Clinical trial NCT05044910: The Impact of Malnutrition on Immune Responses to Tuberculosis
Official title: The Impact of Malnutrition on Immune Responses to Tuberculosis in Indian Children
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Malnutrition, Child
Tuberculosis
Keywords: malnutrition
moderate acute malnutrition
immunology
Lead sponsor: Tuberculosis Research Centre, India
Sponsor class: OTHER_GOV
Collaborators: name: Institute of Child Health, Madras Medical College, Chennai
name: Stanley Medical College
name: Kanchi Kamakoti Childs Trust Hospital, Chennai, India
name: Queen Mary University of London
name: London School of Hygiene and Tropical Medicine
name: DBT, India
First posted: 2021-09-16
Enrollment: 200
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV negative, BCG vaccinated

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

Eligibility criteria: 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

Primary outcomes:
measure: IFNγ concentration
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chennai
country: India
facility: Institute of Child Health
state: Tamil Nadu
city: Chennai
country: India
facility: Government Stanley Medical College and Hospital
state: Tamil Nadu
Study officials:
affiliation: ICMR-NIRT
name: Aishwarya Venkataraman, MRCPCH
role: PRINCIPAL_INVESTIGATOR
References: