Clinical Evaluation of the Effects of EpiCor Brand Yeast Fermentate (Made Using Saccharomyces Cerevisiae) on Digestive Comfort, Intestinal Barrier Function and Prebiotic Modulation of the Gut Microbiota.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- ProDigest
- 入组人数
- 80
- 主要终点
- Symptoms of gastrointestinal discomfort
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Blinding was ensured by the fact that both capsules (placebo and EpiCor) were opaque and had an identical appearance and were packed in identical bottles by Embria Health Sciences and were labeled as A or B. A ProDigest staff member not participating in the study labelled all bottles and assigned them to each subject in accordance with the randomization list. All study participants, all members of ProDigest staff involved in the study and the Drug Research Unit Ghent (University Hospital Ghent) that actually performed the study, were blinded.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Based on medical history, healthy volunteers without clinical diagnosed diseases with relevant effect on gastrointestinal system or on visceral motility.
- •At the moment of initial inclusion subjects will be recruited for run-in phase if having reported:
- •Gastrointestinal (GI) symptoms of at least 5 points for the previous 3 months based on self-assessment, or
- •Reduced bowel movements defined as an average of >1 and ≤5 stools per week for the previous 3 months based on self assessment.
- •For at least 50 subjects, an additional inclusion criterion will have to be met based on the daily recorded GI symptoms: at the end of the run-in phase, a score of > or = 5 for GI symptoms should be obtained based on the average calculated from the daily scores of the 2-week run-in period. For the remaining 30 subjects, no additional inclusion criterion will be required.
- •Age > or = 18 and < or = 70 years.
- •Male or female.
- •No pregnancy in the last 6 months.
- •Body mass index (BMI) 18-35 kg/m2 (BMI = weight (kg) divided by length (m) squared).
- •Consistently stable body weight (± 5%) for at least 6 months and no weight reduction treatment during the study period.
- •Written consent to participate in the study.
- •Able and willing to follow the study protocol procedures
排除标准
- •History of severe gastrointestinal/hepatic, hematological/immunologic, metabolic/nutritional disorders, endocrine disorders, celiac disease, type I diabetes mellitus, major surgery and/or laboratory assessments which might limit participation in or completion of study period. Participants having other diseases will be considered or not for randomization after careful evaluation by the principle investigator.
- •Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to first dosing. Some medication may be used, if it is considered not to influence gastrointestinal function and motility, upon mutual agreement of the investigator and sponsor.
- •a. In particular, the use of any non-steroidal inflammatory drugs (NSAIDs) starting 14 days prior to first dosing is prohibited.
- •Systemic antibiotics treatment within 60 days prior to first dosing.
- •Intake of laxatives or anti-diarrheic drugs within 14 days prior to first dosing.
- •Change of dietary habits within the 4 weeks prior to screening (for instance start of a diet rich in fibers).
- •Participants anticipating a change in lifestyle or physical activity levels during the study.
- •Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 60 days prior to first dosing.
- •Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgment of the principle investigator).
- •Known pregnancy or lactation (checked by a pregnancy test before start of study).
- •Dependence on illegal drugs or alcohol.
- •Smoking within the last 3 months.
- •Blood donation within 1 month before study period.
- •Prohibited use of pro-, pre- or synbiotics from 30 days before first dosing and during the study period. A list with forbidden products will be provided.
- •Hepatitis C-, B- or HIV-positive (to be tested before start of study).
- •History of any major side effects towards intake of pro- or prebiotic supplements of any kind.
结局指标
主要结局
Symptoms of gastrointestinal discomfort
时间窗: Daily for 8 weeks
The volunteers will be asked to document daily (during the 2-week run-in phase and 6-week intervention phase) their Gastrointestinal (GI) symptoms. For assessment of GI symptoms, the volunteers will be asked to grade daily in the evening the average severity over the previous 24 hours on a 5-point scale from 0 (not at all) to 4 (extremely) for the following GI characteristics: bloating/distension, passage of gas, GI rumbling, feeling of fullness and abdominal discomfort. The run-in diary will also be used as an instrument to include/exclude volunteers from the study after proper assessment during the 2 week run-in phase (see additional inclusion criteria).
Stool frequency and consistency
时间窗: Daily for 8 weeks
The volunteers will be asked to document daily (during the 2-week run-in phase and 6-week intervention phase) their stool frequency and consistency. Stool consistency will be recorded by using the Bristol Stool Form Scale (watery or mushy, soft blobs, normal sausage, hard shaped sausage, hard lumps).
General gastrointestinal well-being
时间窗: 3 visits (V1=baseline, V2=3-weeks intervention, V3=6-weeks intervention)
General gastrointestinal well-being will also be evaluated by means of one additional questionnaire: the Patient Assessment of Constipation Symptoms (PAC-SYM) (Janssen Global Services, LLC, USA). This questionnaire was developed and validated in a patient population with history of chronic constipation. The PAC-SYM questionnaire is a 12-item self-reporting instrument divided into abdominal, rectal, and stool domains, which will be used to assess the constipation symptoms at the beginning (after 2-week run-in phase; visit 1), middle (after 3-weeks intervention; visit 2) and end of intervention (after 6-weeks intervention; visit 3) retrospectively. A 5-point scale from 0 (absent) to 4 (very severe) is used to assess the different symptoms.
Constipation-associated quality of life
时间窗: 3 visits (V1=baseline, V2=3-weeks intervention, V3=6-weeks intervention)
Constipation-associated quality of life will also be evaluated by means of one questionnaire: the Patient Assessment of Constipation Quality of Life (PAC-QOL) (Janssen Global Services, LLC, USA). This questionnaire was developed and validated in a patient population with history of chronic constipation. The PAC-QOL provides information about the special distraction of daily life and general well-being of volunteers because of constipation. The PAC-QOL questionnaire is a 28-item self-reporting instrument divided into four domains: physical discomfort, psychosocial discomfort, worries and concerns and satisfaction. This will be filled in by the participants at the same time as PAC-SYM: at the beginning (after 2-week run-in phase; visit 1), middle (after 3-weeks intervention; visit 2) and end of intervention (after 6-weeks intervention; visit 3) retrospectively. A 5-point scale from 0 (none of the time) to 4 (all of the time) is used to assess the different symptoms.
Perceived stress
时间窗: 3 visits (V1=baseline, V2=3-weeks intervention, V3=6-weeks intervention)
It is known that psychosocial factors, such as daily stress may alter gut physiology leading to ileum contractions and consequently to GI discomfort. Therefore, subjects will be asked to scale their stress levels in the Perceived Stress Scale (PSS) questionnaire. This is the most widely used psychological (and generic) instrument for measuring the perception of stress. This is a 10-item self-reporting. This will be filled in by the participants at the same time as PAC-SYM and PAC-QOL: at the beginning (after 2-week run-in phase; visit 1), middle (after 3-weeks intervention; visit 2) and end of intervention (after 6-weeks intervention; visit 3) retrospectively. A 5-point scale from 0 (never) to 4 (very often) is used to assess the different symptoms.
次要结局
- Intestinal barrier function: the Multi-Sugar Permeability Test(2 visits (V1=baseline, V3=6-weeks intervention))
- Intestinal barrier function: Zonulin and Endotoxin levels(2 visits (V1=baseline, V3=6-weeks intervention))
- Prebiotic properties: Gut microbiota analysis(3 visits (V1=baseline, V2=3-weeks intervention, V3=6-weeks intervention))
- Immune function(3 visits (V1=baseline, V2=3-weeks intervention, V3=6-weeks intervention))