A Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome

Study Overview
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Brief Summary
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This is a prospective, randomized, placebo-controlled, double-blind, multi-center parallel- design study to evaluate the effect of BL NCC3001 in subjects with Irritable Bowel Syndrome.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome

Conditions
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IBS - Irritable Bowel Syndrome

Intervention / Treatment
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* Dietary Supplement: Bifidobacterium longum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age between 18 and 70 years inclusive. Willing and able to sign written informed consent prior to study entry. Able to comply with the study procedures, in the opinion of the investigator. Subjects diagnosed with IBS. All subtypes based on Rome IV Criteria with active IBS symptoms as indicated by a score of ≥ 125 on the IBS-SSS. Subjects with psychological symptoms in the absence of a psychiatric diagnosis, defined as a score of 5 to 13 in the depression domain and/or a score of 4 to 9 in the anxiety domain of the DASS-21 questionnaire. Exclusion Criteria: Concurrent formal diagnosis by a psychiatric specialist, including any mood or anxiety disorder, according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders 4th or 5th edition. Concurrent systemic disease and/ or laboratory abnormalities considered by the investigator to be clinically relevant or that could interfere with data collection or interpretation. Concurrent organic gastrointestinal pathology other than benign polyps, diverticulosis, hemorrhoids, lipomas, and melanosis coli. History of attempted suicide in the past 5 years. Previous abdominal surgery except for hernia repair, appendectomy, caesarian section, tubal ligation, hysterectomy, and hemorrhoidectomy. History of substance abuse in the past 2 years, including opiates, phencyclidine, benzodiazepines, amphetamines, cocaine, heroin, alcohol, and cannabinoids (except if medically indicated). Subjects who are on daily treatment with therapeutic doses of drugs having central nervous system effects, including antidepressants and/ or anxiolytics. Low doses of (I) tricyclic antidepressants for abdominal pain/diarrhea related to IBS and (II) anxiolytics used as sleeping pills will be permitted if dose is stable > 3 months prior to the date of randomization. Pregnant or breastfeeding women. Subjects with dementia or other cognitive impairment. Subjects who received antibiotics within the 4 weeks prior to the date of randomization . Known or suspected allergies to the study products. Subjects with increased risk of probiotic sepsis as the following conditions: Immune compromise, including debilitating state or malignancy, central venous catheter, impaired intestinal epithelial barrier (acute diarrheal illness, intestinal inflammation, etc.), cardiac valvular disease. Subjects currently participating or having participated in a therapeutic trial within 3 months prior to the date of randomization. Medically diagnosed lactose intolerance and fructose intolerance without being on a stable lactose or fructose free diet (> 3 months prior to the date of randomization). Medically diagnosed celiac disease. Consumption of any probiotic supplements specified as containing Lactobacillus, Bifidobacteria, Streptococcus, Bacillus coagulans, and Saccharomyces at least 2 weeks prior to the date of randomization. Subjects on regular use of drugs to control IBS symptoms such as bile acid binders (cholestyramine, colestipol or colesevelam, rifaximin, alosetron, lubiprostone, eluxadoline and linaclotide). Recently initiated exclusion diets. Subjects on stable exclusion diets (> 3 months prior to the date of randomization) will not be excluded. This includes subjects with the following diets: gluten-free, lactose-free, paleo, vegetarian, vegan, and low-carbohydrate. Low-FODMAP diet. Subjects on the induction phase of the FODMAP exclusion will not be enrolled. Subjects on the maintenance phase of the diet for more than 3 months prior to the date of randomization with stable diet can be considered for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic<br>Bifidobacterium longum [BL NCC3001] | Dietary Supplement: Bifidobacterium longum<br>* A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome<br>|
| Placebo Comparator: Placebo<br>Maltodextrin | Dietary Supplement: Bifidobacterium longum<br>* A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effects of Bifidobacterium Longum NCC3001 on Intestinal and Psychological Symptoms in Subjects With Irritable Bowel Syndrome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of Bifidobacterium Longum (BL NCC3001) on Gastrointestinal Symptoms | Change from baseline to week 6 in Irritable Bowel Severity Scoring System (IBS-SSS), a questionnaire that includes 5 questions related to the severity of abdominal pain, frequency of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits, and interference with quality of life over the past 10 days. This cumulative score can therefore range from 0 to 500, with higher scores indicating more severe symptoms. | Baseline to 6 weeks. | 
| To evaluate the effect of Bifidobacterium Longum (BL NCC3001) on Psychological Symptoms | Change from baseline to week 6 in Hospital Anxiety and Depression Scale (HADS-Total) score, a 14-item scale assessing two dimensions (anxiety and depression, 7 items for each) of psychological distress. Each item is scored from 0-3 in a Likert manner. Outcome measures are the anxiety score (0-21), depression score (0-21) and the total score (0-42). | Baseline to 6 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Anxiety Depression Scale - Depression (HADS-D) score | Change from baseline to Week 6 in Hospital Anxiety Depression Scale-Depression (HADS-D) score, a 14-item scale assessing depression (7 items) of psychological distress. Each item is scored from 0-3 in a Likert manner. Outcome measures are the depression score (0-21). | Day -1, Day 43 (± 2 days) | 
