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Evaluation of the Efficacy of a New Specific Infant Formula in Case of Functional Constipation

Primary Purpose

Functional Constipation

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
new infant formula
Standard formula
Sponsored by
United Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Functional Constipation focused on measuring Constipation, Infants, Infant formula, Nutrition, Defecation, Prebiotic, Probiotics

Eligibility Criteria

1 Month - 12 Months (Child)All SexesDoes not accept healthy volunteers

Selection Criteria:

Infants presenting with constipation according to modified Rome IV criteria, i.e. they must present with 1 month the following:

  • Infants without spontaneous stools or with at least one painful or hard spontaneous bowel movement per week AND

  • At least one of the following:

    • Two and fewer spontaneous defecations per week
    • History of excessive stool retention
    • History of large-diameter stools

Non-selection Criteria (non-exhaustive list):

  • Preterm birth (<34 weeks of gestational age)
  • Exclusively or partially breastfed infants within 3 days prior to visit V-1
  • Infants with organic causes of constipation (e.g. coeliac disease, paediatric intestinal pseudo-obstruction, hypothyroidism, spina bifida, anorectal malformation or Hirschsprung's disease) or constipation secondary to endocrine, metabolic, neurologic or autoimmune disorders, surgery or drugs.
  • Infants on laxative treatment
  • Infants taking drugs that are known to affect gastrointestinal motility as well as any probiotic supplements
  • Infants treated with antibiotics
  • Infants with a known allergy to one of the formula ingredients (e.g. cow's milk proteins…)
  • Infants with anaemia who have been prescribed an oral iron supplement as treatment
  • Infants participating in another trial
  • Infants presenting with any other situation which, according to the investigator, may interfere with the study participation, or lead to a particular risk for the infant

Inclusion Criteria:

  • Infants having completed the selection period and still compliant with non-selection criteria
  • Infants being constipated according to modified Rome IV criteria based on information recorded in parents' diary during the week preceding visit V0 (inclusion visit)

Sites / Locations

  • University of Naples "Federico II"Recruiting
  • University of Campania Luigi Vanvitelli

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IT formula

Standard formula

Arm Description

The test product (IT formula) is an infant formula based on cow's milk proteins containing a high level of lactose, a prebiotic, a high concentration of magnesium and a mix of probiotics.

The control product is a standard infant formula based on cow's milk proteins containing usual lactose and magnesium content, no prebiotic nor probiotic.

Outcomes

Primary Outcome Measures

Hard 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.

Secondary Outcome Measures

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.
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)
Painful defecation
Painful defecation will be evaluated by parents for each stool during the week preceding each visit (Yes/No).
Excessive stool retention
"Excessive stool retention" is defined as "the infant withholding stools". It will be evaluated by parents at each visit (presence/absence).
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).
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: At least one painful or hard spontaneous bowel movement (Yes/No) Two or fewer spontaneous defecations per week (Yes/No) Excessive stool retention (Yes/No) Large-diameter stools (assessed using the BITSS as described in the outcome 6) (Yes/No)
Rescue medication use
The frequency of use, type and dosage of rescue medication will be assessed by parents during the whole study.
Weight
Weight will be expressed in kg and in z scores according to the World Health Organization (WHO) Child Growth Standards.
Height
Height will be expressed in cm and in z scores according to the WHO Child Growth Standards.
Head circumference
Head circumference will be expressed in cm and in z scores according to the WHO Child Growth Standards.
BMI
BMI will be expressed in value and z scores according to the WHO Child Growth Standards.
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).
Nutritional status
Nutritional status will be assessed based on the evaluation of specific blood biological markers (albumin, creatinine, urea, hemoglobin, sodium, potassium, chloride).
Crying time
Daily crying duration will be assessed by parents on 3 days in the week preceding each visit.
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).
Sleep quality
Sleep quality will be evaluated by parents at each visit by asking them if their child's sleep was quiet or agitated.
Sleep time satisfaction
Sleep time satisfaction will be evaluated by parents at each visit (Yes/No).
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.
Parents' satisfaction
Parents' adequate relief will be assessed at each visit (Yes/No).
Gut microbiota composition
Gut microbiota composition will be analyzed by 16S rRNA gene sequencing from stool samples.
Short-chain fatty acids (SCFAs)
SCFAs will be measured in stool samples by gas chromatography/mass spectrometry (GC/MS).

