A Study to Investigate the Safety and Efficacy of a Probiotic on Gastrointestinal Health in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
Eligible participants will be randomized and receive either the probioic or placebo supplement to consume daily for 28-days. Three check-in visits will occur every 7 days of study participation. Participants will be expected to complete a daily study diary documenting their investigational product use/adverse events and a daily bowel habits diary documenting each bowel movement. Blood samples, stool samples, and questionnaires will be completed for study outcome analysis.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Parallel, Research Study to Investigate the Safety and Efficacy of a Probiotic Lactobacillus Plantarum 276 (Lp276) on Gastrointestinal Health in Healthy Adults

Conditions
-----------------
Gastrointestinal Health, Healthy

Intervention / Treatment
-----------------
* Dietary Supplement: Lactobacillus plantarum 276
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females and males between 18 to 55 years of age, inclusive BMI between 18.5 to 32 kg/m2, inclusive Self-reported history of diarrhea over the last 3 months, defined as > 5 BMs with the majority (≥ 50%) of the BMs per week being Bristol stool form types ≥5, 6 or 7 Female participant is not of child bearing potential, which is defined as females who have had a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation, or are post-menopausal (natural or surgically with > 1 year since last menstruation) OR, Females of childbearing potential must agree to use a medically approved method of birth control and must have negative urine pregnancy test results at screening and baseline. A minimum of 3-months stable dose is required for females on a hormonal birth control. Acceptable methods of birth control include: I. Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System) II. Double-barrier method III. Intrauterine devices IV. Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s) V. Vasectomy of partner (shown successful as per appropriate follow-up) Healthy as determined by laboratory results, medical history and physical exam by QI Agrees to comply with all study procedures Agrees to refrain from the use of any home remedies to control GI issues if live bacteria may be involved Agrees to avoid NSAIDs and Steroids for 72 hours and Vitamin C and related supplements for 24 hours prior to fecal zonulin sample collection Agrees to maintain current level of physical activity and diet throughout the study Agrees to provide written informed consent Exclusion Criteria: Women who are pregnant, breast feeding, or planning to become pregnant during the trial Allergy or sensitivity to investigational product's active or inactive ingredients Clinically significant abnormal laboratory results at screening as assessed by QI Chronic use of anti-diarrhea medications and supplements; occasional use is permitted based on frequency of use and appropriate wash-out to be determined by QI Currently undergoing pharmacological treatment for IBS, or history of active treatment for IBS within the last 1 year Clinically significant disease of the gastrointestinal tract (examples include but are not limited to celiac disease, gluten intolerance/sensitivity, inflammatory bowel disease) Gastrointestinal surgery within the past 3 months. Gastrointestinal surgery > 3 months ago, will be assessed by the QI on a case-by-case basis. Major surgery in the past 3 months or individuals who have planned surgery during the course of the trial. Minor surgery will be considered on a case by case basis by QI Cancer, except skin cancers completely excised with no chemotherapy or radiation with a follow up that is negative. Cancer in full remission for more than five years after diagnosis are acceptable. Verbal confirmation of autoimmune disease or if immune-compromised Verbal confirmation of HIV, hepatitis B/C positive diagnosis Metabolic syndrome or chronic diseases to be assessed by QI on a case by case basis Type I or Type II diabetes Significant cardiovascular event in the past 6 months. No significant cardiovascular event on stable medication may be included after assessment by the QI on a case by case basis History or currently with kidney and liver diseases assessed by QI on a case by case basis, with the exception of the history of kidney stones symptom-free for 1 year Verbal confirmation of current or pre-existing thyroid condition. Treatment on a stable dose medication for over 6 months will be reviewed on a case-by-case basis by the QI Blood or bleeding disorders, with the exception of a history of anemia caused by deficiency of a mineral or vitamin, and no longer present Current use or consumption of antibiotics in the 4 weeks prior to baseline Current use or consumption of prebiotic or probiotic or synbiotic supplements in the 4 weeks prior to baseline Current use of prescribed medications that may affect the study outcomes Use of over-the-counter (OTC) medications or supplements or consumption of foods/drinks that may affect the study outcomes, unless willing