Clinical trial NCT05013060: The Efficacy of Sodium Butyrate and Probiotics in Patients With Irritable Bowel Syndrome
Official title: An Assessment of the Efficacy of Microencapsulated Sodium Butyrate and a Probiotic Mixture in Patients With Irritable Bowel Syndrome - a Randomized Double-blind Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: Probiotics
Butyric acid
Microencapsulated sodium butyrate
Lead sponsor: Nordic Biotic Sp. z o.o.
Sponsor class: INDUSTRY
Collaborators: name: Medical University of Lodz
First posted: 2021-08-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: According to current IBS management guidelines, probiotic administration reduces IBS-associated symptoms and improves the quality of life. The purpose of this study is to assess the effects of the combined formulation comprising microencapsulated sodium butyrate and a probiotic mixture of two Lactobacillus strains (L. rhamnosus and L. acidophilus) and three Bifidobacterium strains (B. longum, B. bifidum, and B. lactis) on the incidence and severity of clinical symptoms in patients diagnosed with irritable bowel syndrome (IBS) based on the Rome IV criteria.

Microencapsulated sodium butyrate is a short-chain fatty acid (SCFA) with biological effects on the gastrointestinal mucosa; it constitutes a key source of energy for enterocytes. Butyrate was shown to have a trophic effect on the colon epithelium and to help restore the disrupted structural and functional integrity of the gastrointestinal tract. These unique properties of sodium butyrate result in its beneficial effects on the abdominal symptoms (such as diarrhea, constipation, abdominal pain) in patients with IBS. This study will assess the effects of the mixture of sodium butyrate and multi-strain probiotic on the rate and severity of clinical symptoms in IBS patients, by taking into account their nutritional status and body composition.

Detailed description: The study schedule includes five visits:the screening/baseline visit, whose purpose is to qualify patients to be included in the study, the randomization visit (visit 0), at which patients will be given a probiotic/butyric acid or placebo, and three follow-up visits (at weeks 4, 8, and 12 after randomization).

All patients will undergo:

1. A physical examination - at each visit;
2. Nutritional status assessment - at visit 0 and at weeks 4 and 12 of treatment;
3. Anthropometric measurements - at visit 0 and at weeks 4 and 12 of treatment;
4. Body composition analysis via bioelectrical impedance analysis (BIA) with the use of a Bodystat machine - at visit 0 and at 4 and 12 weeks of treatment;
5. Laboratory tests (including complete blood count; liver function tests; bilirubin, amylase, creatinine, CRP, and glucose levels; electrolytes; and an SARS-CoV2 antigen cassette test conducted by a doctor) at the screening visit; and cytokines (IL-6 and macrophage inflammatory protein 1β (MIP-1ß)) at visit 0 and at weeks 4 and 12 of treatment;
6. Disease severity will be rated with the IBS symptom severity score (IBS-SSS) developed by Francis, Morris, and Whorwell, with mild, moderate, and severe cases indicated by scores of \<175, 175-300, and \>300, respectively. In addition, the following scales will be used to assess IBS treatment efficacy: IBS-Quality of Life (IBS-QOL), IBS-Global Improvement Scale (IBS-GIS), and IBS - Adequate Relief (IBS-AR).
7. The number and type of bowel movements will be assessed with the Bristol Stool Formation scale.

Eligibility criteria: Inclusion Criteria:

1. Males and females aged from 18 to 70 years, inclusive;
2. Good physical and mental condition assessed based on the patient's history and physical examination;
3. Laboratory test results (complete blood count, blood chemistry panel) within normal limits or considered not to be clinically significant by the Investigator; negative SARS-CoV-2 antibody test;
4. A voluntarily provided written informed consent;
5. Diagnosis of IBS based on the Rome IV criteria, e.g. recurrent abdominal pain at least one day a week for the last three months, associated with two or more of the following symptoms (these should be present for the last three months, with the onset of symptoms six months before diagnosis):

   * related to defecation
   * associated with a change in stool frequency and/or
   * associated with a change in stool form (appearance)

