Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02813772 |
| Other study ID # |
30/05/2016 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
June 14, 2016 |
| Last updated |
September 7, 2016 |
| Start date |
November 2015 |
| Est. completion date |
October 2016 |
Study information
| Verified date |
September 2016 |
| Source |
Federico II University |
| Contact |
Annamaria Staiano |
| Email |
staiano[@]unina.it |
| Is FDA regulated |
No |
| Health authority |
Italy: Ethics Committee |
| Study type |
Interventional
|
Clinical Trial Summary
Infant colic (IC) is responsible of 25% of pediatric consultation in the first 3-4 months of
life affecting from 5% to 30% of infants between 2 weeks and 3 months of life (3, 4). The
variability in the prevalence of IC reported by the several studies depends on different
criteria used to define IC.The etiology of IC remains still unclear. Recently, the
composition of intestinal microbiome has been addressed as an independent risk factor for
IC. There are no uniform criteria for a specific therapeutic approach of IC. Based on these
conclusions the objectives of our study are: to determine whether the administration of a
partially hydrolyzed formula (pHF) with reduced lactose content and Lactobacillus reuteri,
is beneficial in IC in reducing the infant crying duration and in prolonging the duration of
sleeping period
Description:
BACKGROUND Definition Infantile Colic (IC) is one of the Functional gastrointestinal
disorders (FGIDs) of infants/toddlers, which are defined as a variable combination of
chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical
abnormalities. In 2006, the Rome III committee established a new criteria defining it as
"episodes of irritability, fussing, or crying that begin and end for no apparent reason and
last at least three hours a day, at least three days a week, for at least one week".
Epidemiology IC is responsible of 25% of pediatric consultation in the first 3-4 months of
life affecting from 5% to 30% of infants between 2 weeks and 3 months of life. The
variability in the prevalence of IC reported by the several studies depends on different
criteria used to define IC.
In a systematic review of 15 community-based surveys on IC prevalence, carried out in 2001,
the occurrence rates in the first 3 months of life were from 3% to 28% in prospective
studies and from 8% and 40% in retrospective studies. In a prospective study found that
20.5% of 2879 Italian infants, aged 2 weeks-6 months, had IC.
Recently a French study reported a prevalence of IC in infants aged 0-4 months, of 19%. In
two english studies, IC was reported in 18.3% and 26 % respectively, of infants aged 0-12
months. Other European studies were conducted with a different reported prevalence.
Outside Europe, a prevalence of 9.2% and of 20% respectively were reported by two studies
carried out in US. More recently in an Israeli study of 94 mothers of 2-4 moths of life
infants, 56% of those whose babies were breastfed and 73% of those using formula reported
"paroxysmal irritability".
In addition, several studies found occurrence rates of crying/fussing problems in young
infants ranging from 7% to 19%, without defining the problems as IC.
Pathogenesis The etiology of IC remains still unclear. Gender, type of milk (breast-milk or
formula), delivery modality (vaginally or caesarean), mother age, number of siblings and
gestational history do not seem to be correlated to IC onset. Gastrointestinal function,
psychosocial, and neurodevelopmental disorders, food intolerance, transient low lactase
activity, cow's milk protein allergy (CMPA), gastro-esophageal reflux (GER) and intestinal
microbiota imbalance have been suggested as the cause of colic.
Gastrointestinal theories include increased intra-abdominal gas, hyperperistalsis and
visceral pain. Gastrointestinal disorders have been implicated in colic because of the
infant's leg position and grimacing during the crying episodes. Excessive crying or
increased gas production from colon function can result in intraluminal gas formation and
aerophagia, even if radiographic images taken during a crying episode have shown a normal
gastric outline. One study has suggested that infants with colic may have increased fecal
calprotectin levels, suggesting a possible role for gut inflammation; however, another study
suggested no differences in fecal calprotectin levels between infants with and infants
without colic. Gut hormones, such as motilin, also may play a causative role in colic.
Motilin is thought to cause hyperperistalsis, leading to abdominal pain and colic. Regarding
psychosocial hypotheses, maternal anxiety and depression, and difficult infant temperament
have been correlated to IC. Also behavioral issues such as family tension or inadequate
interaction between parents and infant have been considered, but these issues are really
controversial. Concomitant risk factors remain partially unknown; however, maternal smoking,
increased maternal age and firstborn status may be associated to the development of IC.
