Clinical Evaluation of the Effects of EpiCor on Digestive Comfort
Condition: Constipation; Gastrointestinal Discomfort
MeSH terms: Constipation
Study type: Interventional

Summary: 
      Previous in vitro studies suggest that EpiCor is well fermented in the colon and has
      prebiotic potential. The repeated long-term administration of low doses of EpiCor in the
      Simulator of the Human Intestinal Microbial Ecosystem (SHIME) has shown that this product is
      able to induce gradual changes in the colonic environment by: i) being selectively fermented,
      leading to butyrate increase in the colon; ii) stimulating Lactobacilli growth in the lumen
      and adherence to the mucosal surface, and iii) decreasing potential pathogens. In addition,
      the fermentation-derived metabolites produced in the colon were shown to potentially benefit
      the host by decreasing cytokine levels in vitro. As a result, the investigators hypothesize
      that EpiCor may help to improve bowel function and generally contribute to enhanced gut
      health. Therefore, this pilot study is intended to assess the effects of long-term
      administration of EpiCor on a population with mild symptoms of intestinal dysfunction.

      The primary objective of this exploratory pilot study is to assess the effect of long term
      administration of EpiCor on bowel function and gastrointestinal well-being, by means of
      validated questionnaires.

      This study has 4 secondary objectives: 1) The first secondary objective of this study is to
      assess the protective effects of EpiCor on intestinal barrier function, by performing a gut
      sugar permeability test in combination with indomethacin challenge; 2) The second secondary
      objective is to assess the effects of EpiCor on intestinal barrier function, by measuring
      blood Zonulin and endotoxin levels in combination with indomethacin challenge; 3) The third
      secondary objective of this study is to assess the prebiotic properties of EpiCor by
      collecting fecal samples. The microbial community composition, lactate and SCFA profiles and
      proteolytic activity markers in feces will be determined. Proteolytic activity markers will
      also be measured in urine samples; 4) The fourth secondary objective of this study is to
      assess the effects of EpiCor on local and systemic immune system performance by measuring
      secretory IgA levels in feces and cytokines in blood.
    

Detailed description: 
      Study design:

      In this project the effects of repeated daily intake of EpiCor will be investigated. The
      design conforms to a randomized, double-blind, placebo-controlled parallel design. In total,
      there will be two study groups: one group receiving placebo treatment (maltodextrin 500mg
      daily dose, single serving) and one group receiving EpiCor (500mg daily dose, single
      serving). Each eligible individual will participate in one of two experimental arms of the
      study for minimum 6 weeks. Before randomization, there will be a run-in period of 2 weeks in
      which the participants are prohibited from consuming products containing pre- or probiotics.

      Study population:

      Healthy human male/female volunteers with mild symptoms of intestinal dysfunction. Subject
      recruitment will start after ethics committee approval of the study. After obtaining signed
      informed consent and confirmation of eligibility, each subject will have 4 test days at the
      study site. Each subject will participate during approximately 8 to 10 weeks in this study.
      In total, 80 subjects will complete the study (40 subjects in each trial arm). For any
      patient withdrawn from the study, an alternative candidate will be selected in order to
      ultimately meet the required number of subjects. The total study duration will be
      approximately 20 weeks.

      Study endpoints:

      The primary endpoint for this study is the effect of long-term administration of EpiCor on
      digestive comfort. Digestive comfort will be assessed by means of evaluation (questionnaires)
      of i) Gastrointestinal (GI) symptoms (bloating/distension; passage of gas; GI rumbling;
      feeling of fullness and abdominal discomfort) and ii) frequency/consistency of stools.
      General gastrointestinal well-being and improvement of quality of life will also be evaluated
      by means of questionnaires.

      Secondary endpoints are i) the protective effects of EpiCor on gut barrier function after
      indomethacin challenge (assessed by a sugar test in urine samples), ii) the effects of EpiCor
      on gut barrier function after indomethacin challenge (assessed by quantification of Zonulin
      in blood), iii) evaluation of EpiCor's prebiotic properties (assessed by microbiota-related
      analyses on fecal contents) and iv) the effect of EpiCor on local and systemic immune system
      performance (assessed by measuring secretory (s)IgA levels in feces and cytokines in blood).

      Study product:

      EpiCor (Embria Health Sciences) is the brand name for a substance consisting of a dried yeast
      fermentate made using Saccharomyces cerevisiae fermentation. All published human studies on
      EpiCor used a daily dosage of 500mg for adults. Moreover, this is the commercially
      recommended daily dosage, and will also be used in this study. The placebo used in this study
      is Globe maltodextrin 10 (CPIngredientes, Mexico). This commercially available product is a
      mixture of dextrose, maltose, oligo and polysaccharides obtained by partial enzymatic
      hydrolysis of corn starch. Maltodextrin is the most commonly used placebo in dietary studies
      evaluating gut microbiota and intestinal well-being. It is easily digestible and rapidly
      absorbed as glucose and has no effect on colonic fermentation.

      EpiCor and placebo will be provided in capsules. The capsules used in this study will be the
      Coni-Snap® capsules, two-piece hard gelatin capsules (Capsugel, Mexico).

      Blinding procedures:

      Blinding is ensured by the fact that both capsules are opaque and have an identical
      appearance and are packaged in identical bottles by Embria Health Sciences. A ProDigest staff
      member not participating in the study will label all bottles and assign them to each subject
      in accordance to the randomization list. The capsules will be packed in identical bottles.
      Each bottle will contain a weekly dose (=7 capsules per bottle).

      The participants will be asked to orally ingest one capsule per day, in combination with
      200mL water. The capsules will consist of 500mg EpiCor® or 500mg maltodextrin. To ensure a
      standardized intake, participants will be asked to take the capsule every morning before
      breakfast. No interactions with food are reported, and so participants may proceed with their
      usual food habits. Participants will be asked to hand in the empty bottles; these will be
      used to measure compliance.

      The products are to be stored at room temperature in dry conditions in the closed bottles
      (preferably between 15 and 25 °C) for the duration of the study.
    

Intervention name(s): Placebo; EpiCor
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The participants will be asked to orally ingest one capsule per day (500 mg maltodextrin, single serving), in combination with 200mL water.; The participants will be asked to orally ingest one capsule per day (500 mg EpiCor, single serving), in combination with 200mL water.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Pilot study performed according to a randomized, double-blind, placebo-controlled parallel design
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Constipation; Gastrointestinal symptoms of discomfort; Quality of life; Saccharomyces cerevisiae; Gut microbiome