the Effect of High Caloric Oral Nutritional Supplements on Growth and Development of Malnourished Children (EHCONSGDMC)

The goal of this clinical trial is to investigate the effect of high caloric oral nutritional supplements on body proportion, weight, linear growth pattern, neuropsychological development level and related health aspects (gut health, immune function, quality of life, etc.) in participants aged 1 to 3 years who are malnourished (underweight and wasting),as well as to evaluate the safety of applying high caloric oral nutritional supplements. Participants will receive nutritional education and daily high caloric oral nutritional supplements(experimental group),or will receive nutritional education and dietary instruction(control group).This study may provide data to support the development of clinical intervention strategies for malnourished Chinese children.

Study Overview

• Status: Not yet recruiting
• Conditions: Malnutrition, Child; Nutritional Deficiency; Malnourishment; Undernutrition
• Intervention / Treatment: Dietary supplement: high caloric oral nutritional supplements; Behavioral: nutritional education; Behavioral: dietary guidance

Detailed Description

Background:Growth and development is an important indicator of children's health and nutritional status, and nutrition is the most important material basis for growth and development. The prevention and treatment of malnutrition in children can be achieved by choosing whole nutritional formulas for special medical purposes as oral nutritional supplements (ONS), which has been confirmed by some overseas clinical studies to promote the growth benefit of malnourished children, but no multicenter clinical study has been conducted in China on the effect of ONS on the improvement of growth and development of malnourished Chinese children.

Objective and significance: To investigate the effects of high caloric ONS on body proportion, weight, linear growth pattern, neuropsychological development level and related health aspects (gut health, immune function, quality of life, etc.) in children, as well as to evaluate the safety of applying high caloric ONS, and to provide data to support the development of clinical intervention strategies for malnourished Chinese children.

Research design:A multicenter, randomized, controlled clinical trial design method is used to randomize children who meet the inclusion criteria into the experimental and control groups using a competitive entry method. The test group is given nutritional education and high caloric ONS (which can supplement 30% of the energy requirement), while the control group is given nutritional education and dietary instruction.Participants are followed up at 0, 1,2, 3, 6, and 12 months of enrollment. The investigators will collect dietary diaries, physical indicators, developmental quotient scores, quality of life measures, gut health, infectious disease-related questionnaires and safety indicators (blood biochemical indicators, urine routine) from children in both groups to comprehensively assess the effect of high caloric ONS intervention on physical growth, neuropsychological development levels and related aspects (gut health, immune function, quality of life, etc.) of malnourished children, as well as to conduct safety analyses.

Sample size:According to similar studies to date, a total of 800 people are recommended for this study.

Statistical analysis: Statistical analysis is performed using SAS 9.4. For continuous variables (height, weight, BMI-Z score, DQ score, etc.), statistical descriptions are performed using mean and standard deviation (conforming to normal distribution) or median and interquartile range (IQR); for categorical variables, statistical descriptions are performed using frequency and percentage; for the main efficacy indicators, mixed-effects models are used for efficacy evaluation indicators according to the principle of adjusted intentionality analysis (mITT). For the safety evaluation, the number, frequency and incidence of adverse events and reactions are calculated, and the positive abnormal changes of laboratory biochemical indexes such as blood routine, urine routine, liver and kidney function are counted. p value < 0.05 is considered statistically significant.

