Colic, InfantilePhase 4NEOBIFINCT03219931
NEOBIFI: Clinical Trial for the Prevention and/or Reduction of the Incidence of Colics in Infants
A Phase 4 study testing Bifidobacterium breve BR03 and Bifidobacterium breve B632 in people with Colic, Infantile and Probiotic, run by Azienda Ospedaliero Universitaria Maggiore della Carita at 1 site in Italy.
Trial summary
Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause.1 They can be associated with face redness, closed fists, thighs flexion, meteorism, and gas emission. Read more about this study
- Who is it for?
- Ages 6 to 15 daysHealthy volunteers can take part
- Conditions the study is for
- Colic, Infantile, Probiotic, Gut Microbiome
- What is being tested?
- Bifidobacterium breve BR03 and Bifidobacterium breve B632
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 320 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2013to 31 Jul 2017
- Phase
- Phase 4
- 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 6 to 15 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Only healthy babies term born
- Between 6 days and 15 days of life
- With a Birth weight between 2500 gr and 4000 gr
- With natural childbirth
Who cannot join
- Adverse reactions to the product or component of the product (allergies…)
- Antibiotic treatments
- Chronic diseases, hepatic or gastroenterological diseases
- Medical treatment for chronic diseases
- Probiotic or prebiotic therapies
Trial locations and contacts
1 site in 1 country.
Italy1 site
AOU Maggiore della Carità - Clinica Pediatrica - Ambulatorio di Gastroenterologia Pediatrica
Novara, 28100
About this study
Official title: Effects of an Association of the Two Bifidobacteria Probiotics Bifidobacterium Breve B632 and Bifidobacterium Breve BR03 in Intestinal Bacterial Colonization and in the Prevention and/or Reduction of the Incidence of Colics in Infants
Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause.1 They can be associated with face redness, closed fists, thighs flexion, meteorism, and gas emission. They are generally diagnosed according to Wessel's "rule of three" (>3 h of crying a day, for >3d a week, for >3wk in a row).2 These crises tend to reach their maximum intensity at 6 weeks of age, in most cases.3 They represent a serious source of anxiety for the family, increasing hospital admissions (5.8% of infants),4 postpartum depression risk, with higher stress levels for up to 3 years from these events. The etiology is still unknown. Anyway, it's assumed that the following factors may be involved: (1) Lactose intolerance. (2) Food hypersensitivity. (3) Feeding difficulties. (4) Disorders of the enteric nervous system. (5) Alterations of pain transmission. (6) Gastroesophageal reflux. (7) Intestinal hormones. (8) Psychosocial factors. (9) Alteration of the intestinal microbiota. In 1994, Lehtonen was the first to suggest that an altered intestinal microbiota composition in the very first months may induce intestinal colics in infants. Human intestinal microbiota is composed of about 1013 to 1014 microorganisms, mainly bacteria. The total number of microbiota genes is called "microbioma" and it is estimated to be 150 times the number of genes in the human genome.5 It acts as a real organ, whose activity can be influenced by diet, lifestyle, prebiotics, probiotics, and antibiotics. Several studies revealed the predominance of bifidobacteria in breastfed infants, whereas bottle-fed infants show a mixed population where bifidobacteria are less represented. the intestinal microbiota composition in a 3-year-old child is already similar to that of an adult.6 Other factors conditioning the microbiota are gestational age and type of birth. Colicky infants have a microbiota with a slow development and a lower stability over time.7 It also contains less lactobacilli and bifidobacteria, and a prevalence of gram-negative bacteria. The stools of these children often show increased levels of calprotectin, an intestinal index of inflammation.
