Evaluation of the Efficacy of Two Probiotic Strains for Irritable Bowel Syndrome (14PIHL)

Evaluation of the Efficacy of Two Probiotic Strains for Irritable Bowel Syndrome: an 8-Week, Randomized, Placebo-Controlled Study

The purpose of this study is to determine if two different probiotic strains, Lactobacillus paracasei HA-196 and Bifidobacterium longum R0175, are effective in helping subjects manage the symptoms of IBS

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome
• Intervention / Treatment: Other: Placebo; Dietary supplement: Bifidobacterium longum R0175; Dietary supplement: Lactobacillus paracasei HA-196

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5R8
      • KGK Synergize Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female aged 18 years and older.

• IBS diagnosis according to Rome III criteria and referral to this study by a clinician. That is, recurrent abdominal pain or discomfort (i.e., uncomfortable sensation other than pain) at least 2 days/month in the last 3 months (response to question 1 of the IBS Rome III module questionnaire > 2) associated with 2 or more of the following:

  • Improvement with defecation (response to question 4 of the IBS Rome III module questionnaire > 0);
  • Onset associated with a change in stool frequency (response to question 5 or 6 of the IBS Rome III module questionnaire > 0);
  • Onset associated with a change in stool form (appearance). (response to question 7 or 8 of the IBS Rome III module questionnaire > 0).
• For women, the abdominal pain or discomfort should be experienced during days other than menstrual bleeding (response to question 2 of the IBS Rome III module questionnaire = 0 or 2)
• Criterion must be fulfilled for the last 3 months with symptom onset at least 6 months prior to screening (response to question 3 of the IBS Rome III module questionnaire = 1).
• A copy of the IBS module is provided in Appendix A: IBS Rome III Module Questionnaire
• Participants from the general population who have IBS symptoms, without a previous diagnosis, will be assessed by the Principle Investigator and included in the study if differential diagnosis confirms IBS. The Principle Investigator will confirm the diagnosis of IBS in any potential participants who have a previous diagnosis of IBS.
• Subjects experiencing a pain/discomfort frequency of at least 2 days a week during the run-in period. At visit 2, subjects will be asked "In the last 2 weeks, how often each week did you have discomfort or pain anywhere in your abdomen? ". The answer must be at least 2.
• Subjects diagnosed with IBS who have depression may be included
• Absence of black color (melena) or blood in stools.
• Willingness to complete questionnaires, records, and diaries associated with the study and to complete all clinic visits.
• Willingness to discontinue consumption of probiotics (e.g. yogurts, with live, active cultures or supplements).
• Able to provide informed consent.

Exclusion Criteria:

• Subjects with a history of suicidal ideation, or current suicidal ideation
• Previous history of gastrointestinal surgery (except appendectomy, cholecystectomy, hernia repair, or hemorrhoidectomy).
• Other gastrointestinal diseases (except hemorrhoids and uncomplicated diverticula), as assessed by ultrasonography, colonoscopy, or rectoscopy, or history of Clostridium difficile-associated diarrhea.
• A family history (immediate family i.e. siblings and parents) of colorectal cancer, inflammatory bowel disease and/or celiac spruce.
• Co-existing organic gastrointestinal disease.
• Presence of rectal bleeding, recent weight loss (greater than 5 kg in the past month) or iron deficiency anemia.
• History of, or current diagnosis of, liver disease, kidney disease, pulmonary disease, cardiovascular disease, pancreatic disease, any cancer.
• Presence of immune-compromised conditions such as AIDS, lymphoma or undergoing long-term corticosteroid treatment
• Presence or history of neurological disorders, or significant psychiatric illness.
• History of, or current diagnosis of, pelvic floor dyssynergia.
• Positive drug or alcohol screen or recent history of drug or alcohol abuse (within 3 years of screening).
• Milk or soy allergy.
• Use of another investigational product within 3 months of the screening visit. The screened participant could be eligible to participate after a washout period.
• Positive pregnancy test in women of child-bearing potential.
• Pregnant or breast-feeding or planning on becoming pregnant.