Ethical matters and data protection: The guardians of the children participating in the study will sign an informed consent form. This study is approved by the local ethics committee. Patients' names will be abbreviated and study data will be assigned a code which will then be provided to the investigator. Parental authorization for patient health information will remain in effect until the study is completed. After that, private information will be removed from the study records by the researcher.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Li Chen, doctor; Phone Number: +86 136 7762 0103; Email: chenli2012@126.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Children's Hospital
      • Contact: Ya Wang, master's degree; Phone Number: +86 13855150595; Email: 22891588@qq.com
  • Beijing
    • Beijing, Beijing, China, 100020
      • Children's Hospital of The Capital Institute of Pediatrics
      • Contact: Lin Wang, MD; Phone Number: +86 13501362346; Email: caroldoctor@126.com
  • Chongqing
    • Chongqing, Chongqing, China, 400014
      • Growth, Development and Mental health of Children and Adolescence Center
      • Contact: Li Chen, MD; Phone Number: +86 (+86)136 7762 0103; Email: chenli2012@126.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510200
      • Guangzhou Women and Children's Medical Center
      • Contact: Yan Hu, master's degree; Phone Number: +86 13560366657; Email: yayayan1979@163.com
  • Guizhou
    • Guiyang, Guizhou, China, 550003
      • Guiyang Maternity and Child Health Care Hospital
      • Contact: Yan Luo, MD; Phone Number: +86 18585011079; Email: 718410342@qq.com
  • Hunan
    • Changsha, Hunan, China, 410007
      • Hunan Children's Hospital
      • Contact: Yan Zhong, bachelor's degree; Phone Number: +86 13873170189; Email: zhongyan@163.com
  • Jiangsu
    • Nanjing, Jiangsu, China, 210004
      • Nanjing Maternity and Child Health Care Hospital
      • Contact: Xia Chi, MD; Phone Number: +86 13813875862; Email: 264601855@qq.com
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Maternal and Child Health Hospital
      • Contact: Ping Xu, bachelor's degree; Phone Number: +86 13879112716; Email: 278938835@qq.com
  • Shanxi
    • Baoji, Shanxi, China, 721000
      • Baoji Maternity and Child Healthcare Hospital
      • Contact: Xueqin Li, master's degree; Phone Number: +86 15229681332; Email: 85581703@qq.com
    • Xianyang, Shanxi, China, 712000
      • Xianyang Children's Hospital
      • Contact: Hongxia Yan, bachelor's degree; Phone Number: +86 15909263117; Email: 1142179306@qq.com
  • Sichuan
    • Chengdu, Sichuan, China, 610091
      • Chengdu Women's and Children's Central Hospital，School of Medicine，University of Electronic Science and Technology of China
      • Contact: Lan Zhang, master's degree; Phone Number: +86 13982156971; Email: 893279990@qq.com
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Kunming Children's Hospital
      • Contact: Yu Ling, bachelor's degree; Phone Number: +86 13888594860; Email: lingyu@etyy.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 1-3 years
• BMI for Age Z-score<-2
• Height-for-age z score<-2
• Total daily energy intake<75% of recommended nutrient intake
• The child's guardian is willing to participate in this study and sign an informed consent form.

Exclusion Criteria:

• Chronic or severe infectious disease (e.g., chronic hepatitis, HIV or tuberculosis infection)
• Certain congenital or genetic diseases affecting physical growth and development (congenital heart disease, Down's syndrome, infantile anorexia nervosa, etc.), malignancies and use of drugs (diuretics, appetite stimulants, steroids and growth hormones, etc.)
• Severe gastrointestinal disorders (e.g., celiac disease, short bowel syndrome, inflammatory bowel disease, etc.)
• Acute and chronic respiratory/digestive tract infections within 2 weeks prior to enrollment
• Allergy or contraindication to any of the ingredients in the high-energy total nutrition formula used in this study
• Have used high-energy enteral nutrition preparations for the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high caloric oral nutritional supplements group; Participants aged 1 to 3 years who are malnourished (underweight and wasting). They will receive nutritional education,dietary instruction and daily high caloric oral nutritional supplements for 12 months.	Dietary supplement: high caloric oral nutritional supplements; High caloric oral nutritional supplements (which can supplement 30% of the energy requirement) is given daily, and the recommended amount of energy and protein is referred to the 2013 Chinese Dietary Nutrient Reference Intake Table. At 6 months of enrollment, participants will be asked to evaluate whether to continue feeding according to the experimental group protocol or to stop to ensure proper nutritional intake.; Other Names: high-energy total nutrition formula; Behavioral: nutritional education; After enrollment,health education information is pushed approximately every 4 weeks through the WeChat platform or/and short text messages to parents.; Behavioral: dietary guidance; At follow-up visits at 0, 1, 2, 3, 6,and 12 months after enrollment, a professionally trained pediatrician give the participant's guardian dietary instructions appropriate to the age stage and physical condition of the child. Each session lasts approximately 10 minutes.
Active Comparator: nutritional education and dietary guidance group; Participants aged 1 to 3 years who are malnourished (underweight and wasting). They will receive nutrition education and dietary instruction.	Behavioral: nutritional education; After enrollment,health education information is pushed approximately every 4 weeks through the WeChat platform or/and short text messages to parents.; Behavioral: dietary guidance; At follow-up visits at 0, 1, 2, 3, 6,and 12 months after enrollment, a professionally trained pediatrician give the participant's guardian dietary instructions appropriate to the age stage and physical condition of the child. Each session lasts approximately 10 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI for Age Z-score(BAZ)	Trained research assistants or health care practitioners obtain weight in kilograms and height in centimeters (mean of 3 consecutive measurements). Height and weight will be combined to report BMI in kg/m^2.Then, the BAZ is calculated using WHO2011v3.2.2 software.	at 6 months of enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dietary Diary	Participants provide a dietary diary over an average two-day period through a WeChat app each visit. The app prompts participants to record and estimate details of all meals and snacks they consumed, especially formula used in the study.	at 0, 1, 2, 3, 6 and 12 months of enrollment
BMI for Age Z-score(BAZ)	Trained research assistants or health care practitioners obtain weight in kilograms and height in centimeters (mean of 3 consecutive measurements). Height and weight will be combined to report BMI in kg/m^2.Then, the BAZ is calculated using WHO2011v3.2.2 software.	at 0, 1, 2, 3 and 12 months of enrollment
Weight for Age Z-score(WAZ)	Trained research assistants or health care practitioners obtain weight in kilograms using a standardized approach. Weight is measured using a precision digital scale or mechanical scale(mean of 3 consecutive measurements). Then, the WAZ is calculated using WHO2011v3.2.2 software.	at 0, 1, 2, 3, 6 and 12 months of enrollment
Height for Age Z-score(HAZ)	Trained research assistants or health care practitioners obtain height in centimeters using a standardized approach. Height is measured with a calibrated stadiometer(mean of 3 consecutive measurements). Then, the HAZ is calculated using WHO2011v3.2.2 software.	at 0, 1, 2, 3, 6 and 12 months of enrollment
Gesell Developmental Scale Test	Mainly assesses participants in 5 areas:adaptive behavior, gross motor, fine motor, language behavior,personal-social behavior, the evaluation finally calculates the developmental quotient (DQ) of each area. Diagnostic criteria: DQ is more than or equal to 86 is normal, DQ is marginal between 76 and 85, DQ is mild mental retardation between 55 and 75, DQ is moderate mental retardation between 40 and 54, DQ is severe mental retardation between 25 and 39, and DQ is less than or equal to 25 is extremely severe mental retardation.	at 0, 6, and 12 months of enrollment
Infants - Junior High School Students Social Competence Test (S-M test)	The scale, derived from the revised version of the Japanese Social Competence test (S-M test) and revised by a Chinese researcher, is applicable to children from 6 months of age to 14 years of age and includes 132 items in 6 sections with 7 starting ages, which are filled in item by item by parents or daily caregivers according to the appropriate age, with ≥10 being normal.	at 0, 6, and 12 months of enrollment
Pediatric Quality of Life Inventory (PedsQL)	The quality of life of the participants is assessed using the Pediatric Quality of Life Inventory.The Infant Scale or Generic Core Scales is completed according to age.Scores are transformed on a scale from 0 to 100,with higher scores indicating better quality of life.	at 0, 6, and 12 months of enrollment
the Chinese version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF)	The quality of life of parents is assessed using the WHOQOL-BREF.The WHOQOL-BREF, comprises 26 items, two general items and 24 others, across the following four domains: physical (7 items), psychological (6 items), social (3 items), and environmental (8 items).Calculate the average score of all items in each domain, converted into a score of 4 to 20 or 0 to100 by two algorithms,with higher scores indicating better quality of life.	at 0, 6 and 12 months of enrollment
Gut Health Questionnaire	A questionnaire is used to understand gut health, including entries on the Bristol Stool Scale (to assess stool status), the average number of bowel movements per day, and the frequency of bloating and abdominal pain.	at 0, 1，3, 6, and 12 months of enrollment
Infectious Diseases Related Questionnaire	A infectious disease-related questionnaire is used to understand immune function, including the number and duration of upper respiratory tract infections, infectious diarrhea.	at 0, 1，3, 6, and 12 months of enrollment
Blood Routine Test	Blood routine test is completed at 0, 6 and 12 months of enrollment for safety analysis.Includes the following parameters:white blood cell count,red blood cell count,hemoglobin,mean corpuscular hemoglobin concentration,platelet,standard deviation in red cell distribution width,coefficient variation of red blood cell volume distribution width,platelet distribution width,mean platelet volume,platelet larger cell ratio,thrombocytocrit,neutrophil ratio,lymphocyte ratio,monocyte ratio,eosinophil ratio,basophil ratio,neutrophil count,lymphocyte count,monocyte count,eosinophil count,basophil count.	at 0, 6 and 12 months of enrollment
Liver Function Test	Liver function test is completed at 0, 6 and 12 months of enrollment for safety analysis.Includes the following parameters:total protein,albumin,globulin,alanineamino transferase,aspartate amino transferase,bilirubin,direct bilirubin,total bile acid,alkaline phosphatase,amma-glutamyl transpeptidase.	at 0, 6 and 12 months of enrollment
Renal Function Test	Renal function test is completed at 0, 6 and 12 months of enrollment for safety analysis.Includes the following parameters:creatinine,blood urea nitrogen.	at 0, 6 and 12 months of enrollment
Urine Routine Test	Urine routine test is completed at 0, 6 and 12 months of enrollment for safety analysis.Includes the following parameters:urinary bilirubin,urinary ketone bodies,blood,urinary white blood cells,urinary red blood cells,urinary sugar,urinary protein,urinary cast.	at 0, 6 and 12 months of enrollment