RISK FACTORS ARE SEVERAL: Smoking: The exposure to cigarette smoke may be related to colics; this might be connected to the increase of plasma and intestinal levels of motilin. Maternal smoking during pregnancy seems to increase the risk of developing colics, more than postnatal exposition to smoke.8
Psychosocial: Infant colics may be more frequent with an instable psychosocial family environment. Maternal stress, anxiety, and depression are important risk factors.8 Breastfeeding: The difference between breastfeeding and bottlefeeding for colicky infants is controversial. Many studies have shown contrasting results,17 but the majority of the authors agree to attribute an important role to bottlefeeding. 9 A melatonin role was assumed too. This hormone is not secreted in infants, but only in adults, and has a hypnotic and relaxing role on the gastrointestinal smooth muscle. Its concentration shows a clear circadian rhythm, with a pick during night hours. Its presence in breast milk may be related to the lower occurrence of colics in breastfed infants compared with the bottle-fed infants.9 Recent literature shows an increasing attention toward probiotics,10 for the intestinal microbiota modulation. Some Lactobacillus reuteri strains were studied, with contrasting results in different studies; other probiotics as bifidobacteria showed in vitro anti-inflammatory properties and the ability to inhibit coliforms growth, whose presence is significant in colicky infants. Some probiotics exert a direct action on the bacterial growth, through bacteriocins production and final fermentation products.11 Bifidobacterium breve was isolated from healthy infants' feces.12 Aloisio et al13 tested in vitro ability of this strain and of other 45 bifidobacteria strains to oppose the growth of several microorganisms such as E. coli, S. enteriditis, C. difficile, K. pneumoniae, and Enterobacter cloacae. B. breve BR03, in a randomized clinical study, proved to have a beneficial effect on constipation in adults, it also seemed effective for the reduction of gas formation and for abdominal distension, and no side effects were shown during the treatment, while the beneficial effects lasted for up to 15 days after the end of the treatment.14,15 Both bifidobacteria strains showed, during an in vitro study, the ability to oppose 4 strains of E. coli; in particular, BR03 displayed an activity against E. coli O157:H7, an enterohemorrhagic strain that through Shiga toxin causes a potentially lethal infection.16
Read the detailed description
Type of Study: Interventional single-center, double-blind, randomized study, with treatment and placebo controlled.
Population: Only healthy babies were accepted. They were not treated with antibiotics, enrolled within 15 days from birth, and with an informed consent signed by the parents.
Parents were asked to make an initial recruitment examination within 15 days from birth and a second one at the 91st day of age, at the clinic of Pediatric Gastroenterology.
During the 90 days of the study, parents were asked to give 5 drops of active product (108 viable cells/strain) or placebo and to daily take note of minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits.
Probiotical S.p.A. (Novara, Italy) supplied the active product and the placebo. All data were collected in a database. Randomization was performed by an external operator of the study.
STATISTIC ANALYSIS:
Categorical variables were analyzed with the Fischer exact test. Comparisons between numeric variables between various groups were performed with the Kruskal-Wallis test (in the case of >2 groups) and with the Wilcoxon test for independent samples (in the case of only 2 groups being compared). A probability value of P<0.05 was considered as the limit of statistical significance.
- Conditions
- Colic, Infantile, Probiotic, Gut Microbiome, Bifidobacterium Breve
- Being tested
- Bifidobacterium breve BR03 and Bifidobacterium breve B632, Placebos
- Keywords
- infant colics, probiotic, gut microbiome, bifidobacterium breve, crying time
- Medical subject headings
- Colic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bifidobacterium breve BR03 and Bifidobacterium breve B632Drug
This is the active product containing 108 viable cells/strain
PlacebosDrug
Also called Placebo
This is the placebo product containing a similar product without bifidobacterium inside.
| Study group | Role | What they receive |
|---|---|---|
| Active group - Breastfeeding infants | Active comparator | In this Group will be enrolled only infants who are breastfed. This Group will take the active product containing 5 drops of active product (108 viable cells/strain) of Bifidobacterium breve BR03 and Bifidobacterium breve B632. Receives: Drug: Bifidobacterium breve BR03 and Bifidobacterium breve B632 |
| Active Group - Bottlefeeding infant | Active comparator | In this active Group will be enrolled only infant who are bottle-fed. This Group will take the active product containing 5 drops of active product (108 viable cells/strain) of Bifidobacterium breve BR03 and Bifidobacterium breve B632. Receives: Drug: Bifidobacterium breve BR03 and Bifidobacterium breve B632 |
| Placebo group - Breastfeeding infants | Placebo comparator | In this placebo Group will be enrolled only infants who are breastfed. This arm will receive a supplementation with a same product equal to the active product but without bifidobacterium inside. Receives: Drug: Placebos |
| Placebo group - Bottlefeeding infants | Placebo comparator | In this placebo Group will be enrolled only infants who are bottlefed. This arm will receive a supplementation with a same product equal to the active product but without bifidobacterium inside. Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in infants crying - reduction of infants crying
The primary endpoint of the study was the assessment of the effectiveness of B. breve B632 and BR03 association in the reduction of infants crying over time. Both breastfed and bottle-fed babies were studied.
