Study of Pylopass Versus Placebo in Subjects Who Are Helicobacter Pylori Carriers and With Mild Indigestion
Condition: HELICOBACTER INFECTION
MeSH terms: Helicobacter Infections; Dyspepsia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Helicobator pylori (H. pylori) is a bacteria which survives in the lining of the stomach. An
      estimated 50% of the world's population is infected with H. pylori. Developing economies,
      such as in Southeast Asia, the Indian subcontinent and Latin America, have prevalence rates
      of as high as 90%.

      H. pylori infection often goes undiagnosed, as many sufferers do not experience any adverse
      symptoms. Infection with H. pylori is described as "not a disease in itself but a condition
      that affects the relative risk of developing various clinical disorders of the upper
      gastrointestinal tract.' Clinically relevant symptoms could include peptic ulcer, melena or
      secondary conditions such as iron deficiency anemia or vitamin B12 deficiency.

      There is evidence that probiotics can be beneficial for those with gastrointestinal diseases.
      Pylopass contains the probiotic strain Lactobacillus reuteri, which was selected for its
      anti-H. pylori characteristics and in clinical trials has shown to result in a reduction in
      urease breath test values in subjects with H. pylori.

      The objective of this study is to evaluate the ability of Pylopass to reduce H. pylori load
      in subjects who are H. pylori positive.
    

Detailed description: 
      Helicobator pylori (H. pylori) is a gram negative, spiral shaped bacteria which colonizes in
      the gastric mucosa. An estimated 50 percent of the world's population is infected with H.
      pylori.

      H. pylori infection does not necessarily result in clinically relevant symptoms. Ching and
      Wong report that most cases of H. pylori are asymptomatic . Moreover, Kusters et al states
      that infection with H. pylori "is not a disease in itself but a condition that affects the
      relative risk of developing various clinical disorders of the upper gastrointestinal tract"
      (Kusters, 2006). Clinically relevant symptoms could include peptic ulcer, melena or secondary
      conditions such as iron deficiency anemia or vitamin B12 deficiency.

      The most recent iteration of the Maastricht/Florence Consensus report outlines the diagnostic
      guidelines and treatment strategies for those with H. pylori (Malfertheiner 2012).
      Individuals with certain risk factors, such as a family history of gastric cancer, bleeding
      ulcer or with secondary disease such as iron deficiency anemia should undergo eradication
      therapy. For those with functional dyspepsia, the test and treat strategy has been
      recommended. However, there remains a lack of options for volunteers who are either
      asymptomatic or experience mild gastrointestinal symptoms who are not indicated for
      eradication therapy or to undergo the test and treat strategy.

      There is evidence that probiotics can be beneficial for those with gastrointestinal diseases.
      A review by Ritchie and Romanuk succinctly summarizes this point by writing that "probiotics
      are generally beneficial in treatment and prevention of gastrointestinal diseases" (Ritchie
      2012). In the context of H. pylori infection, probiotics are administered alongside
      conventional eradication treatment regimens to lessen the severity of side effects and
      improve tolerance. Francavilla et al has studied the impact of Lactobacillus reuteri on H.
      pylori load levels, as measured by urea breath test (UBT) values. The researchers found that
      a significant reduction in H. pylori load as evidenced by significantly decreased UBT values.
      They also found a decrease in symptom scores as measured by the Gastrointestinal Symptom
      Rating Scale (GSRS) (Francavilla 2008). Imase et al has also studied the impact of
      Lactobacillus reuteri supplementation in H. pylori infected individuals and found a
      suppressive effect from the L. reuteri tablets on UBT values (Imase 2007). These studies
      indicate that Lactobacillus reuteri exerts an effect on H. pylori by lowering the load.

      There are many potential mechanisms by which probiotic strains, such as Lactobacillus
      reuteri, could exert a suppressive effect against H. pylori. One potential method is to
      stabilize or strengthen the gut mucosal barrier. Other mechanisms include sequestration of H.
      pylori, production of antimicrobial substances or through competitive binding to receptors in
      the gut (Garcia, 2009; Lesbros-Pantoflickova, 2007).

