Overview
The goal of this clinical trial is to learn if a high-energy liquid diet improves the nutritional status of children with chronic cholestasis (a liver condition that blocks bile flow). Researchers want to see if this diet helps children who are malnourished.
The main questions the study aims to answer are:
- Does the liquid diet raise the level of prealbumin (a marker of nutrition) in the blood?
- Does the liquid diet raise the level of Insulin-like Growth Factor-1 (IGF-1) (a hormone that helps growth) in the blood?
Participants will:
- Consume a high-energy liquid diet for 14 days.
- Give blood samples at the start and at the end of the 2-week study.
- Keep a daily record of what they eat and drink in a food diary. Researchers will compare the blood test results from the start and the end of the study to see if the liquid diet works to improve the children's prealbumin and IGF-1 levels. This study is important to help children with liver problems grow better and stay healthy.
Description
The study evaluates the effect of nutritional therapy on prealbumin levels and insulin-like growth factor-1 (IGF-1) levels in malnourished children with chronic cholestasis aged 3-59 months (primary outcome) and diet tolerance, nutritional status, and medical condition (secondary outcomes).
Prealbumin and IGF-1 levels are measured as primary outcomes at baseline (day 0) and at day 15. Diet tolerance is assessed using the Bristol Stool Chart, a daily vomiting record throughout the 14-day intervention period, and allergic reactions. The frequency of defecation and consistency of each stool are documented. Allergic reactions are also monitored during the intervention period, including symptoms such as fever, erythematous rash, pruritus, and respiratory symptoms such as shortness of breath. The onset, duration, and severity of these symptoms are recorded.
Vomiting is evaluated as the number of episodes per day over the 14-day intervention period, and the volume of each episode is recorded. Only vomiting attributable to diet intolerance is included in the analysis, while episodes related to other causes, such as coughing or crying, are excluded.
Anthropometric parameters, including weight, height, mid-upper arm circumference, and other relevant measurements, are assessed on day 0, day 8, and day 15 to monitor changes in nutritional status.
Medical conditions during the study period are closely monitored, including underlying diseases, comorbidities, and intercurrent illnesses (e.g., respiratory or gastrointestinal infections). Clinical changes, hospitalizations, medication use, and any complications occurring during the intervention are recorded to evaluate their potential impact on nutritional status and study outcomes.
Nutritional therapy is administered as a liquid diet providing 130% of the recommended daily allowance (RDA), with macronutrient and micronutrient composition adjusted according to the 2019 ESPGHAN and 2021 Tessitore guidelines, over a 14-day intervention period. To ensure accurate nutritional intake, feeding is administered via a nasogastric tube, with gradual advancement of caloric intake until reaching 130% of RDA by day 4. Feeding is performed by parents or caregivers who are trained in proper administration techniques, feeding schedules, and hygiene practices. Monitoring of dietary adherence is conducted by daily food recall, instant messaging, and video call supervision during feeding sessions.
Protocol for nutritional therapy advancement is as follows:
- Calorie requirement is calculated by multiplying ideal body weight with daily energy requirement (recommended dietary allowance, RDA).
- Ideal body weight is defined as the median weight for actual height based on WHO growth charts (weight-for-height/length).
- Height age is defined as the median age corresponding to the patient's actual height based on WHO growth charts (height/length-for-age).
- The target energy intake is set at 130% of RDA according to height age, in line with ESPGHAN 2019 and Tessitore 2021 recommendations.
- On the first day: patients are provided with 44 to 140 more calories than their usual daily intake, based on the results of a food recall analysis. Nutritional therapy is administered as a liquid diet via a nasogastric tube, divided into 8 feeding sessions per day (every 3 hours).
- On the second day to fourth day: caloric intake is gradually increased until reaching 130% of RDA on the fourth day. The feeding regimen (volume and frequency) is adjusted according to patient tolerance.
- From fourth day to fourteenth day: the patient is maintained on full nutritional therapy at 130% of RDA. Monitoring of intake is conducted through daily food recall and communication via instant messaging/video calls.
Adjustments to feeding (volume, frequency, or rate) are made based on diet tolerance. If gastrointestinal intolerance or metabolic complications occur, nutritional therapy is modified according to clinical guidelines.
Eligibility
Inclusion Criteria:
- Children under 5 years old
- Diagnosed with chronic cholestasis and severe malnutrition
- Parental/guardian informed consent
- Willingness to use a nasogastric tube (NGT) if indicated
- Covered by national health insurance or other insurance
Exclusion Criteria:
- Comorbidities (heart failure, chronic kidney disease, HIV)
- Severe acute infections (acute gastroenteritis, dengue fever, pneumonia)
- Post-liver transplant
- Post-Kasai portoenterostomy (jaundice-free)
- Currently exclusively breastfeeding
- Use of steroids or NSAIDs within two weeks prior to the study.
- Receiving a transfusion of whole blood, fresh frozen plasma, or platelets within one week prior to the study