to undergo an appropriate washout period prior to baseline is agreed upon after assessment by the QI Use of medical marijuana Chronic use of recreational marijuana; infrequent use (>30 days since last use) to be assessed by QI Use of tobacco products unless quit 90 days prior to baseline Alcohol or drug abuse in the past year High alcohol intake (average of >2 standard drinks per day or >10 standard drinks per week) Use of narcotics Illicit drug use in the past 6 months as assessed by the QI Participation in other clinical research trials 30 days prior to randomization or will be participating in another investigation during the study Participants who plan to donate blood during the study or within 30 days of completing the study Any known (choric or acute) medical or neuropsychological condition that, in the QI's opinion, could interfere with study participation, or individuals who are cognitively impaired and/or who are unable to give informed consent Any other active or unstable medical condition, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose a significant risk to the participant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br> | Dietary Supplement: Lactobacillus plantarum 276<br>* 5 Billion CFU/dose, serving size = 1 capsule/day<br>* Other names: Lp276;|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo product, serving size = 1 capsule/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference between probiotic and placebo groups in the change in gastrointestinal health from baseline to day 28 as determined by stool frequency as per daily bowel habit diary | Number of bowel movements per day will be assessed in the bowel habits diary | 28 days | 
| The difference between probiotic and placebo groups in the change in gastrointestinal health from baseline to day 28 as determined by stool consistency as per the Bristol Stool Scale | Bristol Stool Scale is a seven-stool description and image scale within the Daily Bowel Habit Diary to assess stool shape and consistency (1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = like a sausage but with cracks on its surface, 4 = like a sausage or snake, smooth and soft, 5 = soft blobs with clear-cut edges, 6 = fluffy pieces with ragged edges/mushy stool, 7 = watery, no solid pieces). | 28 days | 
| The difference between probiotic and placebo groups in the change in gastrointestinal health from baseline to day 28 as determined by gastrointestinal (GI) symptoms as per the gastrointestinal symptom rating scale | The GSRS is a validated, self-assessed, disease-specific scale that will be administered at all in-clinic visits. Five symptom clusters depicted as Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation will be assessed from the combination of the 15 items in the questionnaire (Abdominal pains, Heartburn, Acid regurgitation, Sucking sensations in the epigastrium, Nausea and vomiting, Borborygmus, Abdominal distension, Eructation, Increased flatus, Decreased passage of stools, Increased passage of stools, Loose stools, Hard Stools, Urgent need for defecation, Feeling of incomplete evacuation). All the domains will be scored on a 3-point scale where 1 represented no symptoms and 3 represented severe symptoms | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 7 as determined by stool frequency as per the daily bowel habits diary | Number of bowel movements per day will be assessed in the bowel habits diary | 7 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 14 as determined by stool frequency as per the daily bowel habits diary | Number of bowel movements per day will be assessed in the bowel habits diary | 14 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 21 as determined by stool frequency as per the daily bowel habits diary | Number of bowel movements per day will be assessed in the bowel habits diary | 21 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 7 as determined by stool consistency as per the Bristol Stool Scale | Bristol Stool Scale is a seven-stool description and image scale within the Daily Bowel Habit Diary to assess stool shape and consistency (1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = like a sausage but with cracks on its surface, 4 = like a sausage or snake, smooth and soft, 5 = soft blobs with clear-cut edges, 6 = fluffy pieces with ragged edges/mushy stool, 7 = watery, no solid pieces). | 7 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 14 as determined by stool consistency as per the Bristol Stool Scale | Bristol Stool Scale is a seven-stool description and image scale within the Daily Bowel Habit Diary to assess stool shape and consistency (1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = like a sausage but with cracks on its surface, 4 = like a sausage or snake, smooth and soft, 5 = soft blobs with clear-cut edges, 6 = fluffy pieces with ragged edges/mushy stool, 7 = watery, no solid pieces). | 14 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 21 as determined by stool consistency as per the Bristol Stool Scale | Bristol Stool Scale is a seven-stool description and image scale within the Daily