      The Pylopass strain of Lactobacillus reuteri (L. reuteri) was identified after a detailed,
      multi-year screening process. It was selected for its anti-H. pylori characteristics from a
      culture collection of 8,000 different food grade strains. The original commensal environment
      of the Pylopass strain of L. reuteri is from humans. L. reuteri is considered one of the few
      autochthonous lactobacilli in humans and animals known to the scientific community. It has
      been isolated in the gastrointestinal tract of humans, pigs, cattle and dogs (Casas 2000). It
      has also been isolated in a variety of different foods, such as milk products and fermented
      rice noodles.

      Pylopass is comprised of Lactobacillus reuteri cells, suspended in a matrix and spray dried.
      As such, the Lactobacillus reuteri cells are metabolically inactive. However, through in
      vitro and human studies, it has been shown to exert an H. pylori load lowering effect. In
      vitro work has found that Pylopass specifically coaggregates with H. pylori under acidic
      conditions. Two human pilot studies have shown that oral administration of Pylopass leads to
      a reduction in UBT values in volunteers with H. pylori (Mehling 2013). As the cells of the
      Lactobacillus reuteri in Pylopass do not need to be metabolically active to exert a benefical
      effect, this provides tremendous advantages in developing economies, where there are many
      cases of antibiotic resistant H. pylori.

      The advantages of Pylopass over other Lactobacillus products are product stability,
      specificity for H. pylori and stability in gastric conditions. As previously mentioned, the
      highest prevalence of H. pylori is in developing economies, where access to an adequate cold
      chain may not be reliable. As Pylopass is comprised of inactivated cells which can withstand
      environmental fluctuations, it is appropriate for shipments that do not require temperature
      control. Secondly, while probiotics cater to general gut health, Pylopass specifically bind
      H. pylori under acidic conditions. Thirdly, the mechanism of action is not dependent on
      binding sites or survival in the gastric environment. Probiotics can be beneficial because
      they may replace harmful bacteria in the gastrointestinal tract. However, it is uncertain
      whether such living strains can withstand the acidic environment in the stomach. This concern
      is not a challenge for Pylopass as the coaggregation depends only on the binding of surface
      structures between Pylopass and H. pylori. As there are advantages to Pylopass over
      traditional probiotic strains, it is the goal of this study to confirm that the results from
      the first two human trials hold true.

      Given the challenges of rising rates of antibiotic resistance, delivery of a product which is
      relevant and useful in developing economies, development of a product which can withstand
      environmental fluctuations and the lack of options for H. pylori positive individuals who are
      not indicated for eradication therapy, the development of Pylopass could be an important tool
      to address these challenges. To this end, the goal of this study is to assess the impact of a
      four week supplementation period of Pylopass on markers of Helicobacter pylori load in
      volunteers who do not meet the full criteria for eradication therapy as outlined by the
      Maastricht Florence Consensus report.

      The primary outcome of this study is the urease breath test (UBT), a widely validated
      non-invasive measure for H. pylori status. However, we also recognize that there are
      limitations of using the urease breath test. The primary limitation is that the UBT serves as
      a proxy measure for Helicobacter pylori load levels and does not provide direct assessments
      of the health of the gastric mucosa or of H. pylori load. By including a subset of volunteers
      for gastric biopsies, the degree of inflammation can be directly assessed and the H pylori
      load can be quantified. By performing biopsies at two time points, before and after
      supplementation with the active ingredient, the effects of the supplement on the health of
      the gastric mucosa can be assessed. Due to the small subset of volunteers, the information
      will be qualitative in nature, but will provide a scientific basis for assessing participants
      in future studies. As antibiotic resistance is on the rise in cases of Helicobacter pylori,
      it is important to continuously develop new adjunctive solutions which may help improve the
      health of the gastric mucosa, and the best way to assess this directly is through the use of
      gastric biopsies.
    

Intervention name(s): Pylopass; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): Pylopass; Placebo
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Helicobacter pylori; Mild Indigestion