The role of intestinal microbiome in Infantile Colic Recently, the composition of intestinal
microbiome has been addressed as an independent risk factor for IC. Several studies indicate
that inadequate lactobacilli in the first few months of life may affect intestinal fatty
acid profile favoring the development of IC. Coliform bacteria have also been found more
abundantly in colicky infants and it is speculated that altering the intestinal microbiota
composition may positively influence the management of affected infants. As a matter of
fact, recently, research into the use of probiotics for colic has been rapidly increasing
but results are conflicting. Infants with colic are reported to have increased concentration
of gas forming organisms and proteobacteria such as Escherichia coli in their gut.
Colonization with certain intestinal microorganisms, such as Bifidobacterium and
Lactobacillus species, along with increased intestinal microbial diversity, may protect
against infant distress. Probiotics enhance the mucosal barrier and promote microbial
diversity in the gut. They may reduce concentrations of proteobacteria and gas forming
coliform and reduce intestinal inflammation.
One clinical trial showed safety and efficacy of Lactobacillus reuteri in prevention of IC.
A recent meta-analysis of three small, randomized controlled trials, of breast-fed infants
with IC reported that Lactobacillus reuteri noticeably reduced crying time at 21 days post
supplementation. Recently Chau et al showed that administration of Lactobacillus reuteri DSM
17938 significantly improved colic symptoms by reducing crying and fussing times in
breastfed Canadian infants with colic. In contrast, a double blind, placebo controlled
randomized trial on the same probiotic strain Lactobacillus reuteri DSM 17938 showed that it
did not benefit a community sample of breast-fed infants and formula-fed infants with IC.
The role of diet in Infant colic There are no uniform criteria for a specific therapeutic
approach of IC. Regarding dietary modifications on management of IC, current evidence
suggests that they may reduce IC in only a very small minority of infants. Unfortunately,
the evidence is often contrasting. For the breast-fed infants with IC, where there is the
relatively rare concern of a cow's milk protein allergy (CMPA), one can consider eliminating
cow's milk from the maternal diet for a minimum of two weeks. For the formula-fed infants
with colic, the use of a time-limited (two weeks) empiric trial of an extensively hydrolyzed
formula may be considered. However this information derived from studies in highly selected
patients from tertiary care level centers. In a double-blind, placebo-controlled trial, a
partial hydrolyzed, with high β-palmitate, and a specific prebiotics mixture with galacto-
and fructo-oligosaccharides resulted in a significant decrease of colic within one week of
intervention. In some cases, these formulas are lactose-reduced or lactose-free and contain
prebiotics or probiotics causing a reduction in the number of crying episodes per week and
total crying time. Infante et al showed an association between clinical improvement and
evidence of decreased levels of hydrogen in IC when the infants were fed with a specially
designed, low-lactose formula. Moreover, in two double-blinded crossover trials, lactase
treatment reduced crying time compared with placebo. The use of soy formulas, instead, in
the treatment of IC should be avoided since it can induce sensitization to soy and it's high
in isoflavones with estradiol-like effects.
OBJECTIVES
Primary objective:
-To determine whether the administration of a partially hydrolyzed formula (pHF) with
reduced lactose content and Lactobacillus reuteri, is beneficial in IC in reducing the
infant crying duration.
Secondary objectives:
- To evaluate the effect of a partially hydrolyzed formula (pHF) with reduced lactose
content and Lactobacillus reuteri in prolonging the duration of sleeping period.
- To evaluate the effect of this infant formula enriched with Lactobacillus reuteri on
fecal microbiome of colicky infants
- To evaluate the effect of this infant formula enriched with Lactobacillus reuteri on
parents' quality of life
- To evaluate the effect of this infant formula enriched with Lactobacillus reuteri on
infants' quality of life
METHODS
Study design
- This is a prospective, double-blind, randomized-controlled, clinical trial.
- The study aims to compare the infant colic's trend and intestinal microbiome between
infants fed with partially hydrolyzed formulas (pHF; 100% whey protein; 1.9g/100 kcal)
with reduced lactose content (40%), addition of maltodextrins (60%) and Lactobacillus
reuteri (NAN Sensitive, Nestlè) (group 1) and infants fed with an intact protein body
formula (70% of whey protein, 30% of casein; 1.85g/100 kcal) with 100% of lactose
content and not containing Lactobacillus reuteri (NAN Optipro 1, Nestlè) (group 2).
- Subjects will be enrolled consecutively and randomized to one of the 2 study groups.
