Vitamin D Supplementation in Children With Sickle Cell Disease (VIDS)

Effect of Vitamin D Supplementation on Sickle Cell Disease Hospitalisation and Related Complications Among Children in Mulago Hospital: A Randomised Clinical Trial

Children aged 6 months to 12 years of age will be randomised to receive vitamin D 60,000IU once a month for 3 months or a placebo. The vitamin D will be in form of granules supplied in sachets. The primary study outcomes will be incidence of hospitalisation and change in vitamin D levels following supplementation. Secondary outcomes will include incidence of vaso-occlusive crisis (VOC), acute severe respiratory illness, Vitamin D related Severe adverse events and requirements for blood transfusion

Study Overview

• Status: Not yet recruiting
• Conditions: Children With Sickle Cell Disease at Mulago Hospital
• Intervention / Treatment: Dietary supplement: Vitamin D3

Detailed Description

BACKGROUND: More than 75% of all children with sickle cell anemia (SCA) are born in sub-Saharan Africa annually. The hallmark of SCA is haemolytic anaemia and or pain crisis that often require hospitalisation. Interventions to reduce the complications, which are prerequisites for frequent hospitalisations, are needed urgently. Vitamin D deficiency is common in children with SCA and is associated with recurrent vaso-occlusive crisis, blood transfusion, hospitalisation and infections. Routine vitamin D supplementation is not practiced in the care of sickle cell disease patients yet it has been associated with improved bone health and bone mineral density, reduced chronic pain and improved quality of life.

HYPOTHESIS: Vitamin D supplementation will lead to a lower incidence of hospitalisation than placebo in Ugandan children with SCA.

METHODS: The study will be a randomized, placebo-controlled, double blind clinical trial in which 331 Ugandan children with SCA aged 6 months to 12 years inclusive will receive vitamin D (60,000IU granules monthly) and another 331 a placebo (identical to vitaminD in appearance) for 3 months. The primary study outcome will be incidence of hospitalisation. Secondary outcomes will include incidence of vaso-occlusive crisis (VOC), acute severe respiratory illness, Vitamin D related Severe adverse events and requirements for blood transfusion IMPACT: If this trial shows a reduction in hospitalisation, it will be the basis for a multi-site pre-post intervention clinical trial to assess real-world safety and efficacy of Vitamin D in African children with SCA. The monthly administration is easy, and since vitamin D is inexpensive, this trial has the potential to improve the health of hundreds/ thousands of African children with SCA through reduction of infection-related morbidity and mortality.

• Study Type: Interventional
• Enrollment (Anticipated): 662
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Grace Ndeezi, PhD; Phone Number: +256 772453191; Email: gndeezi@gmail.com
• Study Contact Backup: Name: Ruth Namazzi, MMED; Phone Number: +256 772356331; Email: namazzi101@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Documented sickle cell disease (HbSS supported by hemoglobin electrophoresis results) attending Mulago Hospital Sickle Cell Clinic)
2. Age range of 6 months to 12 years, inclusive, at the time of enrolment
3. Weight at least 5.0 kg at the time of enrolment
4. Willingness to comply with all study-related treatments, evaluations, and follow-up

Exclusion Criteria:

1. Known other chronic medical condition (e.g., HIV, malignancy, Renal & liver disease, active clinical tuberculosis)
2. Severe acute malnutrition determined by impaired growth parameters as defined by WHO weight for length/height less than -3SD.
3. Evidence of Vitamin D supplementation in the past one month (by prescription or drug sample)

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
Active Comparator: Vitamin D supplement; 331 children will each received 60,000IU of vitamin D once a month for 3 months.	Dietary supplement: Vitamin D3; Vitamin D3 supplement
Active Comparator: Intervention; The intervention arm will receive vitamin D3.	Dietary supplement: Vitamin D3; Vitamin D3 supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of hospitalisation among children with SCD supplemented with vitamin D versus placebo.	Number of children hospitalised during the follow up period and number of hospitalisations per child	3 months follow up
Effect of vitamin supplementation on serum levels of 25 Hydroxyvitamin D levels in children with SCD	Serum levels of 25 Hydroxyvitamin D	3 months follow up
Frequency of blood transfusion among children supplemented with vitamin D versus Placebo in children with sickle cell anaemia	The number of children requiring blood transfusion during follow up and the episodes per child	3 months follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of vaso-occlusive crises (VOC)	Incidence of painful vaso-occlusive crises	3 months follow up
Incidence of acute severe respiratory illnesses	Incidence of cough associated with difficult breathing confirmed as pneumonia or acute chest syndrome by a health worker	3 months follow up
Severe adverse events	Serious adverse events for example severe diarrhoea and vomiting with dehydration.	3 months follow up

Collaborators and Investigators

• Sponsor: Makerere University
• Investigators: Principal Investigator: Grace Ndeezi, PhD, Makerere University, Kampala, Uganda

Publications and helpful links

General Publications

• Hyacinth HI, Gee BE, Hibbert JM. The Role of Nutrition in Sickle Cell Disease. Nutr Metab Insights. 2010 Jan 1;3:57-67. doi: 10.4137/NMI.S5048.
• Nolan VG, Nottage KA, Cole EW, Hankins JS, Gurney JG. Prevalence of vitamin D deficiency in sickle cell disease: a systematic review. PLoS One. 2015 Mar 3;10(3):e0119908. doi: 10.1371/journal.pone.0119908. eCollection 2015. Erratum In: PLoS One. 2015;10(5):e0128853.
• Dougherty KA, Schall JI, Bertolaso C, Smith-Whitley K, Stallings VA. Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children. J Pediatr Health Care. 2020 Sep-Oct;34(5):424-434. doi: 10.1016/j.pedhc.2020.04.007. Epub 2020 Jun 5.
• Ndeezi G, Kiyaga C, Hernandez AG, Munube D, Howard TA, Ssewanyana I, Nsungwa J, Kiguli S, Ndugwa CM, Ware RE, Aceng JR. Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study. Lancet Glob Health. 2016 Mar;4(3):e195-200. doi: 10.1016/S2214-109X(15)00288-0. Epub 2016 Jan 29.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 17, 2021
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): January 31, 2022

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2020-117

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant information may be shared with other researchers.
• IPD Sharing Time Frame: within one year and the sharing period could extend beyond this period
• IPD Sharing Access Criteria: If requested by other researchers who have carried out similar studies for a meta-analysis
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

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