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Effectiveness of Probiotics Stabilized With Cryoprotection Technology in Patients With Irritable Bowel Syndrome

Primary Purpose

Irritable Bowel Syndrome

Status
Completed
Phase
Not Applicable
Locations
Poland
Study Type
Interventional
Intervention
Probiotic
Maltodextrin
Sponsored by
Children's Memorial Health Institute, Poland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Irritable Bowel Syndrome focused on measuring Irritable Bowel Syndrome, probiotics

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male and female subjects of Caucasian race
  2. Age between 16 and 60 years (inclusive)
  3. Good physical, medical and mental status estimated on the basis of the medical history and a general clinical examination.
  4. Results of laboratory tests (hematology, clinical chemistry, serology, and urinalysis) within the normal range of the local laboratory or considered non-clinically significant by the investigator.
  5. Subjects who have provided freely their own written informed consent.
  6. Subjects available for the whole study period.

  7. Diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria, i.e. symptoms of recurrent abdominal pain or discomfort* and a marked change in bowel habit with symptoms experienced on at least three days a week of at least three months within last year. Pain/discomfort is related to a change in the appearance of stool, frequency of stool and improves with defecation.

    * "Discomfort" means an uncomfortable sensation not described as pain.

  8. The following subjects will be enrolled in the study:

    1. with diarrhea-predominant irritable bowel syndrome, i.e., persons, who have at least one stool of type 6 or type 7 in Bristol stool score (BSS) over at least 2 days a week
    2. with at least moderate form assessed using IBS-SSS (5 questions, maximum number of points 500); enrolled subjects with score >175 points Mild <175 points, Moderate 175-300 points, Severe >300 points.
  9. Subjects who are able to follow strictly the instructions of the investigational team regarding the study procedures and to fulfil the requirements of the protocol.

  10. The following medications are permitted during the course of the study, as long as they are used at a constant dosage and are commenced at least 1 month prior to study start:

    1. birth control pill, or depot intramuscular contraceptive preparation,
    2. estrogen-progesterone replacement therapy,
    3. L-thyroxine,
    4. low-dose antidepressants (up to 25 mg day of amitriptyline, nortriptyline, or selective serotonin reuptake inhibitor)
    5. low-dose antihypertensives in the diuretic, angiotensin-converting enzyme inhibitor or angiotensin II inhibitor classes.

Exclusion Criteria:

  1. Patients with cardiovascular disorders: uncontrolled hypertension (blood pressure > 170/100 mmHg), cerebrovascular diseases.
  2. Patients with respiratory disorders (asthma, chronic obstructive pulmonary disease [COPD]).
  3. Patients with hepatic disorders (including condition following cholecystectomy procedure) and renal disorders as well as abnormal results of biochemical blood tests without diagnosis: serum creatinine > 2 x upper limit of normal, AST or ALT > 2 x upper limit of normal.
  4. Patients with gastrointestinal disorders other than IBS, including clinically or endoscopic-confirmed gastroenteritis.
  5. Patients with endocrinological disorders, including patients with diabetes mellitus (fasting blood glucose concentration > 11 mmol/L), and TSH > normal.
  6. Patients with serious neurological disorders, psychosis.
  7. Patients with malignancies.
  8. Pregnant or lactating women.
  9. Soy hypersensitivity.
  10. The subject has been diagnosed with lactose intolerance and this can explain their symptoms (i.e., symptoms resolved or reduced significantly with lactose-free diet).
  11. Use of motility drugs or dietary fiber supplements within 2 weeks before study start.
  12. Patients, taking anti-coagulant medication.
  13. Plan to have surgery during the time of the study.
  14. Currently consuming probiotics and refuse to have a three months washout period.
  15. Recent antibiotic therapy within the last 3 month.
  16. Patients, who receive antibiotics during the study, will be excluded.
  17. Patients, enrolled in another clinical trial in the past 3 months.
  18. The subject has a history of alcohol or substance abuse.