Collaborators and Investigators

• Sponsor: Children's Hospital of Chongqing Medical University
• Collaborators: Chengdu Women's and Children's Central Hospital; Kunming Children's Hospital; Nestle Health Science; Nanjing Maternity and Child Health Care Hospital; Hunan Children's Hospital; Guangzhou Women and Children's Medical Center; Jiangxi Maternal and Child Health Hospital; Xianyang Children's Hospital; Children's Hospital of The Capital Institute of Pediatrics; Anhui Provincial Children's Hospital; Guiyang Maternity and Child Health Care Hospital; Baoji Maternity and Child Healthcare Hospital
• Investigators: Study Director: Li Chen, doctor, Children's hospital of Chongqing Medical University

Publications and helpful links

General Publications

• Hemming K, Taljaard M, McKenzie JE, Hooper R, Copas A, Thompson JA, Dixon-Woods M, Aldcroft A, Doussau A, Grayling M, Kristunas C, Goldstein CE, Campbell MK, Girling A, Eldridge S, Campbell MJ, Lilford RJ, Weijer C, Forbes AB, Grimshaw JM. Reporting of stepped wedge cluster randomised trials: extension of the CONSORT 2010 statement with explanation and elaboration. BMJ. 2018 Nov 9;363:k1614. doi: 10.1136/bmj.k1614.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2023
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: June 16, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Oral Nutritional Supplements; Neuropsychological Development; Physique Growth
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Child Nutrition Disorders
• Other Study ID Numbers: EHCONSGDMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data is confidential during the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No