NCT02221687|Terminated

Study Stopped

Recruitment of breastfed infants was very slow. Decision with PI (05/2018): Termination (80/100); no implication on primary outcome. Predetermined number of breastfed infants (n=100) was arbitray choice. Formula groups completed (460/460) 12/2017.

The Combiotic-Study

GOLFIII

Evaluation of the Efficacy and Safety of an Infant Formula Containing Synbiotics and Its Effects on the Incidence of Infectious Diseases in the Infant Gut : a Double-blind, Randomized, Controlled Interventional Study

HiPP GmbH & Co. Vertrieb KG ClinicalTrials.gov

Compare

1 other identifier

505564 - PEC10561

Study Type

interventional

Target

540

Locations

1 country

Sites

Timeline

RegisteredAug 2014

StartedAug 2014

CompletionApr 2021

Brief Summary

The primary objective of this study is to demonstrate that a synbiotic formula, fed for the duration of the first year of life (infant and follow-on formula) reduces the incidence rate of episodes of infectious diarrhea in infants during the first year of life compared to a standard infant formula.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

540

participants targeted

Target at P75+ for not_applicable

Timeline

Completed

Started Aug 2014

Longer than P75 for not_applicable

Geographic Reach

1 country

25 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.7 years study duration

Study Start

First participant enrolled

August 1, 2014

Completed

18 days until next milestone

First Submitted

Initial submission to the registry

August 19, 2014

Completed

1 day until next milestone

First Posted

Study publicly available on registry

August 20, 2014

Completed

4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2019

Completed

2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2021

Completed

Last Updated

January 20, 2022

Status Verified

January 1, 2022

Enrollment Period

4.7 years

First QC Date

August 19, 2014

Last Update Submit

January 4, 2022

Conditions

Healthy Term Infants

Keywords

synbiotic formulainfant formuladiarrhea

Outcome Measures

Primary Outcomes (1)

(Cumulative) number of infectious diarrhea episodes per subject during the first year of life.
Difference between formula groups are evaluated via incidence rate based on number of subjects. In formula-fed infants, diarrhea is defined as three or more loose or watery stools in 24 hours with or without fever or vomiting (according to WHO and ESPGHAN definition). For breast-fed infants, a change in stool consistency versus previous stool consistency is more indicative of diarrhea than stool number. Diarrhea episode is considered as ended as soon as 2 consecutive non-watery stools are observed or no stools are observed in 24 hours.
one year

Secondary Outcomes (57)

Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
4 months
Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
1 year
Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
2 years
Analysis of fecal microbiota by molecular analysis from frozen stools in planned stool samples
3 years
Analysis of fecal microbiota by molecular analysis from frozen stools in diarrhea samples
1 year
+52 more secondary outcomes

Other Outcomes (6)

Microbiota results
1 year
Urinary D-Lactate and creatinine
4 weeks
Urinary D-Lactate and creatinine
4 months
+3 more other outcomes

Study Arms (3)

Synbiotic formula

EXPERIMENTAL

Synbiotic formula : standard formula enriched with a prebiotic fiber and a probiotic strain Dose : variable number of powder scoops, adapted to the infant's age and weight, and addition of the defined amount of water, according to the Dose and Drinking Amount table. Route : oral, ad libitum Duration of product intake: * Synbiotic IF : 5 months of consumption (from the inclusion until 6 months completed of age) * Synbiotic FoF: 6 months of consumption (from 6 to 12 months of age)

Dietary Supplement: Synbiotic formula

Control formula

PLACEBO COMPARATOR

Control formula : standard formula without pre and probiotic Dose : variable number of powder scoops, adapted to the infant's age and weight, and addition of the defined amount of water according to the Dose and Drinking Amount table. Route: oral, ad libitum Duration of product intake: * Control IF : 5 months of consumption (from the inclusion until 6 months completed of age) * Control FoF : 6 months of consumption (from 6 to 12 months of age)

Dietary Supplement: Control formula

Breast-fed group

NO INTERVENTION

\- Breast milk as exclusive feeding (no more than one formula meal per day), from birth until at least 4 months of age. Then, when the mother decides to stop breastfeeding, the infants can consume any formula on parent's choice respecting forbidden products list. Dose: * Breast milk : on demand Route : oral, ad libitum Duration of product intake: * Breast milk : at least 4 month (from birth until at least 4 months of age)

Interventions

Synbiotic formulaDIETARY_SUPPLEMENT

Standard milk formula enriched with a prebiotic fiber and a probiotic strain

Synbiotic formula

Control formulaDIETARY_SUPPLEMENT

Standard milk formula without pre and probiotic

Control formula

Eligibility Criteria

Age3 Weeks - 5 Weeks

Sexall

Healthy VolunteersYes

Age GroupsChild (0-17)

You may qualify if:

Healthy term infants
Female or male gender
Gestational age between 37 and 41 weeks completed (= 41 weeks + 6 days)
Age at time of V1 visit : 4 +/- 7 days
Birth weight between 2500 ans 4200g, with regular weight gain (≥ 150g / week)
Two legal representatives (parent(s) / guardian(s)) who are capable of and willing to comply with the protocol and have signed the informed consent in accordance with legal requirements.
at least one of the legal representatives is affiliated to with a social security scheme.
To be included in one of the formula arm, infants will have to be exclusively formula-fed (no breast milk meal) at the time of V1 visit (randomization).
To be included in the breastfeeding arm, infants will have to be exclusively breast-fed (no more than one formula meal per day) at V1 visit (randomization) and its mother will have to be willing to pursue exclusive breastfeeding at least until the infant will be 4-month old.

You may not qualify if:

Intensive care during at least the first 14 days of life
Neonatal health problems, such as: respiratory distress, asphyxia, hypoglycemia, sepsis, NEC (necrotizing enterocolitis),...
Clinical evidence of chronic illness or gastrointestinal disorders such as : GER (Gastrooesophageal Reflux), gastroenteritis,...
Known metabolic disorders, such as diabetes, lactose intolerance,....
Known immune deficiency
Subjects recommended to receive formula with hydrolized protein (e.g. children with allergy risk)
Subject under oral antibiotic treatment at V1 visit
Participation in another biomedical study
Whose legal representatives have psychological or linguistic incapability to sign the informed consent form
Reasons to presume that parents are unable to meet the study plan requirements (e.g. impossibility to contact study representatives in case of emergency, drug addiction etc)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

HiPP GmbH & Co. Vertrieb KGlead
Biofortis Mérieux NutriSciencescollaborator

Study Sites (25)

Elie JABBOUR

Gémozac, Charente-Maritime, 17260, France

Location

Christophe VIEL

La Rochelle, Charente-Maritime, 17000, France

Location

C.I.C Pédiatrique - C.H.U. de Grenoble - Hôpital Couple-Enfant

Grenoble, Isère, 38043, France

Location

C.I.C pédiatrique - C.H.U. de Nantes - Hôpital Mère-Enfant

Nantes, Loire-Atlantique, 44093, France

Location

Alain PALOMBA