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

• ClinicalTrials.gov Identifier: NCT04662476
• Recruitment Status: Unknown
• First Posted: December 10, 2020
• Last Update Posted: April 13, 2021
• Sponsor: Makerere University
• Information provided by (Responsible Party): College of Health Sciences, Makerere University

Tracking Information

• First Submitted Date: December 4, 2020
• First Posted Date: December 10, 2020
• Last Update Posted Date: April 13, 2021
• Estimated Study Start Date: May 17, 2021
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 9, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 9, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vitamin D Supplementation in Children With Sickle Cell Disease
• Official Title: Effect of Vitamin D Supplementation on Sickle Cell Disease Hospitalisation and Related Complications Among Children in Mulago Hospital: A Randomised Clinical Trial
• Brief Summary: 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

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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

331 children will be randomised to the intervention and another 331 to the placebo.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The sachets containing vitamin D will be exactly similar to the ones containing the placebo. Both the intervention and placebo granules will be identical in colour, odour, taste and amount. Children will be randomized into treatment groups by order of entry in the study, based on a pre-determined blinded randomization list created and managed by an independent statistician.

Primary Purpose: Treatment

• Condition: Children With Sickle Cell Disease at Mulago Hospital

Intervention

Dietary Supplement: Vitamin D3

Vitamin D3 supplement

Study Arms

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

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 9, 2020): 662
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2022
• Estimated Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 12 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04662476
• Other Study ID Numbers: 2020-117
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified participant information may be shared with other researchers.
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: within one year and the sharing period could extend beyond this period
• Access Criteria: If requested by other researchers who have carried out similar studies for a meta-analysis

• Current Responsible Party: College of Health Sciences, Makerere University
• Original Responsible Party: College of Health Sciences, Makerere University, Makerere College of Health Sciences
• Current Study Sponsor: Makerere University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Makerere University
• Verification Date: April 2021