Sites / Locations

  • The Children's Memorial Health Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Probiotic

Maltodextrin

Arm Description

Multistrain probiotic mixture consisting of two Lactobacillus strains (L. rhamnosus and L. acidophilus) and three Bifidobacterium strains (B. longum, B. bifidum and B. lactis) administered for 8 weeks in a dose 1,0E+10/day, 2x sachets/day (5,0E+9/cfu per sachet)

Placebo - Maltodextrin manufactured with an appearance, taste and packaging (sachets) identical to the probiotic mixture administarted for 8 weeks 2x sachets/day

Outcomes

Primary Outcome Measures

Improvement or worsening of IBS global symptoms using Global Improvement Scale (IBS-GIS)
IBS-Global Improvement Scale asseses IBS symptoms using a patient-defined 7 point Linkert scale ranging from symptoms substantially worse to substantially improved. Patients answer the question "Have you felt any change in the severity of your symptoms over the past 7 days compared to how you felt before the medicine was given? The answers are recorded based on the 7-point scale: = I feel that the symptoms have worsened significantly = I feel that the symptoms have moderately worsened = I feel that the symptoms have slightly worsened = I feel no change = I feel a slight improvement = I feel moderate improvement = I feel significant improvement IBS-GIS score indicates: improvement if is >4 or worsening if is<4, no change if is 4
Changes in severity of IBS symptoms using IBS Severity Scoring System (IBS-SSS)
IBS-Severity Scoring System is a 5-question survey that asks: 1. the severity of abdominal pain, 2. frequency of abdominal pain, 3. severity of abdominal distention, 4.dissatisfaction with bowel habit, and 5. interference with quality of life over the past 10 days. Subjects respond to each question on a 100-point visual analogue scale. Each of the five question generates a maximum score of 100 point, and total scores can range from 0-500 with higher scores indicating severe symptoms. A decrease of 50 points is associated with a clinically meaningful improvement.
Changes in adequate relief of IBS symptoms (IBS-AR)
IBS-Adequate Relief (IBS-AR) is a dichotomous single item that asks participants "Over the past week (7 days) have you had adequate relief of your IBS symptoms? The answer is YES or NO.
Changes in Quality of Life (IBS-QOL)
The IBS-Quality of Life (IBS-QOL) is a 34-item measure assessing the degree to which IBS interferes with patient quality of life. Each item is rated on a 5-point Likert scale, thus yielding a total score that has a theoretical range of 34 to 170, with higher scores indicating worse QOL.

Secondary Outcome Measures

Changes in type of stools
Type of stool assessed before intervention and then 3 times a week. Type of stools assessed using the Bristol Stool Scale. Bristol Scale is designed to classify faeces into seven groups: type 1-2 indicate constipation, type 3-4 are "normal" stools; type 5-7 indicate diarrhea.
Changes in severity of pain
The severity of pain assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no pain, and 1-4 the severity of pain with higher scores indicating worse pain.
Changes in flatulence
The severity of flatulence assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no flatulence, and points1-4 with higher scores indicating worse flatulence
Changes in feeling of incomplete evacuation of stool
The severity of incomplete evacuation of stool assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no feeling of incomplete evacuation of stool, and points1-4 with higher scores indicating worse feeling of incomplete evacuation of stool
Changes in number of bowel movements per day
Number of bowel movements per day assessed before intervention and then 3 times a week.

Full Information

First Posted
December 12, 2019
Last Updated
January 31, 2021
Sponsor
Children's Memorial Health Institute, Poland
Collaborators
Medical University of Lublin
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1. Study Identification

