A Randomized, Double-blinded, Parallel, Placebo-controlled Study to Investigate the Efficacy of Lb Paracasei [Junlebao Lp. N1115] as a Probiotic to Enhance Gut Development in Young Children
Phase: NA
Conditions: Intestinal Growth of Young Children
Sponsor: Junlebao Dairy Group Co., Ltd.

 
 
STUDY PROTOCOL 
 
 
Study Title:  
A randomized, double-blinded, parallel, placebo-controlled study to 
investigate the efficacy of Lb paracasei [Junlebao Lp. N1115] as a 
probiotic to enhance gut development in young children 
 
 
Brief Title: 
A Study on Efficacy of Feeding N1115 Probiotic Supplement to 
Young Children (N1115Baby) 
 
 
 SPONSOR: Shijiazhuang Junlebao Dairy Co.,Ltd. 
RESEARCHER: Atlantia Food Clinical Trials Ltd. 
Teagasc 
 
 
Date：01-11-2018 

1. STUDY PROTOCOL 
 
Name of Company: 
Shijiazhuang Junlebao Dairy Co.,Ltd. 
Study Product: 
Lactobacillus paracasei N1115 versus placebo 
Study Centre: 
Atlantia Food Clinical Trials Ltd 
Study Title: 
A randomised, double-blinded, parallel, placebo-controlled 
study to investigate the efficacy of Lb paracasei [Junlebao Lp. 
N1115] as a probiotic to enhance gut development in young 
children 
Study Design 
Randomised, parallel, double-blinded, controlled 
Objectives: 
Primary Objectives 
- 
Intestinal health (stool frequency, stool consistency, GI 
symptoms including flatulence, bloating, cramps and 
diarrhea) 
Secondary Objectives 
- 
Gut microbiota composition 
- 
Incidence of UTI 
- 
Antibiotic usage 
Population: 
Children born by Caesarean Section, aged between 6 
months and 3-years old 
No. of volunteers: 
Screen: n = 90 
Randomize: n = 60 (30 per group) 
Treatment: 
Lactobacillus paracasei N1115 versus placebo 
Duration/No. of visits: 
4 Visits (Screening, Weeks 0, 4 &8) 
Inclusion Criteria: 
To be eligible for inclusion, the subject must fulfill all of the 
following criteria: 
1. Male or female subjects aged ≥ 6 months and ≤ 3 years, 
2. Parent/Guardian has given written informed consent, 
3. Be in generally good health as determined by the 
investigator. 
Exclusion Criteria: 
The presence of any of the following criteria will exclude the 
subject from participating in the study: 
1. Are currently taking probiotics or prebiotics, or have taken 
them in the past 2 weeks, 
2. Unwilling to avoid probiotics / prebiotics for the duration of 
the study, 
3. Have a significant acute or chronic coexisting illness 
(cardiovascular, 
gastrointestinal, 
endocrinological, 
immunological, 
metabolic 
or 
any 
condition 
which 
contraindicates, in the investigators judgement, entry to 
the study), 
4. Having a condition or taking a medication that the 
investigator believes would interfere with the objectives of 
the study, pose a safety risk or confound the interpretation 

of the study results, 
5. Subjects have taken antibiotics within the past 3 months 
(history of antibiotic use in previous 6 months recorded), 
6. Subjects may not be receiving treatment involving 
experimental drugs, 
7. If the subject has been in a recent experimental trial, these 
must have been completed not less than 60 days prior to 
this study. 
Washout: 
14 days from probiotics & prebiotics 
Optional:  
daily eDiary: 
Parent/Guardian would be provided with a tablet PC and be 
instructed to record daily bowel frequency, stool consistency 
and GI symptoms (including flatulence, bloating, cramps) of 
their child. 
Parent/Guardian would complete the diary daily for the 2 
weeks prior to randomization and for the intervention period 
of 8-weeks.   
Analysis 
 Fecal microbiota 
 Fecal water metabolomics 
 Energy levels of infants-how to monitor it? 
 Level of antibiotic usage 
 Salivary cortisol 
 
2. STUDY PROCEDURES 
 
Study preparation:  
Design and compile case report form (CRF) and questionnaires. Site initiation visit and 
training of clinical staff on all aspects of the study will be performed. 
Subjects will be randomly assigned to placebo or study product and all study personnel 
and participants will remain blinded for the duration of the study.  
This study will be conducted in accordance with ICH GCP.  
 
 
 
 
The visit windows are set as outlined in the table & text below, but if exceptional 
circumstances occur then this window can be extended at the discretion of the Principal 
Investigator. To date there have been no visit window deviations. 
STUDY:  
Visit Number 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit   
Screening 
Week 0 Week4 
Week 8 
Window 
 -28 to -14 
days 
 
 
 
Informed Consent 
x 
Inc/Excl. 
x 
x 
Demographic data 
x 
Medical History 
x 
Anthropometric Measurements (Weight, 
x 
x 
x 
x 

height, BMI) 
Stool sample 
Saliva sample 
Randomization 
x 
Admin Study Product 
x 
x 
Return Product/Compliance 
x 
x 
Prior/con meds 
x 
x 
x 
x 
AE/SAE 
x 
x 
x 
Optional: 
Daily eDiary (electronic device to capture 
daily reports/symptoms) 
Stool Frequency, Consistency, GI 
Symptoms (including flatulence, bloating, 
cramps) 
 
Sample Collection & Processing:  
Stool Samples: Subjects are instructed to collect a stool sample before attending Visit 2, 
Visit 3 and Visit 4. Each parent/guardian is provided with a stool collection kit with two 
stool sample containers, and instructed to collect a sample the night before the visit, and 
again on the morning of the visit. If the child produces a sample on the morning of the visit, 
the sample collected the previous evening is discarded. Once the sample is delivered to 
the Atlantia clinic, it is placed in a refrigerator and collected by Teagasc. This collection 
occurs each day samples are delivered onsite by subjects. 
 
Saliva Samples: A saliva sample is collected from the subject during Visit 2, Visit 3 and 
Visit 4. The collection is carried out by a research nurse, who is trained according to 
Teagasc & Atlantia’s standard operating procedure for the collection of saliva. The saliva 
sample is collected by inserting a swab into the child’s mouth, letting it rest on the floor of 
the mouth for 30 seconds, allowing for soakage of any pooled saliva present. The swab is 
then rubbed on the child’s tongue, roof of mouth and left and right buccal mucosa for 10 
seconds each. Once collection has finished, the swab is placed into a vial and centrifuged 
at 1000g for 2 minutes. The separated saliva is aliquoted into a microtube and stored at 
-80℃. Once all subjects have completed the study and all samples have been collected, 
the samples will be shipped on dry ice for cortisol analysis. 
 
QC, Data-entry& statistical analysis:  
An independent study monitor will randomly review CRFs and source documentation to 
verify that the study is conducted in accordance with the protocol and GCP. After the last 
subject’s last visit all data from the CRFs will be independently entered, verified and 
corrected and statistical analysis will be performed. A draft report will be presented to the 
sponsor and upon required revisions, the final version will be completed.