High Dose Vitamin D Supplementation in Children With Sickle Cell Disease

Safety and Efficacy of Monthly High-Dose Vitamin D3 Supplementation in Children and Adolescents With Sickle Cell Disease and Healthy Counter Parents

Suboptimal vitamin D status is well reported in sickle cell disease (SCD) patients and associated with a negative impact on health-related quality of life (HRQL). The investigators enrolled 42 SCD patients and 42 healthy controls, subjects within each group received monthly oral vitamin D3 dose according to the baseline status of vitamin D as follows: sufficient: 100,000 IU, insufficient: 150,000 IU, and deficient: 200,000 IU. The investigators assessed safety and efficacy on normalization of vitamin D level, bone mineral density (BMD), hand grip strength (HGS), and HRQL.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Sickle Cell Disease; Bone Mineral Density; Health Related Quality of Life; Hand Grip Strength
• Intervention / Treatment: Drug: Vitamin D3

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Sharkia
    • Zagazig, Sharkia, Egypt, 44519
      • Zagazig University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• children with SCD (HbSS, hemoglobin sickle beta zero (HbSβ0) thalassemia genotype), aged ≤ 18 years old, male or female study participants who were at a steady state (≥ one month from blood transfusion and ≥ 14 days from any acute sickle complication as hospitalization for Vaso occlusive crisis (VOC) or acute chest syndrome (ACS)), stable Hb level near their usual baseline and stable dose of Hydroxyurea (HÚ) mg/kg for at least 90 days prior to enrollment.
• A control group of 42 healthy age and sex-matching children

Exclusion Criteria:

• SCD patients who are on chronic blood transfusion therapy
• Comorbid chronic conditions
• Use of medications known to interfere with calcium or vitamin D absorption or metabolism
• Known hypercalcemia or vitamin D hypersensitivity
• Use of vitamin D therapy to treat vitamin D deficiency or rickets
• Urolithiasis, liver or renal impairment, and malabsorption disorders.
• Obese children with body mass index (BMI) > 85th percentile for age and sex

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral vitamin D3; Monthly oral vitamin D3 dose (100,000 IU,150,000 IU, and 200,000 IU)	Drug: Vitamin D3; Subjects within SCD as well as healthy controls, received monthly oral vitamin D3 dose, for 6 months, according to the baseline status of vitamin D as follows: sufficient (>30 ng/mL): 100,000 IU, insufficient (20-29.9 ng/mL): 150,000 IU, and deficient (<20 ng/mL): 200,000 IU.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum 25(OH)D level	Serum 25(OH)D level change from baseline at 6 months	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density (BMD)	BMD was evaluated at the posterior-anterior spine, Z-scores were used to interpret the results, with Z-scores less than -2 standard deviation (SD) being regarded as abnormal	up to 6 months
Maximum handgrip strength (HGS)	Hand grip power using a handheld dynamometer.	up to 6 months
Health related quality of life (HRQL)	Health related quality of life (HRQL) assessed by HRQL questionnaires, The questionnaire was divided into eight subscales: physical function, role limitations resulting from physical health, bodily pain, general health perception, vitality, social function, role limitations resulting from emotional problems, and mental health. For each subscale: higher score indicated good health and ranged from 0 to 100.	up to 6 months
Serum concentrations of C reactive protein (CRP)	Serum concentrations of inflammatory marker (CRP) level change from baseline	up to 6 months
Serum concentrations of Erythrocyte sedimentation rate (ESR)	Serum concentrations of inflammatory marker (ESR) level change from baseline	up to 6 months
Safety reporting of any adverse events	e.g. nausea, drowsiness, vomiting, loss of appetite, constipation, confusion, cardiac arrhythmias, renal failure, coma	up to 6 months
Safety measurements of serum Ca	serum Ca levels	at 3 and 6 months
childhood health assessment	Assessed by childhood health assessment questionnaire (CHAQ), There are four potential responses to each question: "without any difficulty" (score 0); "with some difficulty" (score 1); "with much difficulty" (score 2); and "unable to do" (score 3). A summary score known as CHAQ-DI/, which varies from 0 to 3, is calculated by averaging the highest score in each domain. For a CHAQ-DI score to be considered minimally clinically significant, it must be ≥ 0.75.	up to 6 months
Safety measurements of serum 25(OH)D levels	serum 25(OH)D levels	at 3 and 6 months

Collaborators and Investigators

• Sponsor: Zagazig University

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Actual): January 30, 2024
• Study Completion (Actual): February 10, 2024

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Anemia; Avitaminosis; Deficiency Diseases; Malnutrition; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Vitamin D Deficiency; 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: 10584-2/5-2023

Drug and device information, study documents

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