To investigate the effect of a cows-milk-based formula supplemented with synbiotics from t=0 to t=21, t=42 and t=84 days after amoxicillin or amoxicillin/clavulanic acid treatment in toddlers aged 1, 2 and 3 years old on: - change in proportion of…
ID
Source
Brief title
Condition
- Gastrointestinal signs and symptoms
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Proportion of all species belonging to the genus Bifidobacterium out of total
species, at t=0, t=21, t=42 and t=84 days, based on qPCR, ITS and 16s rDNA
sequencing data.
- Composition of all species belonging to the genus Bifidobacterium at t=0,
t=21, t=42 and t=84 days, based on qPCR, ITS and 16s rDNA sequencing data.
Secondary outcome
1.
a. Proportion of bifidobacteria by qPCR at t=0, t=7, t= 14, t=28, t=35, t=49,
t=56, t=63, t=70, t=77 and t=84 days;.
b. Total microbiota composition by 16s rDNA sequencing at t=0,t=21, t=42 and
t=84 days;
c. Faecal pH and short-chain fatty acid (SCFA) levels of faecal samples at t=0
to t=21, t=42 and t=84 days;
d. Stool characteristics: consistency and frequency as reported in a weekly
diary using modified Bristol Stool Form Scale;
e. Gastrointestinal symptoms, deviating from normal, as documented in a weekly
diary.
2. The proportion and composition of bifidobacteria and total microbiota
composition in the intervention- and control group compared to the age matched
group.
Other endpoints
1. The amount of study product and cow*s milk consumed for compliance, as
reported in the diary;
2. Habitual dietary intake assessed with an FFQ of participants and its
association with proportion bifidobacteria at 42 and 84 days;
3. Habitual dietary intake assessed with an FFQ of the participants and its
association with microbiota composition at 42 and 84 days;
4. Habitual dietary intake assessed with an FFQ of the participants and its
association with stool characteristics at 42 and 84 days.
Explorative study endpoints
• Total microbiota composition, bifidobacteria specific ITS sequence, faecal pH
and SCFA composition, at all timepoints;
• Total microbiota composition and bifidobacteria specific ITS sequence at t=0
to t=21, t=42 and t=84 days assessed per breastfeeding duration group (e.g. no
breastfeeding, breastfeeding up to 3, 6, 9 or 12 months after birth).
Background summary
The microbiota refers to a diverse ecosystem of bacteria, archaea, viruses and
fungi that reside in and on our body, such as in our gastrointestinal-tract
(GI-tract). This gut microbiota is of great importance for human health and the
stability and composition of the gut microbiota plays a vital role in health
and wellbeing throughout life from as early as birth, or even before that. Oral
antibiotics have been used effectively to treat many bacterial infections in
humans. However, the use of antibiotics has many direct and indirect health
consequences. Directly it can lead to diarrhoea, skin rashes, nausea and fungal
infections. In addition, it is posited that microbiota disruptions, as caused
by antibiotic use, can have long-lasting effects such as the development of
diseases e.g. asthma, allergies, eczema, diabetes and gut related diseases such
as inflammatory bowel disease.
There are multiple options by which the microbiota can be helped to recover
after big changes like after the use of antibiotics. One of these options are
synbiotics, they have the properties of both probiotics and prebiotics and were
created to overcome difficulties such as survival of the probiotic in the
GI-tract. The synbiotic product used in this study was specifically selected
based on its safety record and previous positive effects in toddlers and
infants on higher bifidobacteria proportions.
Study objective
To investigate the effect of a cows-milk-based formula supplemented with
synbiotics from t=0 to t=21, t=42 and t=84 days after amoxicillin or
amoxicillin/clavulanic acid treatment in toddlers aged 1, 2 and 3 years old on:
- change in proportion of species belonging to the genus Bifidobacterium out of
total species
- change in composition of species belonging to the genus Bifidobacterium
Study design
A randomized study in 126 children with a duration of 12 weeks, of which 6
weeks of intervention (cows-milk-based formula supplemented with synbiotics) or
control (cow's milk) followed by 6 weeks of run-out.
In addition, there will be an age-matched group (n=40) to assess a normal
microbiota composition in children who have not received antibiotics.
Intervention
Participants will be randomized to the intervention or control group. The
intervention group will be asked to replace 2 cups of regular milk with 2 cups
of cows-milk-based formula supplemented with synbiotics (Bifidobacterium breve
M-16V with scGOS / lcFOS) per day, and drink this for 6 weeks. The ideal intake
is 2 x 120 mL per day. The maximum intake is 500 mL per day. In the run-out
period during the last 6 weeks, participants will drink as normal.
The control group will continue to drink regular milk as they normally do
(standard care).
Study burden and risks
The cows-milk-based formula supplemented with synbiotics used in this study is
commercially available in France, Poland, Czech Republic and Slovakia and
produced in the Netherlands under the name CESARBIOTIK. Because of the long
safety record in children and presence in the gut microbiota, especially in
breastfed infants, Bifidobacterium breve M-16V is considered safe for
consumption. Moreover, the Food and Drug Administration (FDA) has a list of
Generally Recognized As Safe (GRAS) probiotics for the use in infant and
toddler formula, that includes Bifidobacterium breve M-16V, for which no
adverse events were reported. Therefore no side effects are expected. Only
non-invasive study procedures are included in the study. The YCF supplemented
with synbiotics may help speed up the recovery of the bifidobacteria
composition in toddlers after treatment with antibiotics.
Stippeneng 4
Wageningen 6708WE
NL
Stippeneng 4
Wageningen 6708WE
NL
Listed location countries
Age
Inclusion criteria
1. Written informed consent obtained from both caregivers;
2. Caregivers are willing to comply with the requirements of the study;
3. Aged 1 to 4 years old at the time of enrollment;
4. Drinks cow*s milk (non-fat, semi-skimmed or full fat) regularly;
5. Received a prescription for amoxicillin or amoxicillin / clavulanic acid*.
* There are no restrictions on use of any (other) antibiotics earlier in life.
Exclusion criteria
1. Any gastro-intestinal (GI) complaints, known structural GI abnormalities, or
previous GI surgery;
2. Clinically significant cardiac, vascular, liver, pulmonary, psychiatric
disorders, severe renal insufficiency, human immunodeficiency virus infection,
acquired immunodeficiency syndrome, hepatitis B or C or abnormalities of
haematology, urinalysis, or blood biochemistry;
3. Known to have an allergy or intolerance to any of the ingredients in the
study- or control product, including lactose and cow*s milk protein;
4. Is receiving breastmilk, or has received breastmilk in the last 7 days
before start of antibiotic treatment.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL75975.081.20 |
| Other | NL8996 |