Full Information

First Posted
April 8, 2022
Last Updated
November 4, 2022
Sponsor
United Pharmaceuticals
Collaborators
Delta Consultants
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1. Study Identification

Unique Protocol Identification Number
NCT05340712
Brief Title
Evaluation of the Efficacy of a New Specific Infant Formula in Case of Functional Constipation
Official Title
Evaluation of the Efficacy of a New Specific Infant Formula With a Prebiotic and Probiotics in Case of Functional Constipation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 20, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Pharmaceuticals
Collaborators
Delta Consultants

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Functional Constipation
Keywords
Constipation, Infants, Infant formula, Nutrition, Defecation, Prebiotic, Probiotics

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Superiority, double-blind, randomized, placebo-controlled trial of 60 days followed by an optional 60 day, open-label follow-up period with the tested formula only
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The allocation of the formula to each infant is drawn according to a randomization list developed using a software by the clinical research organization in charge of statistics and known only to him until the blind is lifted, i.e. after the statistical analysis. A 1:1 double-blind randomisation will be computer-generated by block (in each center).
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
IT formula
Arm Type
Experimental
Arm Description
The test product (IT formula) is an infant formula based on cow's milk proteins containing a high level of lactose, a prebiotic, a high concentration of magnesium and a mix of probiotics.
Arm Title
Standard formula
Arm Type
Placebo Comparator
Arm Description
The control product is a standard infant formula based on cow's milk proteins containing usual lactose and magnesium content, no prebiotic nor probiotic.
Intervention Type
Dietary Supplement
Intervention Name(s)
new infant formula
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Standard formula
Other Intervention Name(s)
Novalac 1
Intervention Description
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
Primary Outcome Measure Information:
Title
Hard stool consistency or painful defecation
Description
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
Secondary Outcome Measure Information:
Title
Total and spontaneous defecation frequency
Description
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
Title
Stool consistency
Description
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
Title
Painful defecation
Description
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
Title
Excessive stool retention
Description
"Excessive stool retention" is defined as "the infant withholding stools". It will be evaluated by parents at each visit (presence/absence).
Time Frame
30, 60, 90 and 120 days
Title
Large diameter stools
Description
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
Title
Treatment success
Description
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: At least one painful or hard spontaneous bowel movement (Yes/No) Two or fewer spontaneous defecations per week (Yes/No) Excessive stool retention (Yes/No) Large-diameter stools (assessed using the BITSS as described in the outcome 6) (Yes/No)
Time Frame
30, 60, 90 and 120 days
Title
Rescue medication use
Description
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
Title
Weight
Description
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
Title
Height
Description
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
Title
Head circumference
Description
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
Title
BMI
Description
BMI will be expressed in value and z scores according to the WHO Child Growth Standards.
Time Frame
30, 60, 90 and 120 days
Title
Adverse events
Description
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
Title
Nutritional status
Description
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
Title
Crying time
Description
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
Title
Regurgitations
Description
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
Title
Sleep quality
Description
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
Title
Sleep time satisfaction
Description
Sleep time satisfaction will be evaluated by parents at each visit (Yes/No).
Time Frame
30, 60, 90 and 120 days
Title
Parents' quality of life (QoL)
Description
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
Title
Parents' satisfaction
Description
Parents' adequate relief will be assessed at each visit (Yes/No).
Time Frame
30, 60, 90 and 120 days
Title
Gut microbiota composition
Description
Gut microbiota composition will be analyzed by 16S rRNA gene sequencing from stool samples.
Time Frame
0 and 60 days
Title
Short-chain fatty acids (SCFAs)
Description
SCFAs will be measured in stool samples by gas chromatography/mass spectrometry (GC/MS).
Time Frame
0 and 60 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Selection Criteria: Infants presenting with constipation according to modified Rome IV criteria, i.e. they must present with 1 month the following: Infants without spontaneous stools or with at least one painful or hard spontaneous bowel movement per week AND At least one of the following: Two and fewer spontaneous defecations per week History of excessive stool retention History of large-diameter stools Non-selection Criteria (non-exhaustive list): Preterm birth (<34 weeks of gestational age) Exclusively or partially breastfed infants within 3 days prior to visit V-1 Infants with organic causes of constipation (e.g. coeliac disease, paediatric intestinal pseudo-obstruction, hypothyroidism, spina bifida, anorectal malformation or Hirschsprung's disease) or constipation secondary to endocrine, metabolic, neurologic or autoimmune disorders, surgery or drugs. Infants on laxative treatment Infants taking drugs that are known to affect gastrointestinal motility as well as any probiotic supplements Infants treated with antibiotics Infants with a known allergy to one of the formula ingredients (e.g. cow's milk proteins…) Infants with anaemia who have been prescribed an oral iron supplement as treatment Infants participating in another trial Infants presenting with any other situation which, according to the investigator, may interfere with the study participation, or lead to a particular risk for the infant Inclusion Criteria: Infants having completed the selection period and still compliant with non-selection criteria Infants being constipated according to modified Rome IV criteria based on information recorded in parents' diary during the week preceding visit V0 (inclusion visit)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anne-Sophie Garreau
Phone
0033-155372222
Email
as.garreau@novalac.com
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Thevret, Dr.
Phone
0033-155372222
Email
c.thevret@novalac.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annamaria Staiano, Prof.
Organizational Affiliation
Federico II University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Marc Benninga, Prof.
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Caterina Strisciuglio, Prof.
Organizational Affiliation
University of Campania "Luigi Vanvitelli"
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Naples "Federico II"
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Annamaria Staiano, Prof.
Phone
0039 0817462679
Email
staiano@unina.it
First Name & Middle Initial & Last Name & Degree
Annamaria Staiano, Prof.
Facility Name
University of Campania Luigi Vanvitelli
City
Napoli
ZIP/Postal Code
80138
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caterina Strisciuglio, Prof.
Email
caterinastrisciuglio@hotmail.it
First Name & Middle Initial & Last Name & Degree
Caterina Strisciuglio, Prof.

