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| Name | Class |
|---|---|
| Penn State University | OTHER |
| Newcastle University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lower Dose Vitamin A | Active Comparator | Subjects with SCD-SS in the lower dose Vitamin A arm receive 3000IU of retinyl palmitate daily for 8 weeks. |
|
| Higher Dose Vitamin A | Active Comparator | Subjects with SCD-SS in the higher dose Vitamin A arm receive 6000IU of retinyl palmitate daily for 8 weeks. |
|
| Healthy Comparison Arm | No Intervention | Healthy subjects receive no intervention and undergo comparisons to the two vitamin A supplementation arms at baseline. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| retinyl palmitate | Dietary Supplement | The intervention is a daily vitamin A supplement. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Serum Vitamin A status | Serum vitamin A as measured by retinol | Change from baseline after supplementation for 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Vitamin A toxicity | Retinyl palmitate | Change from baseline after supplementation for 8 weeks |
| Height Z-score | Measured on a stadiometer, compared to Center for Disease Control (CDC) reference standard to create a z-score |
| Measure | Description | Time Frame |
|---|---|---|
| Total body vitamin A status via Stable Isotope Dilution | compartmental modeling of [13C10]-retinyl acetate, measured by high performance liquid chromatography/mass spectroscopy | Change from baseline after supplementation for 8 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Virginia Stallings, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19146 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17413103 | Background | Ribaya-Mercado JD, Maramag CC, Tengco LW, Dolnikowski GG, Blumberg JB, Solon FS. Carotene-rich plant foods ingested with minimal dietary fat enhance the total-body vitamin A pool size in Filipino schoolchildren as assessed by stable-isotope-dilution methodology. Am J Clin Nutr. 2007 Apr;85(4):1041-9. doi: 10.1093/ajcn/85.4.1041. | |
| Background | Solomons NW. Vitamin A. In: B.Bowman, R.Russell, editors. Present Knowledge in Nutrition, Volume I. 9 ed. Washington DC: International Life Science Institute Press; 2006:157-183 | ||
| Background | Ross CA. Vitamin A and carotenoids. In: M.E.Shils, M.Shike, C.A.Ross, B.Caballero, R.J.Cousins, editors. Modern Nutrition in Health and Disease. 10 ed. Philadelphia: Lippincott, Williams and Wilkins; 2006:351-375 | ||
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Individual participant data that underlie the results reported will be shared upon request, after deidentification.
The data will be available immediately upon publication.
Contact brownellj@email.chop.edu. Requestors will need to sign a data access agreement.
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| ID | Term |
|---|---|
| C014794 | retinol palmitate |
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Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.
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| Change from baseline after supplementation for 8 weeks |
| Weight Z-score | Measured on a standing scale, compared to CDC reference standard to create a z-score | Change from baseline after supplementation for 8 weeks |
| BMI Z-score | Calculated using kg/m^2 and compared to CDC reference standards | Change from baseline after supplementation for 8 weeks |
| Fat-free Mass | Calculated from dual-energy x-ray absorptiometry (DEXA) scan | Change from baseline after supplementation for 8 weeks |
| Fat-free Mass | Calculated from DEXA scan | Change from baseline after supplementation for 8 weeks |
| Fat Mass | Calculated from DEXA scan | Change from baseline after supplementation for 8 weeks |
| Upper arm muscle area | Calculated from mid-upper arm circumference | Change from baseline after supplementation for 8 weeks |
