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