Measured: Change from Baseline (V0) of infant crying at 3 months (V1)
Secondary outcomes (2)
Change in gastrointestinal symptoms
The second endpoint was to observe the effect of these probiotics on daily evacuations and on the number of regurgitations and vomits.
Measured: Change from Baseline (V0) of fecal evacuations, regurgitations and vomits at 3 months (V1)
Change in fecal microbiome
Evaluate any variation of fecal microbiome
Measured: Change from Baseline of fecal microbiome (V0) at 3 months (V1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2017
- Study start1 Oct 2013
- Primary completion31 Jul 2017
- Study completion31 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Colic, InfantileStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- During the 90 days of the study, parents were asked to give 5 drops of active product (108 viable cells/strain) or placebo and to daily take note of minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero Universitaria Maggiore della Carita
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flavia Prodam, Azienda Ospedaliero Universitaria Maggiore della Carita
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03219931
- Sponsor's protocol ID
- CE 63/13
- Acronym
- NEOBIFI
- Status last verified
- Jan 2018
- First submitted
- 14 Jul 2017
- Last updated
- 11 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Savino F. Focus on infantile colic. Acta Paediatr. 2007 Sep;96(9):1259-64. doi: 10.1111/j.1651-2227.2007.00428.x.
PubMed 17718777WESSEL MA, COBB JC, JACKSON EB, HARRIS GS Jr, DETWILER AC. Paroxysmal fussing in infancy, sometimes called colic. Pediatrics. 1954 Nov;14(5):421-35. No abstract available.
PubMed 13214956Kheir AE. Infantile colic, facts and fiction. Ital J Pediatr. 2012 Jul 23;38:34. doi: 10.1186/1824-7288-38-34.
PubMed 22823993Iacono G, Merolla R, D'Amico D, Bonci E, Cavataio F, Di Prima L, Scalici C, Indinnimeo L, Averna MR, Carroccio A; Paediatric Study Group on Gastrointestinal Symptoms in Infancy. Gastrointestinal symptoms in infancy: a population-based prospective study. Dig Liver Dis. 2005 Jun;37(6):432-8. doi: 10.1016/j.dld.2005.01.009. Epub 2005 Mar 2.
PubMed 15893282Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium; Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. doi: 10.1038/nature08821.
PubMed 20203603Brooks GF, Carroll KC, Butel JS, et al. Jawetz, Melnick, & Adelberg's Medical Microbiology, 26e. Columbus, OH: McGraw-Hill; 2013.
de Weerth C, Fuentes S, Puylaert P, de Vos WM. Intestinal microbiota of infants with colic: development and specific signatures. Pediatrics. 2013 Feb;131(2):e550-8. doi: 10.1542/peds.2012-1449. Epub 2013 Jan 14.
PubMed 23319531Yalcin SS, Orun E, Mutlu B, Madendag Y, Sinici I, Dursun A, Ozkara HA, Ustunyurt Z, Kutluk S, Yurdakok K. Why are they having infant colic? A nested case-control study. Paediatr Perinat Epidemiol. 2010 Nov;24(6):584-96. doi: 10.1111/j.1365-3016.2010.01150.x. Epub 2010 Aug 17.
PubMed 20955236Cohen Engler A, Hadash A, Shehadeh N, Pillar G. Breastfeeding may improve nocturnal sleep and reduce infantile colic: potential role of breast milk melatonin. Eur J Pediatr. 2012 Apr;171(4):729-32. doi: 10.1007/s00431-011-1659-3. Epub 2011 Dec 29.
PubMed 22205210WHO. WHO European Ministerial Conference on Nutrition and Noncommunicable Diseases in the Context of Health 2020. Vienna: WHO; 2013.
Sanders ME. Impact of probiotics on colonizing microbiota of the gut. J Clin Gastroenterol. 2011 Nov;45 Suppl:S115-9. doi: 10.1097/MCG.0b013e318227414a.
PubMed 21992949Scardovi V, Casalicchio F, Vincenzi N. Multiple electrophoretic forms of transaldolase and 6-phosphogluconic dehydrogenase and their relationships to the taxonomy and ecology of the bifidobacteria. Int J Syst Bacteriol. 1979;29:312-327.
Aloisio I, Santini C, Biavati B, Dinelli G, Cencic A, Chingwaru W, Mogna L, Di Gioia D. Characterization of Bifidobacterium spp. strains for the treatment of enteric disorders in newborns. Appl Microbiol Biotechnol. 2012 Dec;96(6):1561-76. doi: 10.1007/s00253-012-4138-5. Epub 2012 May 17.
