Effect of Probiotics on Functional Constipation in Adults (PROBCON)

The Effect of Probiotics on Functional Constipation in Adults: Double-blind, Randomized, Placebo-controlled Study

Introduction:

Functional constipation is a symptom-based gastrointestinal disorder without an organic origin (eg, bowel obstruction). It has a prevalence of 14% in adults.

Objective:

The objective of trial is to evaluate the efficacy and safety of two different probiotic blends in adults subjects with functional constipation.

Methods:

A double-blind, randomized, placebo-controlled study will be conducted for up to two years to evaluate the efficacy of two different probiotic mixtures: (Mixture 1) Lactobacillus acidophilus, Bifidobacterium bifidum and Lactobacillus rhamnosus (3 billion CFU); (Mixture 2) Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus rhamnosus, Lactobacillus paracasei, Bifidobacterium longum, Bifidobacterium lactis, Lactobacillus defensis, Bifidobacterium animallis (8 billion CFU).

Study Overview

• Status: Completed
• Conditions: Functional Constipation
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: 3 Billion UFC strains of probiotics; Dietary supplement: 8 Billion UFC strains of probiotics

Detailed Description

The study involve 150 healthy volunteers with functional constipation.The sample size was based on literature reviews of the probiotics' effect comparing the differences between means.

After confirmation of eligibility and obtaining written informed consent, the patients will be randomized (stratification for blocks) to recivied the interventions. The patients and the phisician will be blinded to the treatment received. The eligible patients will be allocated (1:1:1) to treatment with either the probiotics supplements or placebo. Subjects will be instructed to ingest one sachet before breakfast, by mixing the powder in water and drinking it. The sachets will be stored at room temperature.

Data handling and record keeping Case report forms will be used to record data for all participants, and will be completed by the research doctor, who will also enter the data into an electronic database.

Study schedule and location After inclusion, all further treatments will be managed at the primary care center where the subject was recruited. A research doctor and a research pharmacist will be responsible for all contacts with patients.

Local of study development Recruitment of patients to this study will be made by collaboration with the Gastroenterolgy Clinic at Avenue Dr Armando Sales de Oliveira 371, Trujilo, Sorocaba, State of São Paulo, Brazil from March 2020 to April 2020. Sorocaba is a Brazilian municipality in the interior of the state of São Paulo. It is the fourth most populous in the interior of São Paulo in the Southeast of the country, and the most populous in the southern region of São Paulo, with a population of 671,186 inhabitants, estimated by IBGE for July 1, 2018.

For comparison of three groups, an independent t-test will be applied for continuous variables and Mann-Whitney for non-continuous variables. Analysis of adverse events (if any) will be performed using Chi-Square test and Fisher's exact test following assumptions of randomness, independence and size. Significance differences will be set at p<0.05.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sorocaba, SP, Brazil, 19023000
      • Universidade de Sorocaba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-Clinical diagnosis of functional constipation according to Rome IV. Granting of written informed consent.

Exclusion Criteria:

• Presence of gastrointestinal diseases
• Ingestion of antibiotics or dietary supplements containing probiotics or prebiotics in the last 15 days
• Pregnancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; a) Control placebo (P1) Component Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet	Dietary supplement: Placebo; Fibers with vitamins and minerals will be administered for 30 days once a day in sachets; Other Names: Group Placebo
Active Comparator: 3 Billion CFU strains of probiotics; b) 3 Billion CFU (P2) Component Lactobacillus acidophilus LA 02 ID 1688 1 billion CFU,Bifidobacterium bifidum BB 01 ID 1722 1 billion CFU, Lactobacillus rhamnosus LR 04 ID 1132 1 billion CFU,Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet	Dietary supplement: 3 Billion UFC strains of probiotics; Fibers with vitamins and minerals will be administered for 30 days once a day in sachets with 3 billion CFU strains of probiotics
Active Comparator: 8 Billion CFU strains of probiotics; c) 8 Billion UFC (P3) Component Lactobacillus paracasei LPC 00 ID 1076 1 billion CFU;Bifidobacterium longum BL 03 ID 1152 1 billion CFU; Bifidobacterium lactis BS 01 ID 1195 1 billion CFU;Lactobacillus casei LC 03 ID 1872 1 billion CFU; Bifidobacterium animalis LMG 10508 1 billion CFU; Lactobacillus acidophilus LA 02 ID 1688 1 billion CFU,Bifidobacterium bifidum BB 01 ID 1722 1 billion CFU, Lactobacillus rhamnosus LR 04 ID 1132 1 billion CFU,Vitamin C (Ascorbic acid) 45 mg,Vitamin B1 (Thiamine) 1.1 mg, Vitamin B2 (Riboflavin) 1.1 mg,Vitamin D-3 40,000,000 IU / GR (Cholecalciferol) 34 mcg, Magnesium hydroxide 0.3 g, Calcium Carbonate 0.5 g, Natural Vanilla Flavor Powder 0.03 g,Fos (Fructooligosaccharides) qsp 3 g, for 30 days, once a day by sachet	Dietary supplement: 8 Billion UFC strains of probiotics; Fibers with vitamins and minerals will be administered for 30 days once a day in sachets with 8 billion CFU strains of probiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changed in the number of Bowel movements. Changed for more than 3 per week was considered a clinical response.	Changed number of bowel movements evaluated weekly	30 days
Change in the Bristol stool form scale at 4 weeks after Probiotics. Recovery to types 3-4 was considered a clinical response.	The Bristol scale ranges from 1-7, with 1-2 being constipated, 3-5 normal and 6-7 diarrhea.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject withdrawal	The volunteers can withdraw from the study at any time by their own request, or can be withdrawn at any time at the discretion of the investigator for safety. Volunteers will also be withdrawn from the study in the event of treatment interruption for any reason, whether due to forgetfulness or to experiencing undue intestinal discomfort	30 days
Adverse events	Adverse events are undesirable signs or symptoms that occur during the study and whose cause may or may not be causal related to the treatment. All adverse events considered possibly, probably or related to the test product will be noted down on the patient's form.	30 days
Serious adverse events	Serious adverse events are defined as events that are fatal, life-threatening, disabling or result in hospitalization or prolonged stay, or result in malformation, whether related to the test product or otherwise. According to previous studies, probiotics are safe and any serious adverse event that could possibly, probably or be related to the test products will be considered unexpected. All unexpected serious adverse events will be reported to the physician. Any serious adverse event that may be related to the test product will immediately lead to discontinuation of the test product	30 days

Collaborators and Investigators

• Sponsor: Luciane Cruz Lopes
• Investigators: Principal Investigator: Fabiana R MITELMAO, master, Universidade de Sorocaba

Publications and helpful links

General Publications

• Mitelmao FCR, Hackel K, Bergamaschi CC, Gerenutti M, Silva MT, Balcao VM, Vila MMDC. The effect of probiotics on functional constipation in adults: A randomized, double-blind controlled trial. Medicine (Baltimore). 2022 Oct 28;101(43):e31185. doi: 10.1097/MD.0000000000031185.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): January 28, 2021

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Lactobacillus; Bifidobacterium
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: Fabiana Rosa

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No