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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Severe Acute Malnutrition
• Intervention / Treatment: Dietary supplement: Vitamin D3; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Adrian R Martineau, MD PhD; Phone Number: +442078822511; Email: a.martineau@qmul.ac.uk
• Study Contact Backup: Name: Javeria Saleem, MD PhD; Email: javeria.hasan@hotmail.com

Study Locations

• Pakistan
  • Lahore, Pakistan
    • Sir Ganga Ram Hospital
  • Lahore, Pakistan
    • THQ Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D; 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; ATC code A11CC05 (cholecalciferol)
Placebo Comparator: Placebo; Two oral doses of 1 ml ethyl oleate	Dietary supplement: Placebo; Ethyl oleate

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: University College, London; University of the Punjab

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 7, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition; Severe Acute Malnutrition; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: ViDiSAM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified IPD will be shared with other researchers subject to terms of Data Transfer Agreement and IRB approval
• IPD Sharing Time Frame: 2 years after completion of the trial
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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