Trial of High-Dose Vitamin D in the Treatment of Complicated Severe Acute Malnutrition

Study Overview
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Brief Summary
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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).

Official Title
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Trial of High-Dose Vitamin D in the Treatment of Complicated Severe Acute Malnutrition

Conditions
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Severe Acute Malnutrition

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D<br>Two oral doses of 5 mg (200,000 international units) vitamin D3 in 1 ml ethyl oleate, given at baseline and two weeks thereafter | Dietary Supplement: Vitamin D3<br>* ATC code A11CC05 (cholecalciferol)<br>|
| Placebo Comparator: Placebo<br>Two oral doses of 1 ml ethyl oleate | Dietary Supplement: Placebo<br>* Ethyl oleate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean weight-for-height/length z-score |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 head circumference-for-age z-score |  | 2 and 6 months | 
| Mean mid-upper arm circumference |  | 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 haemoglobin concentration, full blood count |  | 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 |