This study aims to assess the clinical efficacy, safety and tolerance of a new formula containing a prebiotic and a mix of probiotics in the specific population of infants suffering from functional constipation through a superiority, double-blind, randomized, placebo-controlled trial.
The study comprises a selection period of 1 week where the eligibility of the infant to participate in the study will be evaluated. Once his/her participation is confirmed, the tested formula will be compared to a standard formula during a 2-month study period followed by an optional follow-up period of 2 months where only the tested formula will be used.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
80
New formula containing a prebiotic and a mix of probiotics, randomly assigned to infants during a 2-month period and allocated to all infants during the optional open-label follow-up period of 2 months.
Standard infant formula containing no prebiotic nor probiotic, randomly assigned to infants during a 2-month period followed by an optional open-label follow-up period of 2 months with the new infant formula
University of Naples "Federico II"
Naples, Italy
RECRUITINGUniversity of Campania Luigi Vanvitelli
Naples, Italy
NOT_YET_RECRUITINGHard stool consistency or painful defecation
Proportion of hard or painful stools per total number of spontaneous bowel movements by participant. A spontaneous bowel movement is defined as described in outcome 2. Stool consistency will be evaluated based on the Brussels Infant and Toddler Stool Scale (BITSS). BITSS is a reliable instrument to assess stools of non-toilet trained children. It consists of color photographs of nappies containing stools from infants and toddlers categorized as hard, formed, loose, or watery (Huysentruyt et al., 2019). The consistency and painful defecation of each stool will be assessed by parents at Day 30.
Time frame: 30 days
Total and spontaneous defecation frequency
Spontaneous bowel movement is defined as a bowel movement not produced by the use of rescue medication. Stools occurring within 24h after the use of rescue medication will not be considered spontaneous. If 2 stools occur within less than 1 hour, only 1 stool will be considered (Koppen et al., 2018). Defecation frequency will be assessed by parents by recording the time of each stool during the week preceding each visit.
Time frame: 30, 60, 90 and 120 days
Stool consistency
Parents will record the consistency of every stool the week preceding each visit as described in the outcome 1 using the BITSS scale (Brussels Infant and Toddler Stool Scale) which consists of 4 stools consistency categories (hard, formed, loose, or watery ; Huysentruyt et al., 2019)
Time frame: 30, 60, 90 and 120 days
Painful defecation
Painful defecation will be evaluated by parents for each stool during the week preceding each visit (Yes/No).
Time frame: 30, 60, 90 and 120 days
Excessive stool retention
"Excessive stool retention" is defined as "the infant withholding stools". It will be evaluated by parents at each visit (presence/absence).
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Time frame: 30, 60, 90 and 120 days
Large diameter stools
Large diameter stools will be assessed by parents at each visit using the picture of the largest stool in the BITSS as an example of the large diameter stool (presence/absence).
Time frame: 30, 60, 90 and 120 days
Treatment success
Treatment success is defined as no longer meeting the modified Rome IV criteria for functional constipation, i.e. the treatment will be considered as a success if the infant does not meet more than one of the following criteria per week during the week preceding each visit: 1. At least one painful or hard spontaneous bowel movement (Yes/No) 2. Two or fewer spontaneous defecations per week (Yes/No) 3. Excessive stool retention (Yes/No) 4. Large-diameter stools (assessed using the BITSS as described in the outcome 6) (Yes/No)
Time frame: 30, 60, 90 and 120 days
Rescue medication use
The frequency of use, type and dosage of rescue medication will be assessed by parents during the whole study.
Time frame: 30, 60, 90 and 120 days
Weight
Weight will be expressed in kg and in z scores according to the World Health Organization (WHO) Child Growth Standards.
Time frame: 30, 60, 90 and 120 days
Height
Height will be expressed in cm and in z scores according to the WHO Child Growth Standards.
Time frame: 30, 60, 90 and 120 days
Head circumference
Head circumference will be expressed in cm and in z scores according to the WHO Child Growth Standards.
Time frame: 30, 60, 90 and 120 days
BMI
BMI will be expressed in value and z scores according to the WHO Child Growth Standards.
Time frame: 30, 60, 90 and 120 days
Adverse events
Any untoward medical condition occurring during the study in an infant receiving study products regardless of a causal relationship with the product or not will be considered an adverse event and reported as such. This definition includes events occurring from the moment the parents have signed the Informed Consent form (day -7) up until the study end (or early termination).
Time frame: Through study completion, i.e. 67 days or 127 days if participation to the optional follow-up period
Nutritional status
Nutritional status will be assessed based on the evaluation of specific blood biological markers (albumin, creatinine, urea, hemoglobin, sodium, potassium, chloride).
Time frame: 0 and 60 days
Crying time
Daily crying duration will be assessed by parents on 3 days in the week preceding each visit.
Time frame: 30, 60, 90 and 120 days
Regurgitations
The number of regurgitation episodes, the volume of regurgitation and regurgitation severity will be assessed by parents on 3 days in the week preceding each visit. Regurgitation severity will be assessed through the Vandenplas score ranging from 0 (=less than 2 regurgitation episodes / day) to 6 (=regurgitation of the complete volume after each feeding).
Time frame: 30, 60, 90 and 120 days
Sleep quality
Sleep quality will be evaluated by parents at each visit by asking them if their child's sleep was quiet or agitated.
Time frame: 30, 60, 90 and 120 days
Sleep time satisfaction
Sleep time satisfaction will be evaluated by parents at each visit (Yes/No).
Time frame: 30, 60, 90 and 120 days
Parents' quality of life (QoL)
Parents' QoL will be assessed based on a questionnaire adapted from the Parental Opinions of Pediatric Constipation (POOPC) scale (Silverman et al., 2015). Questions from this scale were chosen based on their relevance to constipated infants. This questionnaire is composed of 4 items, i.e. Burden/Worry, Family, Treatment and Social. Each question is scored on a scale of 1 (=Strongly Disagree) to 5 (=Strongly Agree) with higher scores indicating that infant's constipation greatly affects parents' QoL. The total score is calculated by summing the scores of all individual question, ranging from 15 to 75 where a score of 15 indicates that infant's constipation does not affect parents' QoL whereas a score of 75 indicates that parents' QoL is extremely affected by infant's constipation.
Time frame: 30, 60, 90 and 120 days
Parents' satisfaction
Parents' adequate relief will be assessed at each visit (Yes/No).
Time frame: 30, 60, 90 and 120 days
Gut microbiota composition
Gut microbiota composition will be analyzed by 16S rRNA gene sequencing from stool samples.
Time frame: 0 and 60 days
Short-chain fatty acids (SCFAs)
SCFAs will be measured in stool samples by gas chromatography/mass spectrometry (GC/MS).
Time frame: 0 and 60 days