Impact of Probiotics BIFILACT® on Diarrhea in Patients Treated With Pelvic Radiation

In this double-blinded randomized clinical trial study, investigators assessed probiotic used to prevent or delay radiation induced grade moderate to severe diarrhea with patient treated for pelvic cancer.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Cancer; Abdominal Pain; Diarrhea
• Intervention / Treatment: Other: placebo; Drug: Bifilact®

Detailed Description

This study was prospective, unicentric, controlled with comparison to a placebo, randomised and double-blinded. Patients were stratified into three groups: prostatic cancers, gynecologic cancers without chemotherapy and gynecologic or rectal cancers with chemotherapy.

Patients were block-randomized by the research nurse and received a standard dose of Bifilact® probiotics or placebo according to the random list generated by blocks of 2, 4, or 6 patients according to random permutations. A preliminary internal pilot study was performed when the half of the expected sample size were recruited. The goal of this analysis was to test assumptions that lead to chosen sample sizes (N0) and thus, validate the feasibility of the study. Following preliminary results, the sample size re-calculated at the interim analysis is similar to that originally intended. It would be advisable to continue the recruitment as planned. No adjustment to the critical level of the test would be required in analyzes carried out at the end of study. However, another random block using higher probiotics dosage to the randomization was added with preservation of double bind. New random list were generated for each strata with a 3:1:1 ratio (higher dose, standard dose, placebo) to compensate for the starting of the latest higher dose group. All the bottles had a similar aspect, they were all identified by the commercial brand Bifilact. Also the group, either A, B or C, was circled on that bottle, depending on if that bottle belong to the placebo group, standard dose group, or high dose group. Only the nurse knew the coding system, it was also her who would assign the patient to a group, according to the randomization list. She would also hand out the bottle to the patient every week. The two registered dietician, caregivers, were totally excluded of this processes (preliminary study and randomisation) to preserve the double blind.

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Quebec city, Quebec, Canada, G1R 2J6
      • CHU de Québec, radio-oncology departement

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• They had a pelvic cancer: gynecologic, rectal, or prostatic,they were to receive radiotherapy treatments for a minimum of 40 Gy at the pelvic level , with or without chemotherapy and they had Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1

Exclusion Criteria:

• they had previous radiotherapy treatments in the pelvic or abdominal region, medical history of gastro-intestinal inflammation, malabsorption syndrome or inflammatory bowel disease or coeliac disease, ileostomy, daily use of anti-diarrheal medication before radiotherapy, pregnancy or breastfeeding, neutropenia or probiotics intolerance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bifilact® probiotics standard dose; concentration of 1.3 billion of Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536. one pill twice a day. Each capsule contained maltodextrin and magnesium stearate as excipient	Drug: Bifilact®; placebo, standard dose 1.3 billion twice a day, high dose 10 billion three time a day; Other Names: probiotics
Active Comparator: Bifilact® probiotics high dose; containing 10 billion Lactobacillus acidophilus LAC-361 and Bifidobacterium longum BB-536. One pill three times a day. Each capsule contained maltodextrin and magnesium stearate as excipient	Drug: Bifilact®; placebo, standard dose 1.3 billion twice a day, high dose 10 billion three time a day; Other Names: probiotics
Placebo Comparator: placebo; Each capsule contained maltodextrin and magnesium stearate as excipient. One pill twice a day	Other: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
testing the efficacy of probiotics Bifilact®, in comparison to a placebo to assess its ability to prevent or delay the incidence of moderate or severe symptoms of diarrhea during the period of treatment by radiotherapy	Patients were asked to note in a daily logbook whether they experienced digestive problems such as daily bowel movements. Severity of the diarrhea was evaluated according to toxicity criteria of the WHO: grade 1 = increase of 2-3 stools per day compared to pre-treatment, grade 2 = increase of 4-6 bowel stools per day or nocturnal stools, grade 3 = increase of 7-9 stools per day or incontinence, grade 4 = increase of 10 or more stools, need for IV hydration. The Registered Dietitian assessed symptoms in logbook with the patient once a week.The duration of daily logbook was 4-9 weeks depending of the total dose of external radiotherapy	day 1-60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary objectives were to assess whether intake of Bifilact® lowered the interruption of radiotherapy treatments or doses of both radiotherapy or chemotherapy	Registered Dietitian assessed respect of the preview protocol treatment each week (radiotherapy and chemotherapy) if not respected: diarrhea is it involved. For patients that received chemotherapy, a weekly blood profile was obtained and study pills were discontinued if neutrophil count became ≤1.5 X 10(9)/L.	week 1-9
Secondary objective were to assess whether intake of Bifilact® decreased or delayed the consumption of anti-diarrheal medication	Patients were asked to note, each day during the treatment,in a daily logbook intake of anti-diarrheal medication, laxatives, and antibiotics. The Registered Dietitian assessed symptoms noted with the patient each week.The duration of daily logbook was 4-9 weeks depending of the total dose of external radiotherapy	day 1-60
Secondary objectives were to assess whether intake of Bifilact® reduced abdominal pain	Abdominal pain was evaluated according to the NCI scale version 3.0: Grade 1 = mild pain, not interfering with function, grade 2 = moderate pain: pain or analgesics interfering with function, but not interfering with activity of daily living, grade 3 =: severe pain: pain or analgesics severely interfering with activity of daily living. The Registered Dietitian assessed information with the patient each week	day 1-60
Secondary objectives were to assess whether the overall well-being of patients was improved during treatment.	Quality of life (EORTC-QLQ-C30) assessment was filled three times during the study: once at the outset, once at the end, and then again two weeks after the last radiotherapy treatment.	week 0, 4-9, 6-11
Secondary objectives were to assess whether intake of Bifilact® decreased need for hospitalization	Registered Dietitian assessed each week if the patient had need hospitalization and if the diarrhea has involved	week 1-9

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Investigators: Study Director: Dagnault Anne, PhD, CHU de Québec; Principal Investigator: Josee Desjardins, B.Sc, RD, CHU de Québec; Principal Investigator: Mimi Demers, B.Sc. RD, CHU de Québec

Publications and helpful links

General Publications

• Demers M, Dagnault A, Desjardins J. A randomized double-blind controlled trial: impact of probiotics on diarrhea in patients treated with pelvic radiation. Clin Nutr. 2014 Oct;33(5):761-7. doi: 10.1016/j.clnu.2013.10.015. Epub 2013 Oct 24.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: April 16, 2013
• First Submitted That Met QC Criteria: April 22, 2013
• First Posted (Estimate): April 25, 2013

Study Record Updates

• Last Update Posted (Estimate): May 17, 2013
• Last Update Submitted That Met QC Criteria: May 16, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: nutrition; Probiotics; diet; radiation-induced enteritis; radiation-induced diarrhea; radiation, diarrhea, enteritis
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Diarrhea; Abdominal Pain
• Other Study ID Numbers: 5.7.06.09