Severe Acute Malnutrition
Conditions
Brief summary
This double-blind randomized placebo-controlled controlled trial will test the hypothesis that administration of high-dose oral vitamin D supplementation to children in Lahore, Pakistan, who are recovering from complicated severe acute malnutrition will safely accelerate weight gain (primary outcome) and enhance neurodevelopment, muscle mass accumulation, resolution of systemic inflammation and antimicrobial immune function (secondary outcomes).
Interventions
DIETARY_SUPPLEMENTVitamin D3
ATC code A11CC05 (cholecalciferol)
DIETARY_SUPPLEMENTPlacebo
Ethyl oleate
Sponsors
University of the Punjab
University College, London
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 5 Years
Healthy volunteers
No
Inclusion criteria
* Consent of parent / guardian * Age 6-59 months at enrolment * Diagnosis of complicated SAM at the point of hospital admission as defined by the World Health Organisation. * Medical team managing the child has made the decision to discharge the child from inpatient care
Exclusion criteria
* Ingestion of a dose of vitamin D\>200,000 IU (5 mg) in the last 3 months * Known diagnosis of primary hyperparathyroidism or sarcoidosis (i.e. conditions pre-disposing to vitamin D hypersensitivity) * Known neurodevelopmental disorder (e.g. cerebral palsy) * HIV infection * Taking anti-tuberculosis treatment * Inability to assess child's developmental status at baseline using the Malawi Development Assessment Tool * Signs of rickets * Corrected serum calcium concentration \>2.65 mmol/L on blood sample taken during the current hospital admission
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean weight-for-height/length z-score | 2 months |
Secondary
| Measure | Time frame |
|---|---|
| Mean mid-upper arm circumference | 2 and 6 months |
| Mean weight-for-height/length z-score | 6 months |
| Mean weight-for-age z-score | 2 and 6 months |
| Mean height/length-for-age z-score | 2 and 6 months |
| Mean change in overall and domain-specific (gross motor, fine motor, language and social) neurodevelopmental scores, Malawi Developmental Assessment Tool | 2 and 6 months |
| Mean fat mass index | 2 and 6 months |
| Mean fat-free mass index | 2 and 6 months |
| Proportion of participants experiencing relapse of severe acute malnutrition | 6 months |
| Proportion of participants readmitted to hospital due to any cause | 6 months |
| Antimicrobial immune function (concentrations of inflammatory mediators in supernatants of whole blood stimulated with lipo-polysaccharide, zymosan and heat-killed Salmonella typhi) | 2 and 6 months |
| Serum concentrations of albumin, C-reactive protein, 25-hydroxyvitamin D, total alkaline phosphatase, parathyroid hormone, ferritin and hepcidin | 2 and 6 months |
| Mean head circumference-for-age z-score | 2 and 6 months |
| Mean corpuscular volume, full blood count | 2 and 6 months |
| Mean corpuscular haemoglobin concentration, full blood count | 2 and 6 months |
| Mean neutrophil count, full blood count | 2 and 6 months |
| Mean lymphocyte count, full blood count | 2 and 6 months |
| Mean monocyte count, full blood count | 2 and 6 months |
| Faecal concentrations of inflammatory markers (myeloperoxidase, neopterin and alpha-1 antitrypsin) | 2 and 6 months |
| Faecal microbiome composition | 2 and 6 months |
| Proportion of participants dying | 6 months |
| Incidence of serious adverse events | 6 months |
| Incidence of adverse reactions | 6 months |
| Mean haemoglobin concentration, full blood count | 2 and 6 months |
Countries
Pakistan
Outcome results
None listed