PubMed 22588500Del Piano M, Carmagnola S, Anderloni A, Andorno S, Ballare M, Balzarini M, Montino F, Orsello M, Pagliarulo M, Sartori M, Tari R, Sforza F, Capurso L. The use of probiotics in healthy volunteers with evacuation disorders and hard stools: a double-blind, randomized, placebo-controlled study. J Clin Gastroenterol. 2010 Sep;44 Suppl 1:S30-4. doi: 10.1097/MCG.0b013e3181ee31c3.
PubMed 20697291Iemoli E, Trabattoni D, Parisotto S, Borgonovo L, Toscano M, Rizzardini G, Clerici M, Ricci E, Fusi A, De Vecchi E, Piconi S, Drago L. Probiotics reduce gut microbial translocation and improve adult atopic dermatitis. J Clin Gastroenterol. 2012 Oct;46 Suppl:S33-40. doi: 10.1097/MCG.0b013e31826a8468.
PubMed 22955355
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of an Association of the Two Bifidobacteria Probiotics Bifidobacterium Breve B632 and Bifidobacterium Breve BR03 in Intestinal Bacterial Colonization and in the Prevention and/or Reduction of the Incidence of Colics in Infants
- ClinicalTrials.gov ID
- NCT03219931
- Acronym / sponsor ID
- NEOBIFI / CE 63/13
- Conditions
- Colic, Infantile, Probiotic, Gut Microbiome, Bifidobacterium Breve
- Keywords
- infant colics, probiotic, gut microbiome, bifidobacterium breve, crying time
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- Azienda Ospedaliero Universitaria Maggiore della CaritaUniversity, hospital or other
- Study start
- 1 Oct 2013 (actual)
- Primary completion
- 31 Jul 2017 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 18 Jul 2017 (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.
Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause.1 They can be associated with face redness, closed fists, thighs flexion, meteorism, and gas emission. They are generally diagnosed according to Wessel's "rule of three" (>3 h of crying a day, for >3d a week, for >3wk in a row).2 These crises tend to reach their maximum intensity at 6 weeks of age, in most cases.3 They represent a serious source of anxiety for the family, increasing hospital admissions (5.8% of infants),4 postpartum depression risk, with higher stress levels for up to 3 years from these events. The etiology is still unknown. Anyway, it's assumed that the following factors may be involved: (1) Lactose intolerance. (2) Food hypersensitivity. (3) Feeding difficulties. (4) Disorders of the enteric nervous system. (5) Alterations of pain transmission. (6) Gastroesophageal reflux. (7) Intestinal hormones. (8) Psychosocial factors. (9) Alteration of the intestinal microbiota. In 1994, Lehtonen was the first to suggest that an altered intestinal microbiota composition in the very first months may induce intestinal colics in infants. Human intestinal microbiota is composed of about 1013 to 1014 microorganisms, mainly bacteria. The total number of microbiota genes is called "microbioma" and it is estimated to be 150 times the number of genes in the human genome.5 It acts as a real organ, whose activity can be influenced by diet, lifestyle, prebiotics, probiotics, and antibiotics. Several studies revealed the predominance of bifidobacteria in breastfed infants, whereas bottle-fed infants show a mixed population where bifidobacteria are less represented. the intestinal microbiota composition in a 3-year-old child is already similar to that of an adult.6 Other factors conditioning the microbiota are gestational age and type of birth. Colicky infants have a microbiota with a slow development and a lower stability over time.7 It also contains less lactobacilli and bifidobacteria, and a prevalence of gram-negative bacteria. The stools of these children often show increased levels of calprotectin, an intestinal index of inflammation.
