Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

Not Applicable

Completed

• Conditions: Vitamin A Deficiency in Children; Sickle Cell Anemia in Children

• Registration Number: NCT03632876
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

This study establishes the safety and efficacy of vit A supplementation doses (3000 and 6000 IU/d) over 8 weeks in children with SCD-SS, ages 9 and older and test the impact of vit A supplementation on key functional and clinical outcomes. Additionally, vitamin A status is assessed in healthy children ages 9 and older to compare to subjects with SCD-SS.

Detailed Description

Suboptimal vitamin A (vit A) status is prevalent in children with type SS sickle cell disease (SCD-SS) and associated with hospitalizations and poor growth and hematological status. Preliminary data in children with SCD-SS show that vit A supplementation at the dose recommended for healthy children failed to improve vit A status, resulting in no change in hospitalizations, growth or dark adaptation. This indicates an increased vit A requirement most likely due to chronic inflammation, low vit A intake and possible stool or urine loss. The dose of vit A needed to optimize vit A status in subjects with SCD-SS is unknown.

Study Timeline

• Study Start: 2015-10-02
• Primary Completion: 2016-09-30
• Study Completion: 2016-09-30
• Status Verified: 2018-08
• Study First Submitted: 2018-08-01
• Study First Submitted QC: 2018-08-13
• Last Update Submitted: 2018-08-13
• Study First Posted: 2018-08-16
• Last Update Posted: 2018-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• Sickle cell disease, SS genotype (subjects with sickle cell disease only)
• Usual state of good health (no hospitalizations, emergency room visits, or unscheduled acute illness clinic visits for two weeks prior to screening)
• Commitment to a 119-day study (subjects with sickle cell disease only), or a 4-day study (healthy volunteers only)

Exclusion Criteria

• Hydroxyurea initiated within the previous 6 weeks (subjects with sickle cell disease only)
• History of stroke (subjects with sickle cell disease only)
• Other chronic conditions that may affect growth, dietary intake or nutritional status
• Retinoic acid (topical or oral), weight loss medication and/or lipid lowering medications
• Subjects with a BMI greater than 98th percentile for age and sex
• Pregnant or lactating females (subjects who become pregnant during the course of the study will not continue participation)
• Liver function tests >4 x upper limit of reference range
• Participation in another study with impact on vitamin A status (subjects with sickle cell disease only)
• Use of multi-vitamin or commercial nutritional supplements containing vitamin A (those who are willing to discontinue these supplements, with the approval of the medical care team, will be eligible for the study after a 1 month washout period. Subjects taking nutritional products without vitamin A will be eligible)
• Inability to swallow pills (subjects with sickle cell disease only)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Serum Vitamin A status	Change from baseline after supplementation for 8 weeks	Serum vitamin A as measured by retinol

Secondary Outcome Measures

Name	Time	Method
Coefficient of fat absorption	Change from baseline after supplementation for 8 weeks	Calculated from 72-hour stool collection and dietary fat intake
Hemoglobin	Change from baseline after supplementation for 8 weeks	Direct measurement through spectral absorption
Height Z-score	Change from baseline after supplementation for 8 weeks	Measured on a stadiometer, compared to Center for Disease Control (CDC) reference standard to create a z-score
Weight Z-score	Change from baseline after supplementation for 8 weeks	Measured on a standing scale, compared to CDC reference standard to create a z-score
Muscle strength	Change from baseline after supplementation for 8 weeks	Directly measured with Biodex Multi-Joint System 3 Pro
White blood cell count	Change from baseline after supplementation for 8 weeks	Direct measurement through automated cell count
Upper limb strength	Change from baseline after supplementation for 8 weeks	Directly measured with hand-grip strength dynamometer
Reticulocyte count	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative flow cytometry
Retinol binding protein, serum	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative nephelometry
White blood cell differential	Change from baseline after supplementation for 8 weeks	Direct measurement through automated cell count
Vitamin A toxicity	Change from baseline after supplementation for 8 weeks	Retinyl palmitate
Upper arm muscle area	Change from baseline after supplementation for 8 weeks	Calculated from mid-upper arm circumference
Upper arm fat area	Change from baseline after supplementation for 8 weeks	Calculated from mid-upper arm circumference and triceps skinfold thickness
Jump strength	Change from baseline after supplementation for 8 weeks	Directly measured with Force Plate
Retinol binding protein, urine	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative nephelometry
Dietary Intake	Change from baseline after supplementation for 8 weeks	Analysis of a three-day food record
Hematocrit	Change from baseline after supplementation for 8 weeks	Direct measurement through spectral absorption
Fetal hemoglobin	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative flow cytometry
Mean corpuscular hemoglobin	Change from baseline after supplementation for 8 weeks	Calculated from hemoglobin mass and erythrocyte count
BMI Z-score	Change from baseline after supplementation for 8 weeks	Calculated using kg/m\^2 and compared to CDC reference standards
Fat-free Mass	Change from baseline after supplementation for 8 weeks	Calculated from DEXA scan
Fat Mass	Change from baseline after supplementation for 8 weeks	Calculated from DEXA scan
Muscle function	Change from baseline after supplementation for 8 weeks	Directly measured with Bruininks-Oseretsky Test of Motor Proficiency
Mean corpuscular volume	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative flow cytometry
Serum alanine aminotransferase	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative enzymatic assay
Serum aspartate aminotransferase	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative enzymatic assay
Serum bilirubin	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative quantitative spectrophotometry
Tumor necrosis factor alpha	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative quantitative multiplex bead assay
Mean corpuscular hemoglobin concentration	Change from baseline after supplementation for 8 weeks	Calculated from hemoglobin divided by hematocrit
Urine creatinine	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative spectrophotometry
Serum alkaline phosphatase	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative enzymatic assay
High-sensitivity c-reactive protein	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative quantitative immunoturbidimetry
Serum creatinine	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative spectrophotometry
Serum gamma glutamyltransferase	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative enzymatic assay
Lymphocyte subtypes	Change from baseline after supplementation for 8 weeks	Direct measurement through quantitative flow cytometry

Trial Locations

Locations (1)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States