Butyrate in Children With IBS: Double Blind Placebo Controlled Randomized Clinical Trial

Children, Only Clinical Trial

— BUZIR  

Official title:

Butyrate in Children With IBS: Double Blind Placebo Controlled Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04566679
• Other study ID #: BUZIR2020
• Status: Recruiting
• Phase: N/A
• Start date: April 21, 2021
• Est. completion date: January 1, 2023

Study information

• Verified date: April 2021
• Source: University of Bari
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We will perform a randomized, double-blind, placebo-controlled trial to establish whether calcium butyrate relieves symptoms in children with irritable bowel syndrome (IBS). The direct effects of butyrate on inflammation and GI symptoms will be studied in children with IBS. The design used to study the effects of calcium butyrate will be a double blind randomized placebo-controlled parallel design.

Description:

Study plan 2-week run-in phase (weeks 1-2) followed by 8-week treatment period (weeks 3-10) and a 4- week follow-up phase (weeks 11-14).

Randomization Enrolled children will be randomly assigned, with the use of a computer-generated randomization list to receive either oral butyrate (500 mg) or oral placebo once (twice) per day. Placebo and butyrate had the same shape, the placebo's taste, dimension, indication, and appearance.

Data Collection A diary will be given to the parents; on a daily basis, patients will monitor and record the frequency/severity of symptoms and school absence on the diary. To assess the severity of pain, a combination of the self-reported visual analog scale (VAS) and the Faces Pain Scale (FPS) will be used. The 0- to 10-mm VAS scale (0, no pain; 10, worst possible pain) include a horizontal color gradient (green to red) plus a rating. Daily, when asked to evaluate pain, the child would point to a level and trace a line. Assessment will be done coupling the VAS with the FPS, which consists of 6 faces that range from a relaxed face to a face that shows intense pain (von Baeyer CL). GSRS Participants will be asked to fill out the GSRS every 2 weeks during running in, treatment, and follow up (Svedlund).

Compliance To ensure compliance, the investigator will contact the families every 4 weeks to monitor the process of the study.

Adherence will be assessed by counting the number of capsules returned; children who will miss taking more than 20% of the medication will be considered noncompliant.

Fecal Analysis Fecal samples for microbiological analysis will be collected before treatment and at week 10 (end of treatment) and week 14 (4 weeks after discontinuation). Urinary NMR Analysis Urinary samples for NMR analysis will be collected before treatment and at week 10 (end of treatment) and week 14 (4 weeks after discontinuation). This method is described by Lussu et al .

Fecal lactoferrin and calprotectin Fecal calprotectin will be measured using a commercial Fecal Calprotectin Immunoassay kit (Genova Diagnostics, Asheville, NC), respectively, following the manufacturers' instructions.

Sample size calculation To demonstrate an efficacy of butyrate, considering a placebo effect of 20% and a difference in response of at least 35%, keeping a power of the study of 80% and a p of 0,05 we need 23 patients for group that, considering a drop out of 10%, will became 25 per group.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 1, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 4 Years to 16 Years

Eligibility

Inclusion Criteria:

• Diagnosis of IBS according to the Rome IV diagnostic criteria

Exclusion Criteria:

• Presence of any chronic diseases

• Treatment with antibiotics/prebiotics/probiotic/postbiotic in the previous two months

• Diagnosis of another functional GI disease

• Growth failure or others alarming signs of organic conditions

• Previous abdominal surgery

Related Conditions & MeSH terms

• Children, Only
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome (IBS)

Intervention

Dietary Supplement:
• Dibuzin
2-week run-in phase (weeks 1-2) followed by 8-week treatment period (weeks 3-10) and 4-week follow-up phase (weeks 11-14)
• placebo
2-week run-in phase (weeks 1-2) followed by 8-week treatment period (weeks 3-10) and 4-week follow-up phase (weeks 11-14)

Locations

Country	Name	City	State
Italy	Clinica Pediatrica	Bari	Puglia
Italy	Pediatric Department "B Trambusti" Ospedale Giovanni XXIII Via Amendola 270	Bari	Ba

Sponsors (1)

Lead Sponsor	Collaborator
University of Bari

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Banasiewicz T, Krokowicz L, Stojcev Z, Kaczmarek BF, Kaczmarek E, Maik J, Marciniak R, Krokowicz P, Walkowiak J, Drews M. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis. — View Citation

De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLo — View Citation

Gibson P, Rosella O. Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease. Gut. 1995 Oct;37(4):536-43. — View Citation

Lussu M, Noto A, Masili A, Rinaldi AC, Dessì A, De Angelis M, De Giacomo A, Fanos V, Atzori L, Francavilla R. The urinary (1) H-NMR metabolomics profile of an italian autistic children population and their unaffected siblings. Autism Res. 2017 Jun;10(6):1 — View Citation

Ogawa H, Rafiee P, Fisher PJ, Johnson NA, Otterson MF, Binion DG. Butyrate modulates gene and protein expression in human intestinal endothelial cells. Biochem Biophys Res Commun. 2003 Sep 26;309(3):512-9. — View Citation

Pozuelo M, Panda S, Santiago A, Mendez S, Accarino A, Santos J, Guarner F, Azpiroz F, Manichanh C. Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome. Sci Rep. 2015 Aug 4;5:12693. doi: 10.1038/srep12693. — View Citation

Svedlund J, Sjödin I, Dotevall G. GSRS--a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988 Feb;33(2):129-34. — View Citation

von Baeyer CL. Children's self-reports of pain intensity: scale selection, limitations and interpretation. Pain Res Manag. 2006 Autumn;11(3):157-62. Review. — View Citation

Zhu L, Ma Y, Ye S, Shu Z. Acupuncture for Diarrhoea-Predominant Irritable Bowel Syndrome: A Network Meta-Analysis. Evid Based Complement Alternat Med. 2018 May 27;2018:2890465. doi: 10.1155/2018/2890465. eCollection 2018. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	butyrate on GI symptoms	To assess the severity of pain, a combination of the self-reported visual analog scale (VAS) and the Faces Pain Scale (FPS) will be used. The 0- to 10-mm VAS scale (0, no pain; 10, worst possible pain) include a horizontal color gradient (green to red) plus a rating.	daily for 14 weeks
Primary	butyrate on GI symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	every two weeks for 14 weeks
Secondary	butyrate on inflammation	fecal calprotectin and lactoferrin	14 weeks