RISK FACTORS ARE SEVERAL: Smoking: The exposure to cigarette smoke may be related to colics; this might be connected to the increase of plasma and intestinal levels of motilin. Maternal smoking during pregnancy seems to increase the risk of developing colics, more than postnatal exposition to smoke.8
Psychosocial: Infant colics may be more frequent with an instable psychosocial family environment. Maternal stress, anxiety, and depression are important risk factors.8 Breastfeeding: The difference between breastfeeding and bottlefeeding for colicky infants is controversial. Many studies have shown contrasting results,17 but the majority of the authors agree to attribute an important role to bottlefeeding. 9 A melatonin role was assumed too. This hormone is not secreted in infants, but only in adults, and has a hypnotic and relaxing role on the gastrointestinal smooth muscle. Its concentration shows a clear circadian rhythm, with a pick during night hours. Its presence in breast milk may be related to the lower occurrence of colics in breastfed infants compared with the bottle-fed infants.9 Recent literature shows an increasing attention toward probiotics,10 for the intestinal microbiota modulation. Some Lactobacillus reuteri strains were studied, with contrasting results in different studies; other probiotics as bifidobacteria showed in vitro anti-inflammatory properties and the ability to inhibit coliforms growth, whose presence is significant in colicky infants. Some probiotics exert a direct action on the bacterial growth, through bacteriocins production and final fermentation products.11 Bifidobacterium breve was isolated from healthy infants' feces.12 Aloisio et al13 tested in vitro ability of this strain and of other 45 bifidobacteria strains to oppose the growth of several microorganisms such as E. coli, S. enteriditis, C. difficile, K. pneumoniae, and Enterobacter cloacae. B. breve BR03, in a randomized clinical study, proved to have a beneficial effect on constipation in adults, it also seemed effective for the reduction of gas formation and for abdominal distension, and no side effects were shown during the treatment, while the beneficial effects lasted for up to 15 days after the end of the treatment.14,15 Both bifidobacteria strains showed, during an in vitro study, the ability to oppose 4 strains of E. coli; in particular, BR03 displayed an activity against E. coli O157:H7, an enterohemorrhagic strain that through Shiga toxin causes a potentially lethal infection.16
Detailed description
Type of Study: Interventional single-center, double-blind, randomized study, with treatment and placebo controlled.
Population: Only healthy babies were accepted. They were not treated with antibiotics, enrolled within 15 days from birth, and with an informed consent signed by the parents.
Parents were asked to make an initial recruitment examination within 15 days from birth and a second one at the 91st day of age, at the clinic of Pediatric Gastroenterology.
During the 90 days of the study, parents were asked to give 5 drops of active product (108 viable cells/strain) or placebo and to daily take note of minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits.
Probiotical S.p.A. (Novara, Italy) supplied the active product and the placebo. All data were collected in a database. Randomization was performed by an external operator of the study.
STATISTIC ANALYSIS:
Categorical variables were analyzed with the Fischer exact test. Comparisons between numeric variables between various groups were performed with the Kruskal-Wallis test (in the case of >2 groups) and with the Wilcoxon test for independent samples (in the case of only 2 groups being compared). A probability value of P<0.05 was considered as the limit of statistical significance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- During the 90 days of the study, parents were asked to give 5 drops of active product (108 viable cells/strain) or placebo and to daily take note of minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits.
| Arm | Type | Receives |
|---|---|---|
| Active group - Breastfeeding infants | Active comparator | Drug: Bifidobacterium breve BR03 and Bifidobacterium breve B632In this Group will be enrolled only infants who are breastfed. This Group will take the active product containing 5 drops of active product (108 viable cells/strain) of Bifidobacterium breve BR03 and Bifidobacterium breve B632. |
| Active Group - Bottlefeeding infant | Active comparator | Drug: Bifidobacterium breve BR03 and Bifidobacterium breve B632In this active Group will be enrolled only infant who are bottle-fed. This Group will take the active product containing 5 drops of active product (108 viable cells/strain) of Bifidobacterium breve BR03 and Bifidobacterium breve B632. |
| Placebo group - Breastfeeding infants | Placebo comparator | Drug: PlacebosIn this placebo Group will be enrolled only infants who are breastfed. This arm will receive a supplementation with a same product equal to the active product but without bifidobacterium inside. |
| Placebo group - Bottlefeeding infants | Placebo comparator | Drug: PlacebosIn this placebo Group will be enrolled only infants who are bottlefed. This arm will receive a supplementation with a same product equal to the active product but without bifidobacterium inside. |
Who may qualify
- Ages
- 6 to 15 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Only healthy babies term born
- Between 6 days and 15 days of life
- With a Birth weight between 2500 gr and 4000 gr
- With natural childbirth
Key exclusion criteria (5 listed)
- Adverse reactions to the product or component of the product (allergies…)
- Antibiotic treatments
- Chronic diseases, hepatic or gastroenterological diseases
- Medical treatment for chronic diseases
- Probiotic or prebiotic therapies
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 |
|---|---|---|
| Bifidobacterium breve BR03 and Bifidobacterium breve B632This is the active product containing 108 viable cells/strain | Drug | Active Group - Bottlefeeding infant, Active group - Breastfeeding infants |
| PlacebosAlso: PlaceboThis is the placebo product containing a similar product without bifidobacterium inside. | Drug | Placebo group - Bottlefeeding infants, Placebo group - Breastfeeding infants |
Primary outcome
Change in infants crying - reduction of infants crying
Time frame: Change from Baseline (V0) of infant crying at 3 months (V1)
The primary endpoint of the study was the assessment of the effectiveness of B. breve B632 and BR03 association in the reduction of infants crying over time. Both breastfed and bottle-fed babies were studied.
