Clinical trial NCT03632876: Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD
Official title: Vitamin A in Sickle Cell Disease: Improving Sub-optimal Status With Supplementation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sickle Cell Anemia in Children
Vitamin A Deficiency in Children
Keywords: Retinol
Stable isotope dilution
DXA
retinyl palmitate
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Penn State University
name: Newcastle University
First posted: 2018-08-16
Enrollment: 42
Sex: ALL
Minimum age (years): 9
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Serum Vitamin A status
timeFrame: Change from baseline after supplementation for 8 weeks
Secondary outcomes:
measure: Vitamin A toxicity
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Height Z-score
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Weight Z-score
timeFrame: Change from baseline after supplementation for 8 weeks
measure: BMI Z-score
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Fat-free Mass
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Fat-free Mass
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Fat Mass
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Upper arm muscle area
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Upper arm fat area
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Muscle strength
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Jump strength
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Upper limb strength
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Muscle function
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Dietary Intake
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Coefficient of fat absorption
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Hemoglobin
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Hematocrit
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Fetal hemoglobin
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Mean corpuscular volume
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Mean corpuscular hemoglobin
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Mean corpuscular hemoglobin concentration
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Reticulocyte count
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Retinol binding protein, serum
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Retinol binding protein, urine
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Urine creatinine
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Serum creatinine
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Serum alanine aminotransferase
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Serum aspartate aminotransferase
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Serum gamma glutamyltransferase
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Serum alkaline phosphatase
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Serum bilirubin
timeFrame: Change from baseline after supplementation for 8 weeks
measure: High-sensitivity c-reactive protein
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Tumor necrosis factor alpha
timeFrame: Change from baseline after supplementation for 8 weeks
measure: White blood cell count
timeFrame: Change from baseline after supplementation for 8 weeks
measure: White blood cell differential
timeFrame: Change from baseline after supplementation for 8 weeks
measure: Lymphocyte subtypes
timeFrame: Change from baseline after supplementation for 8 weeks
Other outcomes:
measure: Total body vitamin A status via Stable Isotope Dilution
timeFrame: Change from baseline after supplementation for 8 weeks
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Virginia Stallings, MD
role: PRINCIPAL_INVESTIGATOR
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