Post Discharge Trial to Enhance Immunity in Severely Malnourished Children

Enhancing Immunity and Nutrition in Severely Malnourished Children Following Hospital Discharge: a Two Arm Open-label Randomized Controlled Trial of Microbiota-Directed Food vs. Zinc With Micronutrient Powder and Khichuri

The goal of this study is to evaluate the efficacy of microbiota-directed food in comparison to zinc with micronutrient powder and Khichuri on changes in circulating immune cells (monocytes, T cells, B cells, and NK cells) in malnourished children after recovery from acute infection.

The study aims to answer the research question:

Does microbiota-directed food (MDF) compared to zinc with micronutrient powder (MNP) and Khichuri therapy enhance immunity in children with severe acute malnutrition? The researcher will compare the effectiveness of microbiota-directed food (MDF) versus zinc with micronutrient powder (MNP) and Khichuri therapy to see if MDF enhances immunity in severely malnourished children.

Severely malnourished children will:

• Receive microbiota-directed food (MDF) or zinc with micronutrient powder (MNP) and Khichuri every day for 12 weeks.
• Phenotyping of circulating immune cells (NK cells, T cells, B cells) will be conducted using flow cytometry and fluorescence-activated cell sorting techniques.

Study Overview

• Status: Not yet recruiting
• Conditions: Child Malnutrition
• Intervention / Treatment: Dietary supplement: Microbiota-directed food; Dietary supplement: Khichuri

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Farzana Afroze, MBBS, FCPS; Phone Number: +8801722363067; Email: farzana9afroze9@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Children aged 6 months to 36 months, and
• Severe acute malnutrition as evident by weight-for-length z-score (WLZ) < -3 and or mid-upper arm circumference (MUAC) < 11.5 cm, and or edema of both feet, and
• Completed the acute phase management for SAM and stayed at NRU for 7±4 days, with no medical complications, e.g. lethargic/unconscious, convulsions, unable to drink, persistent vomiting, respiratory distress.
• Residing within the Dhaka district.
• Parents/guardians provided written informed consent.

Exclusion Criteria:

• WLZ ≥ -3 or MUAC ≥11.5 cm.
• Presence of lethargy/unconsciousness, convulsions, unable to drink, persistent vomiting, respiratory distress.
• Participants who receive multiple courses of antibiotic (>2 courses during acute phase) treatment for a prolonged period (>14 days).
• Persistent diarrhea (≥14 days).
• Chronic illness or disability affecting food intake, e.g. TB, HIV, congenital defects, cerebral palsy
• Treated for SAM in the previous 3 months.
• Known case of soy, peanut, or milk protein allergy.
• Any sibling of the enrolled child.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microbiota-directed food; Children randomized to this group will receive Microbiota-directed food (MDF) daily for 12 weeks. MDF can modulate the gut microbiota and enhance host immunity, growth, and development in malnourished children.	Dietary supplement: Microbiota-directed food; MDF can modulate the gut microbiota and enhance host immunity, growth, and development in malnourished children. Each sachet of MDF (100 gm) provides approximately 500 kcal.; Other Names: MDF
Active Comparator: Khichuri; Children randomized to this group will receive zinc with Micronutrient powder (MNP) and Khichuri daily for 12 weeks.	Dietary supplement: Khichuri; Khichuri is a home-based nutritious food with high energy and protein. This arm also contains zinc (10 gm/day), micronutrient powder, and an egg daily.; Other Names: Locally available food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NK cells	Differences in the proportion and activity of circulating NK cells between the groups 12 weeks after the intervention, measured by flow cytometry/fluorescence-assisted cell sorter (FACS).	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating immune cells	Differences in the proportion of circulating immune cells (NK cells, T cells, B cells) before and after the interventions	12 weeks
Cytokines and chemokines	Differences in the levels of pro-inflammatory and anti-inflammatory cytokines and chemokines in circulation, which can provide insights into the functional status of immune cells	12 weeks
Micro biocidal capacity	Differences in the micro biocidal capacity (oxidative burst) of neutrophils and monocytes.	12 weeks
Rate of weight gain	Rate of weight gain between the intervention groups over the 12-weeek intervention period.	12 weeks
Diarrhea and pneumonia	Incidence of acute diarrhea and pneumonia during the study period.	12 weeks
Gut microbiota	Composition and evolution of gut microbiota over the 12-weeek intervention period.	12 weeks
Case fatality rate	Case fatality rate within 12 weeks post discharge.	12 weeks
Anthropometric recovery	Anthropometric recovery from SAM: anthropometric recovery will be defined as reaching a WLZ of >-2 (for those admitted with WLZ <-2) and or MUAC >12.5 (for those admitted with MUAC <12.5 cm).	12 weeks

Collaborators and Investigators

• Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
• Collaborators: Washington University School of Medicine
• Investigators: Principal Investigator: Farzana Afroze, International Centre for Diarrhoeal Disease Research, Bangladesh

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 28, 2024
• First Submitted That Met QC Criteria: July 28, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Immunity; Gut microbiota; Malnutrition; Zinc; NK cells; Microbiota-directed food (MDF)
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Child Nutrition Disorders
• Other Study ID Numbers: PR-24010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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