Unique Protocol Identification Number
NCT04206410
Brief Title
Effectiveness of Probiotics Stabilized With Cryoprotection Technology in Patients With Irritable Bowel Syndrome
Official Title
Evaluation of the Effectiveness of Probiotics Stabilized With Cryoprotection Technology in Patients With Irritable Bowel Syndrome - a Randomized Double-blind, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
September 10, 2019 (Actual)
Study Completion Date
December 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Memorial Health Institute, Poland
Collaborators
Medical University of Lublin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Irritable bowel syndrome (IBS) is one of the most common diseases of the digestive tract in adults, which pathogenesis is not fully understood. It is assumed that intestinal dysbiosis affecting the functioning of the gut-brain axis may be important. Probiotics are live microorganisms that, when administered at the right dose, have a positive effect on human health. Probiotic mechanism of action is related to the modulation of intestinal microbiota. Clinical studies confirm that probiotics administered to patients with IBS have positive health effects. Clinical effects depend primarily on the selection of probiotic strains, but no less important is their viability and stability in the preparation administered to patients. Unfortunately, obtaining stability (a strictly defined number of live probiotic strains in the preparation throughout the shelf life of the preparation) is very technologically difficult. As shown by the audit of the Polish Supreme Audit Office (NIK), almost 90% of probiotics sold on the Polish market do not meet these criteria. There were probiotic preparations that by the end of their expiration date had less than 100 live bacterial cells from the declared number of about one billion. The only preparations that successfully passed NIK inspections turned out to be preparations in which the technology of double microcapsulation of bacteria was used. New technologies are constantly being sought that increase both the survival of bacterial strains in the preparation and the resistance of the strains to hydrochloric acid and bile, which in turn contributes to delivering the right dose of probiotics to the target site of activity, i.e. the small and large intestine. Recent developed an innovative technology called bacterial cryoprotection, which, compared to traditional lyophilization, leads to an increase in the stability of the bacterial cell wall membranes and protects them against negative factors both external (high temperature, humidity etc.) and internal (gastric acid, bile). Therefore, the purpose of the clinical trial is to assess the effectiveness of cryoprotected probiotics in patients with IBS.
Detailed Description
A 1- to 2-week screening period will be used to establish the presence and persistence of trial entry criteria and train patients in the mode of data collection. The screening period will also be used to select patients with specified levels of severity of signs and symptoms. During screening visit patients will undergo physical examination. Severity of IBS will be determined using the Francis, Morris and Whorwell's IBS severity scale (IBS-SSS): Mild <175, Moderate 175-300, Severe >300. Number and type of stools will be measured in all patients using Bristol stool scale. All eligible patients who sign informed consent form will be randomized within 2 weeks to receive either probiotic product or placebo and will complete Quality of Life assessment measured using IBS-QOL questionnaire. They will also be instructed to restrain from consuming foods and dietary supplements containing probiotics according to the clinical study requirements. After receiving probiotic product/placebo, telephone interviewers will call patients 3 times per week, and they will collect the following information by the phone: type of stools (according to Bristol Stool Score), number of bowel movements per day and IBS symptoms measured in 5-point scale (abdominal pain, flatulence, feeling of incomplete evacuation). In addition, telephone interviewers will collect information regarding adverse effects and using new drugs during the study. Patients will report to the doctor 2 times during study every 4 weeks during 8 week lasting intervention to receive new dose of probiotic product/placebo and to be assessed by the doctor using IBS-SSS, IBS-GIS and IBS-AR questionnaires, They will also complete Quality of Life questionnaire.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Irritable Bowel Syndrome
Keywords
Irritable Bowel Syndrome, probiotics

