Irritable Bowel Syndrome (IBS)BUZIRNCT04566679
Butyrate in Children With IBS: Double Blind Placebo Controlled Randomized Clinical Trial
A study testing Dibuzin in people with Irritable Bowel Syndrome (IBS) and Children, Only, run by University of Bari at 2 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 4 to 16 yearsHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome (IBS), Children, Only
- What is being tested?
- Dibuzin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesItaly
- Study dates
- 21 Apr 2021to 1 Jan 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 16 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Diagnosis of IBS according to the Rome IV diagnostic criteria
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Italy2 sites, 2 recruiting
- Recruiting
Clinica Pediatrica
Bari, Apulia, 70125
Ruggiero Francavilla, 080-5592360, rfrancavilla@libero.it
Ruggiero Francavilla, MD, PhD
- Recruiting
Pediatric Department "B Trambusti" Ospedale Giovanni XXIII Via Amendola 270
Bari, Ba, 70126
Fernanda Cristofori, 0805592847, fernandacristofori@gmail.com
Ruggiero Francavilla, MD
About this study
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.
Read the detailed 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.
- Conditions
- Irritable Bowel Syndrome (IBS), Children, Only
- Being tested
- Dibuzin, placebo
- Keywords
- Irritable Bowel Syndrome (IBS), children
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DibuzinDietary supplement
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)
placeboDietary supplement
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)
| Study group | Role | What they receive |
|---|---|---|
| Butyrate | Experimental | oral butyrate (500mg) once or twice per day Receives: Dietary Supplement: Dibuzin |
| Placebo | Placebo comparator | oral placebo once or twice per day Receives: Dietary Supplement: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: daily for 14 weeks
butyrate on GI symptoms
Gastrointestinal Symptom Rating Scale (GSRS)
Measured: every two weeks for 14 weeks
Secondary outcomes (1)
butyrate on inflammation
fecal calprotectin and lactoferrin
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2020
- Study start21 Apr 2021
- Primary completion1 Jan 2023 (estimated)
- Study completion1 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel Syndrome (IBS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bari
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ruggiero Francavilla, University of Bari
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04566679
- Sponsor's protocol ID
- BUZIR2020
- Acronym
- BUZIR
- Status last verified
- Apr 2021
- First submitted
- 18 Sep 2020
- Last updated
- 23 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. doi: 10.1136/gut.37.4.536.
PubMed 7489942Ogawa 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. doi: 10.1016/j.bbrc.2003.08.026.
PubMed 12963019Pozuelo 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.
PubMed 26239401Zhu 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.
PubMed 29977312Banasiewicz 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. 2013 Feb;15(2):204-9. doi: 10.1111/j.1463-1318.2012.03152.x.
PubMed 22738315von Baeyer CL. Children's self-reports of pain intensity: scale selection, limitations and interpretation. Pain Res Manag. 2006 Autumn;11(3):157-62. doi: 10.1155/2006/197616.
PubMed 16960632Svedlund J, Sjodin 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. doi: 10.1007/BF01535722.
PubMed 3123181Lussu M, Noto A, Masili A, Rinaldi AC, Dessi 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):1058-1066. doi: 10.1002/aur.1748. Epub 2017 Mar 11.
PubMed 28296209De 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. PLoS One. 2013 Oct 9;8(10):e76993. doi: 10.1371/journal.pone.0076993. eCollection 2013.
PubMed 24130822Cristofori F, Calabrese FM, Iacobellis I, Santamaria M, Celano G, Ferrocino I, Di Sabato E, Pergola R, Dargenio VN, Paulucci L, De Angelis M, Francavilla R. Calcium butyrate efficacy in pediatric irritable bowel syndrome: Randomized placebo-controlled multiomics-based clinical trial. J Pediatr Gastroenterol Nutr. 2025 Sep;81(3):551-561. doi: 10.1002/jpn3.70154. Epub 2025 Jul 9.
PubMed 40635319
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Butyrate in Children With IBS: Double Blind Placebo Controlled Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT04566679
- Acronym / sponsor ID
- BUZIR / BUZIR2020
- Conditions
- Irritable Bowel Syndrome (IBS), Children, Only
- Keywords
- Irritable Bowel Syndrome (IBS), children
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of BariUniversity, hospital or other
- Study start
- 21 Apr 2021 (actual)
- Primary completion
- 1 Jan 2023 (estimated)
- Study completion
- 1 Jan 2023 (estimated)
- First posted
- 28 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Butyrate | Experimental | Dietary Supplement: Dibuzinoral butyrate (500mg) once or twice per day |
| Placebo | Placebo comparator | Dietary Supplement: placebooral placebo once or twice per day |
Who may qualify
- Ages
- 4 to 16 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Diagnosis of IBS according to the Rome IV diagnostic criteria
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dibuzin2-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) | Dietary supplement | Butyrate |
| placebo2-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) | Dietary supplement | Placebo |
Primary outcome
butyrate on GI symptoms
Time frame: daily for 14 weeks
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.
butyrate on GI symptoms
Time frame: every two weeks for 14 weeks
Gastrointestinal Symptom Rating Scale (GSRS)
1 secondary outcome
butyrate on inflammation
Time frame: 14 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2021.
- Results publication: PubMed 7489942Gibson 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. doi: 10.1136/gut.37.4.536.
- Results publication: PubMed 12963019Ogawa 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. doi: 10.1016/j.bbrc.2003.08.026.
- Results publication: PubMed 26239401Pozuelo 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.
- Results publication: PubMed 29977312Zhu 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.
- Results publication: PubMed 22738315Banasiewicz 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. 2013 Feb;15(2):204-9. doi: 10.1111/j.1463-1318.2012.03152.x.
- Results publication: PubMed 16960632von Baeyer CL. Children's self-reports of pain intensity: scale selection, limitations and interpretation. Pain Res Manag. 2006 Autumn;11(3):157-62. doi: 10.1155/2006/197616.
- Results publication: PubMed 3123181Svedlund J, Sjodin 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. doi: 10.1007/BF01535722.
- Results publication: PubMed 28296209Lussu M, Noto A, Masili A, Rinaldi AC, Dessi 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):1058-1066. doi: 10.1002/aur.1748. Epub 2017 Mar 11.
- Results publication: PubMed 24130822De 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. PLoS One. 2013 Oct 9;8(10):e76993. doi: 10.1371/journal.pone.0076993. eCollection 2013.
- Derived from this study: PubMed 40635319Cristofori F, Calabrese FM, Iacobellis I, Santamaria M, Celano G, Ferrocino I, Di Sabato E, Pergola R, Dargenio VN, Paulucci L, De Angelis M, Francavilla R. Calcium butyrate efficacy in pediatric irritable bowel syndrome: Randomized placebo-controlled multiomics-based clinical trial. J Pediatr Gastroenterol Nutr. 2025 Sep;81(3):551-561. doi: 10.1002/jpn3.70154. Epub 2025 Jul 9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pediatric Department "B Trambusti" Ospedale Giovanni XXIII Via Amendola 270
Bari, Italy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dibuzin in people with Irritable Bowel Syndrome (IBS) and Children, Only, run by University of Bari at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
butyrate on GI symptoms (time frame: daily for 14 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04566679, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2021.