime leading to poor treatment adherence, high bacterial load and impairment
of gastric mucosal immunity.
Regionally, the Bangkok Consensus Report by Vilaichone et al in 2018 has studied the
prevalence of H. pylori infection in nine ASEAN countries. The study demonstrated high
prevalence of H. pylori in ASEAN countries ranging between 20% to 69%. Despite Malaysia
having the lowest H. pylori prevalence of 20%, the eradication rates failed to meet the
minimum 80% target when given STT for 7 days. Qua et al (2010) and Leow et al (2018) reported
the eradication rate of 71.2% and 79.3% respectively. Extending duration of STT from seven to
fourteen days illustrated marked improvement of eradication rate to 88.6% but it was still
below the successful eradication target of 90%.
In Malaysia, the rising primary resistance rate of H. pylori to antimicrobial agents mainly
clarithromycin poses a big challenge in treating this infection effectively. The earlier
studies by Teh at al (2014) demonstrated a primary resistance rate of 6.8% to both
clarithromycin and fluoroquinolones, 32.3% to metronidazole; Hanafiah et al (2019) reported a
primary resistance rate of 12.2%, 17.1% and 56.1% to clarithromycin, levofloxacin and
metronidazole respectively. The recent study by Puah et al (2021) illustrated a further
increment of clarithromycin resistance rate to 14.8%; whereas levofloxacin resistance rate
was 3.3%.
Looking at the increasing antibiotics resistance and suboptimal eradication rate in Malaysia,
further research to improve the overall efficacy of H. pylori eradication is undoubtedly
paramount. Over the years, probiotics have shown promising benefits in a vast spectrum of
gastrointestinal disorders including H. pylori infection. Several meta-analyses have
demonstrated significant reduction of H. pylori eradication rate in subjects receiving
probiotics as adjunct treatment. However, not all strains of probiotics are beneficial in
treating H. pylori as some of them are unable to survive in the gastric environment. The
Maastricht V/Florence Consensus Report emphasised that only certain probiotics are helpful in
H. pylori eradication, and that includes Lactobacillus, Bifidobacterium and Saccharomyces
boulardii. Amongst these, a single-strain Lactobacillus reuteri DSM 17648 has demonstrated
good outcome in improving eradication rate as well as ameliorating adverse effect of
treatment regime; both in human and in-vitro studies.
The probiotic used in the study was Pylobalance® which contains patented ingredient of
Lactobacillus reuteri DSM 17648. The co-aggregation of probiotic and H. pylori impairs
adhesion of bacterial pathogen to gastric mucosa and subsequently clears H. pylori from the
stomach. The ability of Lactobacillus reuteri to co-aggregate with H. pylori without
interfering with the original commensal microflora helps to preserve a stable gastric
microecology. This characteristic helps to reduce gastrointestinal symptoms associated with
H. pylori pathogen. The probiotic also has antimicrobial properties derived from short-chain
fatty acid from lactic acid, hydrogen peroxide and bactericidal substance of reuterin which
directly inhibit survival and proliferation of H. pylori. Regulation of immune response,
improvement of gut mucosal barrier and production of cell-surface protein to competitively
inhibit binding of H. pylori are amongst several other mechanism being proposed by previous
studies to ameliorate H. pylori pathogen effect. Another advantageous characteristic of
Lactobacillus reuteri is its ability to withstand unfavourable gastric environment owing to
its non-viable preparation form.
To our knowledge, the efficacy of Lactobacillus reuteri probiotic as the adjunct treatment in
H. pylori management has yet to be studied in Malaysian and South East Asian cohort. Owing to
the clinical heterogeneity of H. pylori strains across different or even in similar
population, the efficacy of Lactobacillus reuteri in our population needed to be investigated
further. In this study, we sought to determine the effect of Lactobacillus reuteri in H.
pylori eradication; mainly in improving eradication rate, ameliorating gastrointestinal
symptoms and reducing adverse effects of antibiotics.
