Sickle Cell Anemia in Children, Vitamin A Deficiency in Children
Conditions
Keywords
Retinol, Stable isotope dilution, DXA, retinyl palmitate
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.
Interventions
DIETARY_SUPPLEMENTretinyl palmitate
The intervention is a daily vitamin A supplement.
Sponsors
Penn State University
Newcastle University
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.
Eligibility
Sex/Gender
ALL
Age
9 Years to No maximum
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Vitamin A status | Change from baseline after supplementation for 8 weeks | Serum vitamin A as measured by retinol |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vitamin A toxicity | Change from baseline after supplementation for 8 weeks | Retinyl palmitate |
| 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 |
| 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 dual-energy x-ray absorptiometry (DEXA) scan |
| Fat Mass | Change from baseline after supplementation for 8 weeks | Calculated from DEXA scan |
| 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 |
| Muscle strength | Change from baseline after supplementation for 8 weeks | Directly measured with Biodex Multi-Joint System 3 Pro |
| Jump strength | Change from baseline after supplementation for 8 weeks | Directly measured with Force Plate |
| Upper limb strength | Change from baseline after supplementation for 8 weeks | Directly measured with hand-grip strength dynamometer |
| Muscle function | Change from baseline after supplementation for 8 weeks | Directly measured with Bruininks-Oseretsky Test of Motor Proficiency |
| Dietary Intake | Change from baseline after supplementation for 8 weeks | Analysis of a three-day food record |
| 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 |
| 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 |
| Mean corpuscular hemoglobin concentration | Change from baseline after supplementation for 8 weeks | Calculated from hemoglobin divided by hematocrit |
| 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 |
| Retinol binding protein, urine | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative nephelometry |
| Urine creatinine | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative spectrophotometry |
| Serum creatinine | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative spectrophotometry |
| 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 gamma glutamyltransferase | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative enzymatic assay |
| Serum alkaline phosphatase | 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 |
| High-sensitivity c-reactive protein | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative quantitative immunoturbidimetry |
| Tumor necrosis factor alpha | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative quantitative multiplex bead assay |
| White blood cell count | Change from baseline after supplementation for 8 weeks | Direct measurement through automated cell count |
| White blood cell differential | Change from baseline after supplementation for 8 weeks | Direct measurement through automated cell count |
| Lymphocyte subtypes | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative flow cytometry |
| Mean corpuscular volume | Change from baseline after supplementation for 8 weeks | Direct measurement through quantitative flow cytometry |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total body vitamin A status via Stable Isotope Dilution | Change from baseline after supplementation for 8 weeks | compartmental modeling of \[13C10\]-retinyl acetate, measured by high performance liquid chromatography/mass spectroscopy |
Countries
United States
Outcome results
None listed