• Women of child-bearing potential not using effective contraception. Acceptable methods of birth control include:

  • 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)
  • Intrauterine devices
  • Vasectomy of partner (shown successful as per appropriate follow-up)
  • Double barrier method (use of physical barrier by both partners)
• Use of any antibiotic drug (e.g., neomycin, rifaximin) within 1 month of screening. The screened participant could be eligible to participate after a 1 month washout period.
• Use of PPI or H2R antagonist within 1 month of screening. The screened participant could be eligible to participate after a 1 month washout period.
• Daily use of non-steroidal anti-inflammatory drugs, cortisone, or other anti-inflammatory drugs 1 month prior to screening. The screened participant could be eligible to participate after a 1 month washout period.
• Current use, or use within the past 1 month, of narcotics or other medications for IBS symptom management (e.g. alosetron, tegaserod, lubiprostone, antispasmodics, antidiarrheals, laxatives, antipsychotics, tricyclic anti-depressants, selective serotonin reuptake inhibitors (SSRIs)). Subjects taking a stable dose of anti-depressants for at least 30 days with no plan to change dosage during the trial will be eligible for inclusion in the study.
• Regular use of anti-diarrhea medications and laxatives. Occasional use is permitted prior to screening (≤ than once a month); if current use is >once per month a one month wash out period is needed prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bifidobacterium longum R0175; 10 x 10^9 CFU per capsule, 1 capsule daily for 8 weeks	Dietary supplement: Bifidobacterium longum R0175
Experimental: Lactobacillus paracasei HA-196; 10 x 10^9 CFU per capsule, 1 capsule daily for 8 weeks	Dietary supplement: Lactobacillus paracasei HA-196
Placebo Comparator: Placebo; 1 capsule daily for 8 weeks	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IBS Symptom Severity Score	Assessed using IBS Severity Scoring System Questionnaire, Part I.	8 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IBS Symptom Severity Score by IBS Subtype	Assessed using IBS Severity Scoring System Questionnaire, Part I.	8 weeks
Number of Responders	A responder is defined as a participant who has at least a 20% improvement in the IBS-SSS severity score after 8 weeks of supplementation	8 weeks
Anxiety and Depression	Assessed by administering the HADS questionnaire	8 weeks
Abdominal pain frequency	Assessed using IBS Severity Scoring System Questionnaire, Part I(c)	8 weeks
Abdominal distension/tightness	Assessed using the IBS-SSS Question 2(b)	8 weeks
Abdominal Pain Intensity	Mean weekly score. Assessed using IBS-SSS	8 weeks
Severity of straining	Assessed using IBS daily diary, 5 point ordinal scale	8 weeks
Health Status	Assessed by administration of the SF-36 questionnaire	8 weeks
Impact of IBS symptoms on Quality of Life	Assessed by administration of the IBS-QOL Questionnaire	8 weeks
Severity of IBS Symptoms	Assessed by administration of the IBS-SSS questionnaire, difference from baseline to week 4	4 weeks
Bowel Habit Satisfaction	Assessed by question 3 of the IBS-SSS	8 weeks
Stool Consistency	Assessed using the Bristol Stool Scale included in the IBS Daily Diary	8 weeks
Stool Frequency	Assessed using the IBS Daily Diary	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance and Recovery of Probiotic strains	Monitored by qPCR of fecal samples	8 weeks
Microbiome Composition	Detected in fecal samples	8 weeks
Cysteine and serine-protease activity	Measured in stool samples	8 weeks
Amount of rescue medication used throughout the trial	Use of rescue medication (Bisacodyl 5mg tablet)	8 weeks
Safety Anthropometric Measurements	Blood pressure, Heart rate, Weight and BMI	8 weeks
Safety blood parameters	Complete blood count, electrolytes, markers of kidney and liver function	8 weeks
Number of Adverse Events occurring throughout the trial		8 weeks

Collaborators and Investigators

• Sponsor: KGK Science Inc.
• Collaborators: Lallemand Health Solutions

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2014
• Primary Completion (Actual): February 15, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 7, 2014
• First Posted (Estimate): August 11, 2014

Study Record Updates

• Last Update Posted (Actual): March 13, 2020
• Last Update Submitted That Met QC Criteria: March 11, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Constipation; IBS; Probiotic; Bifidobacterium longum; Lactobacillus paracasei; Lallemand Health Solutions
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: 14PIHL