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Probiotic
Arm Type
Experimental
Arm Description
Multistrain probiotic mixture consisting of two Lactobacillus strains (L. rhamnosus and L. acidophilus) and three Bifidobacterium strains (B. longum, B. bifidum and B. lactis) administered for 8 weeks in a dose 1,0E+10/day, 2x sachets/day (5,0E+9/cfu per sachet)
Arm Title
Maltodextrin
Arm Type
Placebo Comparator
Arm Description
Placebo - Maltodextrin manufactured with an appearance, taste and packaging (sachets) identical to the probiotic mixture administarted for 8 weeks 2x sachets/day
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotic
Intervention Description
Multispecies probiotic mixture administered to patients according to the randomization list
Intervention Type
Dietary Supplement
Intervention Name(s)
Maltodextrin
Intervention Description
Maltodextrin as placebo
Primary Outcome Measure Information:
Title
Improvement or worsening of IBS global symptoms using Global Improvement Scale (IBS-GIS)
Description
IBS-Global Improvement Scale asseses IBS symptoms using a patient-defined 7 point Linkert scale ranging from symptoms substantially worse to substantially improved. Patients answer the question "Have you felt any change in the severity of your symptoms over the past 7 days compared to how you felt before the medicine was given? The answers are recorded based on the 7-point scale: = I feel that the symptoms have worsened significantly = I feel that the symptoms have moderately worsened = I feel that the symptoms have slightly worsened = I feel no change = I feel a slight improvement = I feel moderate improvement = I feel significant improvement IBS-GIS score indicates: improvement if is >4 or worsening if is<4, no change if is 4
Time Frame
Improvement/worsening of global symptoms after 4 and 8 weeks of intervention
Title
Changes in severity of IBS symptoms using IBS Severity Scoring System (IBS-SSS)
Description
IBS-Severity Scoring System is a 5-question survey that asks: 1. the severity of abdominal pain, 2. frequency of abdominal pain, 3. severity of abdominal distention, 4.dissatisfaction with bowel habit, and 5. interference with quality of life over the past 10 days. Subjects respond to each question on a 100-point visual analogue scale. Each of the five question generates a maximum score of 100 point, and total scores can range from 0-500 with higher scores indicating severe symptoms. A decrease of 50 points is associated with a clinically meaningful improvement.
Time Frame
From baseline at 4 and 8 weeks of intervention
Title
Changes in adequate relief of IBS symptoms (IBS-AR)
Description
IBS-Adequate Relief (IBS-AR) is a dichotomous single item that asks participants "Over the past week (7 days) have you had adequate relief of your IBS symptoms? The answer is YES or NO.
Time Frame
From baseline at 4 and 8 weeks of interventions
Title
Changes in Quality of Life (IBS-QOL)
Description
The IBS-Quality of Life (IBS-QOL) is a 34-item measure assessing the degree to which IBS interferes with patient quality of life. Each item is rated on a 5-point Likert scale, thus yielding a total score that has a theoretical range of 34 to 170, with higher scores indicating worse QOL.
Time Frame
From baseline at 4 and 8 weeks of intervention
Secondary Outcome Measure Information:
Title
Changes in type of stools
Description
Type of stool assessed before intervention and then 3 times a week. Type of stools assessed using the Bristol Stool Scale. Bristol Scale is designed to classify faeces into seven groups: type 1-2 indicate constipation, type 3-4 are "normal" stools; type 5-7 indicate diarrhea.
Time Frame
From baseline for 8 weeks of intervention
Title
Changes in severity of pain
Description
The severity of pain assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no pain, and 1-4 the severity of pain with higher scores indicating worse pain.
Time Frame
From baseline for 8 weeks of intervention
Title
Changes in flatulence
Description
The severity of flatulence assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no flatulence, and points1-4 with higher scores indicating worse flatulence
Time Frame
From baseline for 8 weeks of intervention
Title
Changes in feeling of incomplete evacuation of stool
Description
The severity of incomplete evacuation of stool assessed before intervention and then 3 times a week using a patient-defined 5 point Linkert scale: point 0 - no feeling of incomplete evacuation of stool, and points1-4 with higher scores indicating worse feeling of incomplete evacuation of stool
Time Frame
From baseline for 8 weeks of intervention
Title
Changes in number of bowel movements per day
Description
Number of bowel movements per day assessed before intervention and then 3 times a week.
Time Frame
From baseline for 8 weeks of intervention
Other Pre-specified Outcome Measures:
Title
Changes in serum level of intestinal fatty acid binding protein
Description