   Patients with any of the following forms of IBS will be included:
   * IBS-D - more than 25% of BSF type 6 and 7 stools, and less than 25% of type 1 and 2 stools.
   * IBS-C - more than 25% of BSF type 1 and 2 stools, with less than 25% of type 6 and 7 stools.
   * IBS-M - more than 25% of BSF type 6 and 7 stools and also more than 25% of type 1 and 2 stools.
   * at least moderate symptom severity defined as an IBS-SSS score of \>175 (5 items, maximum score 500).
6. The following medications are allowed during this study, provided they have been used at a stable dose and for at least 1 month prior to the study:

   1. contraceptive pills or intramuscular contraceptives,
   2. hormone replacement therapy (estrogen/progesterone),
   3. L-thyroxine,
   4. antidepressants at low doses (up to 25 mg of amitriptyline, nortriptyline, or selective serotonin reuptake inhibitor per day)
   5. antihypertensives at low doses (diuretics, angiotensin converting enzyme inhibitors angiotensin receptor antagonists).

Exclusion Criteria:

1. Unclassified IBS;
2. Cardiovascular disorders: uncontrolled hypertension (blood pressure \>170/100 mmHg), cerebrovascular disease;
3. Respiratory disorders (asthma, chronic obstructive pulmonary disease \[COPD\]).
4. Hepatic impairment (including status post cholecystectomy), renal impairment, and unexplained blood biochemistry abnormalities: serum creatinine levels over twice the upper limit of normal, AST or ALT levels over twice the upper limit of normal.
5. Gastrointestinal conditions other than IBS, including clinical or endoscopic diagnosis of gastroenteritis.
6. Endocrine disorders, including diabetes mellitus (fasting blood glucose \>11 mmol/L) and elevated TSH levels.
7. Severe neurological conditions, with psychosis;
8. Malignancy;
9. Pregnancy or breastfeeding;
10. Hypersensitivity to soy;
11. Lactose intolerance;
12. The use of gastrointestinal motility stimulants or dietary fiber supplements during the 2 weeks preceding the clinical study;
13. The use of antithrombotic drugs;
14. A surgical procedure scheduled during the course of the clinical study;
15. Current probiotic use and refusal to undergo a 3-month washout period;
16. Antibiotic therapy during the 3 months preceding the study;
17. Antibiotic use during the study;
18. Being included in another clinical study during the previous 3 months;
19. History of alcohol or substance;
20. Inability to strictly adhere to the Investigators' instructions regarding study procedures and protocol requirements.abuse.

Primary outcomes:
measure: Changes in severity of IBS symptoms using IBS Severity Scoring System (IBS-SSS)
timeFrame: Severity of symptoms from baseline at 4, 8 and 12 weeks of intervention
measure: Improvement or worsening of IBS global symptoms using Global Improvement Scale (IBS-GIS)
timeFrame: Improvement/worsening assessed after 4, 8 and 12 weeks of intervention
measure: Changes in an adequate relief
timeFrame: Adequate Relief after 4, 8 and 12 weeks of interventions
measure: Changes in Quality of Life
timeFrame: Quality of Life from baseline at 4, 8 and 12 weeks of intervention
Secondary outcomes:
measure: Changes in number and type of stools
timeFrame: From baseline for 12 weeks of intervention in 1 week intervals
measure: Changes in severity of pain
timeFrame: From baseline for 12 weeks of intervention in 1 week intervals
measure: Changes in flatulence/abdominal distension
timeFrame: From baseline for 12 weeks of intervention in 1 week intervals
measure: Changes in Body Mass Index (BMI)
timeFrame: From baseline at 4 and 12 weeks of intervention
measure: Body composition analysis
timeFrame: From baseline at 4 and 12 weeks of intervention
Other outcomes:
measure: Changes in interleukin 6 (IL-6) and macrophage inflammatory protein 1β (MIP-1ß) levels
timeFrame: From baseline at 4 and 12 weeks of intervention
Locations:
city: Łódź
country: Poland
facility: Medical University of Lodz
Study officials:
affiliation: Medical University of Lodz
name: Anita Gąsiorowska, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gasiorowska A, Romanowski M, Walecka-Kapica E, Kaczka A, Chojnacki C, Padysz M, Siedlecka M, Bierla JB, Steinert RE, Cukrowska B. Effects of Microencapsulated Sodium Butyrate, Probiotics and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome: A Study Protocol of a Randomized Double-Blind Placebo-Controlled Trial. J Clin Med. 2022 Nov 7;11(21):6587. doi: 10.3390/jcm11216587.