2 secondary outcomes
Change in gastrointestinal symptoms
Time frame: Change from Baseline (V0) of fecal evacuations, regurgitations and vomits at 3 months (V1)
Change in fecal microbiome
Time frame: Change from Baseline of fecal microbiome (V0) at 3 months (V1)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2018.
- Background: PubMed 17718777Savino F. Focus on infantile colic. Acta Paediatr. 2007 Sep;96(9):1259-64. doi: 10.1111/j.1651-2227.2007.00428.x.
- Background: PubMed 13214956WESSEL MA, COBB JC, JACKSON EB, HARRIS GS Jr, DETWILER AC. Paroxysmal fussing in infancy, sometimes called colic. Pediatrics. 1954 Nov;14(5):421-35. No abstract available.
- Background: PubMed 22823993Kheir AE. Infantile colic, facts and fiction. Ital J Pediatr. 2012 Jul 23;38:34. doi: 10.1186/1824-7288-38-34.
- Background: PubMed 15893282Iacono G, Merolla R, D'Amico D, Bonci E, Cavataio F, Di Prima L, Scalici C, Indinnimeo L, Averna MR, Carroccio A; Paediatric Study Group on Gastrointestinal Symptoms in Infancy. Gastrointestinal symptoms in infancy: a population-based prospective study. Dig Liver Dis. 2005 Jun;37(6):432-8. doi: 10.1016/j.dld.2005.01.009. Epub 2005 Mar 2.
- Background: PubMed 20203603Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Dore J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium; Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. doi: 10.1038/nature08821.
- BackgroundBrooks GF, Carroll KC, Butel JS, et al. Jawetz, Melnick, & Adelberg's Medical Microbiology, 26e. Columbus, OH: McGraw-Hill; 2013.
- Background: PubMed 23319531de Weerth C, Fuentes S, Puylaert P, de Vos WM. Intestinal microbiota of infants with colic: development and specific signatures. Pediatrics. 2013 Feb;131(2):e550-8. doi: 10.1542/peds.2012-1449. Epub 2013 Jan 14.
- Background: PubMed 20955236Yalcin SS, Orun E, Mutlu B, Madendag Y, Sinici I, Dursun A, Ozkara HA, Ustunyurt Z, Kutluk S, Yurdakok K. Why are they having infant colic? A nested case-control study. Paediatr Perinat Epidemiol. 2010 Nov;24(6):584-96. doi: 10.1111/j.1365-3016.2010.01150.x. Epub 2010 Aug 17.
- Background: PubMed 22205210Cohen Engler A, Hadash A, Shehadeh N, Pillar G. Breastfeeding may improve nocturnal sleep and reduce infantile colic: potential role of breast milk melatonin. Eur J Pediatr. 2012 Apr;171(4):729-32. doi: 10.1007/s00431-011-1659-3. Epub 2011 Dec 29.
- BackgroundWHO. WHO European Ministerial Conference on Nutrition and Noncommunicable Diseases in the Context of Health 2020. Vienna: WHO; 2013.
- Background: PubMed 21992949Sanders ME. Impact of probiotics on colonizing microbiota of the gut. J Clin Gastroenterol. 2011 Nov;45 Suppl:S115-9. doi: 10.1097/MCG.0b013e318227414a.
- BackgroundScardovi V, Casalicchio F, Vincenzi N. Multiple electrophoretic forms of transaldolase and 6-phosphogluconic dehydrogenase and their relationships to the taxonomy and ecology of the bifidobacteria. Int J Syst Bacteriol. 1979;29:312-327.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bifidobacterium breve BR03 and Bifidobacterium breve B632 in people with Colic, Infantile and Probiotic, run by Azienda Ospedaliero Universitaria Maggiore della Carita at 1 site 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 4 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: finished, as of the sponsor's last update on 11 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in infants crying - reduction of infants crying (time frame: Change from Baseline (V0) of infant crying at 3 months (V1)). 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 NCT03219931, which also lists 23 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 11 Jan 2018.