| Upper arm fat area | Calculated from mid-upper arm circumference and triceps skinfold thickness | Change from baseline after supplementation for 8 weeks |
| Muscle strength | Directly measured with Biodex Multi-Joint System 3 Pro | Change from baseline after supplementation for 8 weeks |
| Jump strength | Directly measured with Force Plate | Change from baseline after supplementation for 8 weeks |
| Upper limb strength | Directly measured with hand-grip strength dynamometer | Change from baseline after supplementation for 8 weeks |
| Muscle function | Directly measured with Bruininks-Oseretsky Test of Motor Proficiency | Change from baseline after supplementation for 8 weeks |
| Dietary Intake | Analysis of a three-day food record | Change from baseline after supplementation for 8 weeks |
| Coefficient of fat absorption | Calculated from 72-hour stool collection and dietary fat intake | Change from baseline after supplementation for 8 weeks |
| Hemoglobin | Direct measurement through spectral absorption | Change from baseline after supplementation for 8 weeks |
| Hematocrit | Direct measurement through spectral absorption | Change from baseline after supplementation for 8 weeks |
| Fetal hemoglobin | Direct measurement through quantitative flow cytometry | Change from baseline after supplementation for 8 weeks |
| Mean corpuscular volume | Direct measurement through quantitative flow cytometry | Change from baseline after supplementation for 8 weeks |
| Mean corpuscular hemoglobin | Calculated from hemoglobin mass and erythrocyte count | Change from baseline after supplementation for 8 weeks |
| Mean corpuscular hemoglobin concentration | Calculated from hemoglobin divided by hematocrit | Change from baseline after supplementation for 8 weeks |
| Reticulocyte count | Direct measurement through quantitative flow cytometry | Change from baseline after supplementation for 8 weeks |
| Retinol binding protein, serum | Direct measurement through quantitative nephelometry | Change from baseline after supplementation for 8 weeks |
| Retinol binding protein, urine | Direct measurement through quantitative nephelometry | Change from baseline after supplementation for 8 weeks |
| Urine creatinine | Direct measurement through quantitative spectrophotometry | Change from baseline after supplementation for 8 weeks |
| Serum creatinine | Direct measurement through quantitative spectrophotometry | Change from baseline after supplementation for 8 weeks |
| Serum alanine aminotransferase | Direct measurement through quantitative enzymatic assay | Change from baseline after supplementation for 8 weeks |
| Serum aspartate aminotransferase | Direct measurement through quantitative enzymatic assay | Change from baseline after supplementation for 8 weeks |
| Serum gamma glutamyltransferase | Direct measurement through quantitative enzymatic assay | Change from baseline after supplementation for 8 weeks |
| Serum alkaline phosphatase | Direct measurement through quantitative enzymatic assay | Change from baseline after supplementation for 8 weeks |
| Serum bilirubin | Direct measurement through quantitative quantitative spectrophotometry | Change from baseline after supplementation for 8 weeks |
| High-sensitivity c-reactive protein | Direct measurement through quantitative quantitative immunoturbidimetry | Change from baseline after supplementation for 8 weeks |
| Tumor necrosis factor alpha | Direct measurement through quantitative quantitative multiplex bead assay | Change from baseline after supplementation for 8 weeks |
| White blood cell count | Direct measurement through automated cell count | Change from baseline after supplementation for 8 weeks |
| White blood cell differential | Direct measurement through automated cell count | Change from baseline after supplementation for 8 weeks |
| Lymphocyte subtypes | Direct measurement through quantitative flow cytometry | Change from baseline after supplementation for 8 weeks |
