Randomized Clinical Study

Partially Hydrolyzed Guar Gum (PHGG) Versus Placebo in the Treatment of Patients With Irritable Bowel Syndrome

E. Niv; A. Halak; E. Tiommny; H. Yanai; H. Strul; T. Naftali; N. Vaisman

Disclosures

Nutr Metab. 2016;13(10) 

In This Article

Methods

This prospective randomized double blind placebo-controlled study was performed in the Clinical Nutrition Unit of Tel-Aviv Sourasky Medical Center (TASMC) in collaboration with the Departments of Gastroenterology in TASMC and in Sapir Medical Center, Israel. The study protocol was approved by the TASMC Helsinki committee (Number TLV-0242-12) and was registered in the NIH (NCT01779765). The patients were recruited from the medical centers' outpatient clinics. They were screened according to the study inclusion criteria and their willingness to participate. All recruited patients provided informed consent. The inclusion criteria were as follows: (1) fulfillment of the Rome III criteria for IBS, (2) availability of at least one gastrointestinal (GI) imaging study during the last five years (colonoscopy, sigmoidoscopy, abdominal ultrasonography, barium enema) for patients older than 50 years, (3) age 18–77 years at the time of screening, (4) provision of written informed consent, and (5) commitment of availability throughout the 18-week study period. The exclusion criteria were: (1) major abdominal surgery in the past, (2) the presence of any active (organic) GI disease, (3) past or present major medical or psychiatric illness, (4) alarming symptoms (rectal bleeding, weight loss, etc.), (5) pregnancy, (6) family history of colorectal carcinoma at age younger than 50 years or a family history of IBD, (7) abnormal laboratory studies (blood biochemistry, liver enzymes, complete blood count, abnormal thyroid function, celiac serology), (8) non-adjusted diet in the case of lactose intolerance, (9) recent travel to regions with endemic parasitic diseases, (10) probiotics or prebiotics administration two weeks prior to entry into the trial and (11) antibiotic use at least 3 months prior to entry into the trial.

All types of IBS were included in the study. Based on their dominant complaint, the patients were classified as constipation-predominant, diarrhea-predominant and mixed types. According to Rome III criteria, IBS with constipation was defined as: hard or lumpy stools ≥25% and loose (mushy) or watery stools <25% of bowel movements, IBS with diarrhea— as loose (mushy) or watery stools ≥25% and hard or lumpy stool <25% of bowel movements, Mixed IBS-- as hard or lumpy stools ≥ 25% and loose (mushy) or watery stools ≥25% of bowel movements.

The overall length of the study was 18 weeks (two weeks for the run-in period, 12 weeks of treatment and four weeks of follow-up) and was conducted between January 2013 and December 2014 (recruitment & follow up). The randomization list was made by the medical center's clinical trials pharmacy, using a block randomization of varying block size. The pharmacy staff were not involved in the conduct of the study. All of the clinical nutrition unit staff & participants were blinded during the whole trial. Patients were randomly assigned to one of two groups and received either PHGG (Sunfiber produced by Taiyo Kagaku Co., Ltd., Japan) in a dosage of three g/day for the first seven days and then six g/day for 11 weeks or placebo (Maltodextrin) in a dosage of three g/day for the first seven days and then six g/day for 11 weeks. Maltodextrin is a polysaccharide that is used as a food additive. It is produced from starch by partial hydrolysis and is usually found in the form of a white hygroscopic spray-dried powder. The patients were instructed to dissolve the sachet that contained either 6 g PHGG or placebo in a glass of water and to drink one glassful per day. Each patient was identified by a serial number, and the entire cohort underwent double blind randomization into the two groups (the study product and the placebo). They were asked not to not to take any probiotics or prebiotics during the study and to continue eating their usual diet and to take their usual medications.

A total of six visits were scheduled over the 18 weeks: the first visit at two weeks before the administration of the study product/placebo, three monthly visits during the ingestion of the study product/placebo and a follow-up visit at one month since the last ingestion of the study product/placebo. Demographic data were collected, a medical history was taken, inclusion/exclusion criteria were checked, informed consent was signed and the randomization took place at the first visit. The clinical severity of the IBS symptoms was evaluated by the Francis Severity IBS score and by the IBS quality-of-life (QOL) scores at each visit.[27,28] In addition, the patients filled out a self-reporting daily journal of the severity of symptoms. Adverse events and compliance were monitored throughout the study period.

The Francis Severity IBS score contains five questions, each given a value from 0 (no symptoms) to 100 (most severe) for measuring the severity and frequency of IBS-associated symptoms. The total Francis Severity IBS score is a sum of all the above and ranges from 0 to 500. The QOL questionnaire consists of 34 questions, each rated from 1 (mild) to 5 (severe), and their sum yields the total QOL score, ranging from 0 to 170. This questionnaire was validated for the Hebrew language.[29,30] The self-reporting daily journal was filled out for one week (each time at one week before the visit) and it consisted of several questions on abdominal pain, bloating, gasses and number of bowel movements per 24 h, and the score ranged from 0 to 70 for every question.

Statistical Analysis

The intention-to-treat analysis was performed on all patients who underwent randomization. An additional analysis included only those subjects who completed 12 weeks of study product/placebo administration. The primary endpoints were changes (delta) in the scores of journal parameters, the Francis Severity score, and the total QOL scores between the values at the end of treatment versus baseline and between the end of the follow-up period versus the baseline values. Comparisons of demographic and clinical variables as well as baseline severity and QOL scores between treatment and placebo groups were performed using Fisher's exact test and the Mann–Whitney non-parametric test, as applicable. Changes in values of all scores were examined using the mixed model for analysis of variance (ANOVA with repeated measures). This model allows the evaluations of the effect of each factor on the outcome as well as the interactions between the factors. The mixed model used group (treatment versus placebo) and time as factors. A P value of 0.05 was taken as significant.

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