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30672767
Citation
Huysentruyt K, Koppen I, Benninga M, Cattaert T, Cheng J, De Geyter C, Faure C, Gottrand F, Hegar B, Hojsak I, Miqdady M, Osatakul S, Ribes-Koninckx C, Salvatore S, Saps M, Shamir R, Staiano A, Szajewska H, Vieira M, Vandenplas Y; BITSS working group. The Brussels Infant and Toddler Stool Scale: A Study on Interobserver Reliability. J Pediatr Gastroenterol Nutr. 2019 Feb;68(2):207-213. doi: 10.1097/MPG.0000000000002153.
Results Reference
background
PubMed Identifier
29380480
Citation
Koppen IJN, Saps M, Lavigne JV, Nurko S, Taminiau JAJM, Di Lorenzo C, Benninga MA. Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials. Neurogastroenterol Motil. 2018 Apr;30(4):e13294. doi: 10.1111/nmo.13294. Epub 2018 Jan 30.
Results Reference
background
PubMed Identifier
25840448
Citation
Silverman AH, Berlin KS, Di Lorenzo C, Nurko S, Kamody RC, Ponnambalam A, Mugie S, Gorges C, Sanghavi R, Sood MR. Measuring Health-Related Quality of Life With the Parental Opinions of Pediatric Constipation Questionnaire. J Pediatr Psychol. 2015 Sep;40(8):814-24. doi: 10.1093/jpepsy/jsv028. Epub 2015 Apr 2.
Results Reference
background

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Evaluation of the Efficacy of a New Specific Infant Formula in Case of Functional Constipation

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