| Background |
| Schall JI, Zemel BS, Kawchak DA, Ohene-Frempong K, Stallings VA. Vitamin A status, hospitalizations, and other outcomes in young children with sickle cell disease. J Pediatr. 2004 Jul;145(1):99-106. doi: 10.1016/j.jpeds.2004.03.051. |
| 11269606 | Background | Trumbo P, Yates AA, Schlicker S, Poos M. Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. J Am Diet Assoc. 2001 Mar;101(3):294-301. doi: 10.1016/S0002-8223(01)00078-5. No abstract available. |
| 22952182 | Background | Dougherty KA, Schall JI, Kawchak DA, Green MH, Ohene-Frempong K, Zemel BS, Stallings VA. No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease. Am J Clin Nutr. 2012 Oct;96(4):932-40. doi: 10.3945/ajcn.112.035725. Epub 2012 Sep 5. |
| 9209171 | Background | Haskell MJ, Handelman GJ, Peerson JM, Jones AD, Rabbi MA, Awal MA, Wahed MA, Mahalanabis D, Brown KH. Assessment of vitamin A status by the deuterated-retinol-dilution technique and comparison with hepatic vitamin A concentration in Bangladeshi surgical patients. Am J Clin Nutr. 1997 Jul;66(1):67-74. doi: 10.1093/ajcn/66.1.67. |
| 10919941 | Background | Ribaya-Mercado JD, Solon FS, Solon MA, Cabal-Barza MA, Perfecto CS, Tang G, Solon JA, Fjeld CR, Russell RM. Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children varies inversely with vitamin A status. Am J Clin Nutr. 2000 Aug;72(2):455-65. doi: 10.1093/ajcn/72.2.455. |
| 6439934 | Background | Olson JA. Serum levels of vitamin A and carotenoids as reflectors of nutritional status. J Natl Cancer Inst. 1984 Dec;73(6):1439-44. |
| 17467383 | Background | Kawchak DA, Schall JI, Zemel BS, Ohene-Frempong K, Stallings VA. Adequacy of dietary intake declines with age in children with sickle cell disease. J Am Diet Assoc. 2007 May;107(5):843-8. doi: 10.1016/j.jada.2007.02.015. |
| 22369848 | Background | Garcia OP. Effect of vitamin A deficiency on the immune response in obesity. Proc Nutr Soc. 2012 May;71(2):290-7. doi: 10.1017/S0029665112000079. Epub 2012 Feb 28. |
| 8120366 | Background | Cantorna MT, Nashold FE, Hayes CE. In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function. J Immunol. 1994 Feb 15;152(4):1515-22. |
| 20181784 | Background | Esteban-Pretel G, Marin MP, Cabezuelo F, Moreno V, Renau-Piqueras J, Timoneda J, Barber T. Vitamin A deficiency increases protein catabolism and induces urea cycle enzymes in rats. J Nutr. 2010 Apr;140(4):792-8. doi: 10.3945/jn.109.119388. Epub 2010 Feb 24. |
| 19814781 | Background | Kennedy KA, Porter T, Mehta V, Ryan SD, Price F, Peshdary V, Karamboulas C, Savage J, Drysdale TA, Li SC, Bennett SA, Skerjanc IS. Retinoic acid enhances skeletal muscle progenitor formation and bypasses inhibition by bone morphogenetic protein 4 but not dominant negative beta-catenin. BMC Biol. 2009 Oct 8;7:67. doi: 10.1186/1741-7007-7-67. |
| 21228717 | Background | Dougherty KA, Schall JI, Rovner AJ, Stallings VA, Zemel BS. Attenuated maximal muscle strength and peak power in children with sickle cell disease. J Pediatr Hematol Oncol. 2011 Mar;33(2):93-7. doi: 10.1097/MPH.0b013e318200ef49. |
| 17413865 | Background | Zemel BS, Kawchak DA, Ohene-Frempong K, Schall JI, Stallings VA. Effects of delayed pubertal development, nutritional status, and disease severity on longitudinal patterns of growth failure in children with sickle cell disease. Pediatr Res. 2007 May;61(5 Pt 1):607-13. doi: 10.1203/pdr.0b013e318045bdca. |
| 12221269 | Background | Allen LH, Haskell M. Estimating the potential for vitamin A toxicity in women and young children. J Nutr. 2002 Sep;132(9 Suppl):2907S-2919S. doi: 10.1093/jn/132.9.2907S. |
| 37468045 | Derived | Ford JL, Green MH, Brownell JN, Green JB, Oxley A, Lietz G, Schall JI, Stallings VA. Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation. J Nutr. 2023 Sep;153(9):2762-2771. doi: 10.1016/j.tjnut.2023.07.004. Epub 2023 Jul 17. |