The Impact of Malnutrition on Immune Responses to Tuberculosis

Active, not recruiting

• Conditions: Malnutrition, Child; Tuberculosis
• Interventions: Dietary Supplement: Ready to Use supplementary food (RUSF)

• Registration Number: NCT05044910
• Lead Sponsor: Tuberculosis Research Centre, India

Brief Summary

The aim of this study is to assess immune responses to Mtb in children with MAM compared to well-nourished children and to evaluate the impact of a nutrition intervention on these immune responses.

Detailed Description

Immune dysfunction in malnourished children is poorly characterised. The aim of this study is to assess immune responses to Mycobacterium tuberculosis (Mtb) in children with moderate acute malnutrition (MAM) compared to wellnourished children and to evaluate the impact of a nutrition intervention on these immune responses. Innate and adaptive immune responses to Mtb will be characterised in four groups: 1) MAM children with TB disease; 2) Wellnourished children with TB disease; 3) MAM children with latent TB infection; 4) Well-nourished children with latent TB infection. A range of assays to compare innate, adaptive and functional immune responses to TB between groups will be performed. Whether nutritional supplementation improves immune function in MAM children remains uncertain. Hence, children in all four groups will be followed up during 6 months of TB therapy/chemoprophylaxis. MAM children will receive 12 weeks of concomitant ready-to-use supplementary food, to evaluate longitudinal changes in innate and adaptive immune function, monocyte:lymphocyte ratio and mycobacterial growth inhibition. The results of this study will provide data to understand the reasons for infection susceptibility in malnourished children and provide a proof-of-concept that nutritional rehabilitation promotes immune rehabilitation. It will also provide a proof-of concept for use of nutritional supplementation as adjust therapy in TB disease

Study Timeline

• Study Start: 2020-08-01
• Study First Submitted: 2021-09-09
• Study First Submitted QC: 2021-09-09
• Study First Posted: 2021-09-16
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-26
• Last Update Posted: 2024-05-29
• Primary Completion: 2024-08-31
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Age 12-60 months
• HIV-negative
• BCG vaccinated
• Moderate acute malnutrition (WHZ -2 to -3 or MUAC 115 - 125mm ± HAZ <-2)
• TB disease
• Latent TB infection

Exclusion Criteria

• Inclusion criteria not met
• Severe acute malnutrition (WHZ<-3; MUAC<115mm; bilateral oedema)
• Severe anaemia (Hb: <7g/dl)
• Chronic infection (HIV, hepatitis B or C)
• Chronic disease (e.g. Crohn's disease)
• Feeding problems (eg cerebral palsy) that prevent ingestion of RUSF
• Known nut allergy
• MDR TB disease and contacts of MDR TB adults

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MAM children with TB disease	Ready to Use supplementary food (RUSF)	-
MAM children with latent TB infection	Ready to Use supplementary food (RUSF)	-

Primary Outcome Measures

Name	Time	Method
IFNγ concentration	6 months	IFNγ concentration in supernatant after overnight incubation of whole blood with TB antigens

Trial Locations

Locations (2)

Institute of Child Health; 🇮🇳 Chennai, Tamil Nadu, India

Government Stanley Medical College and Hospital; 🇮🇳 Chennai, Tamil Nadu, India