| Hospital Anxiety Depression Scale - Anxiety (HADS-A) score | Change from baseline to Week 6 in Hospital Anxiety Depression Scale-Anxiety (HADS-A) score, a 14-item scale assessing anxiety (7 items) of psychological distress. Each item is scored from 0-3 in a Likert manner. Outcome measures are the anxiety score (0-21). | Day -1, Day 43 (± 2 days) | 
| Depression Anxiety Stress Scale (DASS-21) | Change from baseline to Week 6 in Depression Anxiety Stress Scale (DASS-21), a four-point Likert scale ranging from 0 (did not apply to me at all) to 3 (applied to me very much or most of the time). The outcome measures correspond to the total scores (0-21) of the subscales. | Day -1, Day 43 (± 2 days) | 
| Perceived Stress Scale (PSS) | Change from baseline to Week 6 in Perceived Stress Scale (PSS), includes several direct queries about current levels of experienced stress, each item is rated on a Likert scale (0-4), the range of the total score is 0-40. | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Severity Scoring System (IBS-SSS) Pain severity | Change from baseline to Week 6 in Irritable Bowel Severity Scoring System (IBS-SSS) pain severity, a question related to the severity of abdominal pain over the past 10 days. The question is scored on a 100-point visual analogue scale, which is anchored with the 2 extremes (e.g., no pain on the far left to severe pain on the far right). | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Severity Scoring System (IBS-SSS) Pain frequency | Change from baseline to Week 6 in Irritable Bowel Severity Scoring System (IBS-SSS) pain frequency, a question related to the frequency of abdominal pain over the past 10 days. The question is scored on a 100-point visual analogue scale, which is anchored with the 2 extremes (e.g., no pain on the far left to severe pain on the far right). | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Severity Scoring System (IBS-SSS) Bloating severity | Change from baseline to Week 6 in Irritable Bowel Severity Scoring System (IBS-SSS) bloating severity, a question related to the severity of abdominal distention over the past 10 days. The question is scored on a 100-point visual analogue scale, which is anchored with the 2 extremes (e.g., no pain on the far left to severe pain on the far right). | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Severity Scoring System (IBS-SSS) Bowel habit | Change from baseline to Week 6 in Irritable Bowel Severity Scoring System (IBS-SSS) bowel habit, a question related to dissatisfaction with bowel habits over the past 10 days. The question is scored on a 100-point visual analogue scale, which is anchored with the 2 extremes (e.g., no pain on the far left to severe pain on the far right). | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Severity Scoring System (IBS-SSS) Life impact | Change from baseline to Week 6 in Irritable Bowel Severity Scoring System (IBS-SSS) life impact, a question related to interference with quality of life over the past 10 days. The question is scored on a 100-point visual analogue scale, which is anchored with the 2 extremes (e.g., no pain on the far left to severe pain on the far right). | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Syndrome Quality of Life questionnaire (IBS-QoL) | Change from baseline to Week 6 in Irritable Bowel Syndrome Quality of Life questionnaire (IBS-QoL), a 34-item, validated, condition-specific measure based on 5-point Likert scale for assessing health-related quality of life in the past month among persons with IBS. | Day -1, Day 43 (± 2 days) | 
| Patient Health Questionnaire (PHQ-12) | Change from baseline to Week 6 in Patient Health Questionnaire (PHQ-12), each somatic symptom is evaluated in a Likert scale from 0 to 2 (not bothered at all, bothered a little and bothered a lot) giving a maximum total of 24 points. | Day -1, Day 43 (± 2 days) | 
| Sheehan Disability Scale (SDS) | Change from baseline to Week 6 in Sheehan Disability Scale (SDS), the patients rates the extent to which work/school, social and family life are impaired by his/her symptoms on a 10-point VAS. | Day -1, Day 43 (± 2 days) | 
| Amount of Bifidobacterium Longum (BL NCC3001) present in stool | Change from baseline to Week 6 | Day -1, Day 43 (± 2 days) | 
| Irritable Bowel Severity Scoring System (IBS-SSS) score | Change from baseline to Week 10 in Irritable Bowel Severity Scoring System (IBS-SSS) score, a cumulative score which can therefore range from 0 to 500, with higher scores indicating more severe symptoms. Mild, moderate, and severe cases are indicated by scores of 75 to 175. | Day -1, Day 71 (± 2 days) | 
| Hospital Anxiety Depression Scale (HADS) total score | Change from baseline to Week 10 in Hospital Anxiety Depression Scale (HADS) total score, a 14-item scale assessing two dimensions (anxiety and depression, 7 items for each) of psychological distress. Each item is scored from 0-3 in a Likert manner. Outcome measures are the anxiety score (0-21), depression score (0-21) and the total score (0-42). | Day -1, Day 71 (± 2 days) | 
| Rescue Medication | Difference in proportions compared to placebo at Week 6 | Day 43 (± 2 days) | 
| Psychological distress improvement according to the Patient's Global Impression of Change of Psychological Distress | Difference in proportions compared to placebo at Week 6 using a 7-point Likert scale depicting a patient's rating of overall improvement of the psychological distress since the beginning of treatment. The range of the score is 1 to 7. | Day 43 (± 2 days) | 
| Active treatment randomization perception: Do you think you have taken the placebo or active treatment? | Difference in proportions compared to placebo at Week 6 | Day 43 (± 2 days) |