Intestinal fatty acid binding protein (I-FABP) is a novel serological marker of disrupted enterocytes, and could be an indicator of increased intestinal permeability. The level is measured in patients' sera using commercially available kits.
Time Frame
From baseline at 8 weeks of intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female subjects of Caucasian race Age between 16 and 60 years (inclusive) Good physical, medical and mental status estimated on the basis of the medical history and a general clinical examination. Results of laboratory tests (hematology, clinical chemistry, serology, and urinalysis) within the normal range of the local laboratory or considered non-clinically significant by the investigator. Subjects who have provided freely their own written informed consent. Subjects available for the whole study period. Diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria, i.e. symptoms of recurrent abdominal pain or discomfort* and a marked change in bowel habit with symptoms experienced on at least three days a week of at least three months within last year. Pain/discomfort is related to a change in the appearance of stool, frequency of stool and improves with defecation. * "Discomfort" means an uncomfortable sensation not described as pain. The following subjects will be enrolled in the study: with diarrhea-predominant irritable bowel syndrome, i.e., persons, who have at least one stool of type 6 or type 7 in Bristol stool score (BSS) over at least 2 days a week with at least moderate form assessed using IBS-SSS (5 questions, maximum number of points 500); enrolled subjects with score >175 points Mild <175 points, Moderate 175-300 points, Severe >300 points. Subjects who are able to follow strictly the instructions of the investigational team regarding the study procedures and to fulfil the requirements of the protocol. The following medications are permitted during the course of the study, as long as they are used at a constant dosage and are commenced at least 1 month prior to study start: birth control pill, or depot intramuscular contraceptive preparation, estrogen-progesterone replacement therapy, L-thyroxine, low-dose antidepressants (up to 25 mg day of amitriptyline, nortriptyline, or selective serotonin reuptake inhibitor) low-dose antihypertensives in the diuretic, angiotensin-converting enzyme inhibitor or angiotensin II inhibitor classes. Exclusion Criteria: Patients with cardiovascular disorders: uncontrolled hypertension (blood pressure > 170/100 mmHg), cerebrovascular diseases. Patients with respiratory disorders (asthma, chronic obstructive pulmonary disease [COPD]). Patients with hepatic disorders (including condition following cholecystectomy procedure) and renal disorders as well as abnormal results of biochemical blood tests without diagnosis: serum creatinine > 2 x upper limit of normal, AST or ALT > 2 x upper limit of normal. Patients with gastrointestinal disorders other than IBS, including clinically or endoscopic-confirmed gastroenteritis. Patients with endocrinological disorders, including patients with diabetes mellitus (fasting blood glucose concentration > 11 mmol/L), and TSH > normal. Patients with serious neurological disorders, psychosis. Patients with malignancies. Pregnant or lactating women. Soy hypersensitivity. The subject has been diagnosed with lactose intolerance and this can explain their symptoms (i.e., symptoms resolved or reduced significantly with lactose-free diet). Use of motility drugs or dietary fiber supplements within 2 weeks before study start. Patients, taking anti-coagulant medication. Plan to have surgery during the time of the study. Currently consuming probiotics and refuse to have a three months washout period. Recent antibiotic therapy within the last 3 month. Patients, who receive antibiotics during the study, will be excluded. Patients, enrolled in another clinical trial in the past 3 months. The subject has a history of alcohol or substance abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bożena Cukrowska, PhD MD
Organizational Affiliation
The Children's Memorial Health Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Memorial Health Institute
City
Warsaw
ZIP/Postal Code
04-730
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32635661
Citation
Skrzydlo-Radomanska B, Prozorow-Krol B, Cichoz-Lach H, Majsiak E, Bierla JB, Kosikowski W, Szczerbinski M, Gantzel J, Cukrowska B. The Effectiveness of Synbiotic Preparation Containing Lactobacillus and Bifidobacterium Probiotic Strains and Short Chain Fructooligosaccharides in Patients with Diarrhea Predominant Irritable Bowel Syndrome-A Randomized Double-Blind, Placebo-Controlled Study. Nutrients. 2020 Jul 5;12(7):1999. doi: 10.3390/nu12071999.
Results Reference
derived

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Effectiveness of Probiotics Stabilized With Cryoprotection Technology in Patients With Irritable Bowel Syndrome

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