Bowel Habit Diary to assess stool shape and consistency (1 = separate hard lumps, 2 = sausage shaped but lumpy, 3 = like a sausage but with cracks on its surface, 4 = like a sausage or snake, smooth and soft, 5 = soft blobs with clear-cut edges, 6 = fluffy pieces with ragged edges/mushy stool, 7 = watery, no solid pieces). | 21 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 7 as determined by gastrointestinal symptoms as per the Gastrointestinal Symptom Rating Scale | The GSRS is a validated, self-assessed, disease-specific scale that will be administered at all in-clinic visits. Five symptom clusters depicted as Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation will be assessed from the combination of the 15 items in the questionnaire (Abdominal pains, Heartburn, Acid regurgitation, Sucking sensations in the epigastrium, Nausea and vomiting, Borborygmus, Abdominal distension, Eructation, Increased flatus, Decreased passage of stools, Increased passage of stools, Loose stools, Hard Stools, Urgent need for defecation, Feeling of incomplete evacuation). All the domains will be scored on a 3-point scale where 1 represented no symptoms and 3 represented severe symptoms | 7 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 14 as determined by gastrointestinal symptoms as per the Gastrointestinal Symptom Rating Scale | The GSRS is a validated, self-assessed, disease-specific scale that will be administered at all in-clinic visits. Five symptom clusters depicted as Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation will be assessed from the combination of the 15 items in the questionnaire (Abdominal pains, Heartburn, Acid regurgitation, Sucking sensations in the epigastrium, Nausea and vomiting, Borborygmus, Abdominal distension, Eructation, Increased flatus, Decreased passage of stools, Increased passage of stools, Loose stools, Hard Stools, Urgent need for defecation, Feeling of incomplete evacuation). All the domains will be scored on a 3-point scale where 1 represented no symptoms and 3 represented severe symptoms | 14 days | 
| The difference between probiotic and placebo groups in gastrointestinal health from baseline to day 21 as determined by gastrointestinal symptoms as per the Gastrointestinal Symptom Rating Scale | The GSRS is a validated, self-assessed, disease-specific scale that will be administered at all in-clinic visits. Five symptom clusters depicted as Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation will be assessed from the combination of the 15 items in the questionnaire (Abdominal pains, Heartburn, Acid regurgitation, Sucking sensations in the epigastrium, Nausea and vomiting, Borborygmus, Abdominal distension, Eructation, Increased flatus, Decreased passage of stools, Increased passage of stools, Loose stools, Hard Stools, Urgent need for defecation, Feeling of incomplete evacuation). All the domains will be scored on a 3-point scale where 1 represented no symptoms and 3 represented severe symptoms | 21 days | 
| The change in fecal zonulin levels from baseline to day 7 | Zonulin levels will be analysed from stool samples. A decrease in zonulin levels are associated with better intestinal health. | 7 days | 
| The change in fecal zonulin levels from baseline to day 14 | Zonulin levels will be analysed from stool samples. A decrease in zonulin levels are associated with better intestinal health. | 14 days | 
| The change in fecal zonulin levels from baseline to day 21 | Zonulin levels will be analysed from stool samples. A decrease in zonulin levels are associated with better intestinal health. | 21 days | 
| The change in fecal zonulin levels from baseline to day 28 | Zonulin levels will be analysed from stool samples. A decrease in zonulin levels are associated with better intestinal health. | 28 days | 
| The change in fecal calprotectin levels from baseline to day 28 | Calprotectin levels will be analysed from stool samples. A decrease in calprotectin levels are associated with better intestinal health. | 28 days | 
| The change in probiotic impact questionaire from baseline to day 14 | This 22-item questionnaire was specifically designed capture the impact of Lactobacillus plantarum 276 (Lp276) on participants health | 14 days | 
| The change in probiotic impact questionaire from baseline to day 28 | This 22-item questionnaire was specifically designed capture the impact of Lactobacillus plantarum 276 (Lp276) on participants health | 28 days | 
| The change in fecal microbial composition from baseline to day 7 | Microbial composition will be analysed from stool samples | 7 days | 
| The change in fecal microbial composition from baseline to day 14 | Microbial composition will be analysed from stool samples | 14 days | 
| The change in fecal microbial composition from baseline to day 21 | Microbial composition will be analysed from stool samples | 21 days | 
| The change in fecal microbial composition from baseline to day 28 | Microbial composition will be analysed from stool samples | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Probiotics, Healthy, Gut Health, Gastrointestinal Health