IBS - Irritable Bowel Syndrome
Conditions
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTBifidobacterium longum
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
Sponsors
Syneos Health
Medidata Solutions
McMaster University
CaligorRx, Inc.
Société des Produits Nestlé (SPN)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, age between 18 and 70 years inclusive. 2. Willing and able to sign written informed consent prior to study entry. 3. Able to comply with the study procedures, in the opinion of the investigator. 4. 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. 5. 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
1. 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. 2. Concurrent systemic disease and/ or laboratory abnormalities considered by the investigator to be clinically relevant or that could interfere with data collection or interpretation. 3. Concurrent organic gastrointestinal pathology other than benign polyps, diverticulosis, hemorrhoids, lipomas, and melanosis coli. 4. History of attempted suicide in the past 5 years. 5. Previous abdominal surgery except for hernia repair, appendectomy, caesarian section, tubal ligation, hysterectomy, and hemorrhoidectomy. 6. History of substance abuse in the past 2 years, including opiates, phencyclidine, benzodiazepines, amphetamines, cocaine, heroin, alcohol, and cannabinoids (except if medically indicated). 7. 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. 8. Pregnant or breastfeeding women. 9. Subjects with dementia or other cognitive impairment. 10. Subjects who received antibiotics within the 4 weeks prior to the date of randomization . 11. Known or suspected allergies to the study products. 12. 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. 13. Subjects currently participating or having participated in a therapeutic trial within 3 months prior to the date of randomization. 14. 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). 15. Medically diagnosed celiac disease. 16. 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. 17. 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). 18. 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. 19. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the effect of Bifidobacterium Longum (BL NCC3001) on Gastrointestinal Symptoms | Baseline to 6 weeks. | 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. |
| To evaluate the effect of Bifidobacterium Longum (BL NCC3001) on Psychological Symptoms | Baseline to 6 weeks. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Irritable Bowel Severity Scoring System (IBS-SSS) Bloating severity | Day -1, Day 43 (± 2 days) | 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). |
| Patient Health Questionnaire (PHQ-12) | Day -1, Day 43 (± 2 days) | 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. |
| Sheehan Disability Scale (SDS) | Day -1, Day 43 (± 2 days) | 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. |
| Amount of Bifidobacterium Longum (BL NCC3001) present in stool | Day -1, Day 43 (± 2 days) | Change from baseline to Week 6 |
| Irritable Bowel Severity Scoring System (IBS-SSS) score | Day -1, Day 71 (± 2 days) | 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. |
| Hospital Anxiety Depression Scale (HADS) total score | Day -1, Day 71 (± 2 days) | 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). |
| Rescue Medication | Day 43 (± 2 days) | Difference in proportions compared to placebo at Week 6 |
| Psychological distress improvement according to the Patient's Global Impression of Change of Psychological Distress | Day 43 (± 2 days) | 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. |
| Active treatment randomization perception: Do you think you have taken the placebo or active treatment? | Day 43 (± 2 days) | Difference in proportions compared to placebo at Week 6 |
| Hospital Anxiety Depression Scale - Depression (HADS-D) score | Day -1, Day 43 (± 2 days) | 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). |
| Hospital Anxiety Depression Scale - Anxiety (HADS-A) score | Day -1, Day 43 (± 2 days) | 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). |
| Depression Anxiety Stress Scale (DASS-21) | Day -1, Day 43 (± 2 days) | 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. |
| Perceived Stress Scale (PSS) | Day -1, Day 43 (± 2 days) | 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. |
| Irritable Bowel Severity Scoring System (IBS-SSS) Pain severity | Day -1, Day 43 (± 2 days) | 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). |
| Irritable Bowel Severity Scoring System (IBS-SSS) Pain frequency | Day -1, Day 43 (± 2 days) | 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). |
| Irritable Bowel Severity Scoring System (IBS-SSS) Bowel habit | Day -1, Day 43 (± 2 days) | 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). |
| Irritable Bowel Severity Scoring System (IBS-SSS) Life impact | Day -1, Day 43 (± 2 days) | 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). |
| Irritable Bowel Syndrome Quality of Life questionnaire (IBS-QoL) | Day -1, Day 43 (± 2 days) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Microbiota metabolic activity in urine - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days) | Changes in microbiota metabolic activity in urine |
| Cortisol levels in saliva - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days) | Change in cortisol levels in saliva |
| Biomarkers in blood - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days) | Detection of Biomarkers in blood |
| Neurotransmitters in blood - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days) | Detection of Neurotransmitters in blood |
| Amount of Bifidobacterium Longum (BL NCC3001) in stool | Day 71 (± 2 days) | Amount of Bifidobacterium Longum (BL NCC3001) in stool |
| Microbiota composition - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days), Day 71 (± 2 days) | Changes in microbiota composition in feces |
| Microbiota metabolic activity in feces - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days) | Changes in microbiota metabolic activity in feces |
| Microbiota metabolic activity in blood - A subset of 80 subjects (40 per arm) | Day -1, Day 43 (± 2 days) | Changes in microbiota metabolic activity in blood |
Countries
Canada
Outcome results
None listed