Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

Sickle Cell Anemia in Children Clinical Trial

Official title:

Vitamin A in Sickle Cell Disease: Improving Sub-optimal Status With Supplementation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03632876
• Other study ID #: 13-010081
• Status: Completed
• Phase: N/A
• Start date: October 2, 2015
• Est. completion date: September 30, 2016

Study information

• Verified date: August 2018
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 30, 2016
• Est. primary completion date: September 30, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Night Blindness
• Sickle Cell Anemia in Children
• Vitamin A Deficiency
• Vitamin A Deficiency in Children

Intervention

Dietary Supplement:
• retinyl palmitate
The intervention is a daily vitamin A supplement.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Newcastle University, Penn State University

Country where clinical trial is conducted

United States, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. Epub 2012 Sep 5. — View Citation

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. — View Citation

Esteban-Pretel G, Marín 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. — View Citation

García 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. Review. — View Citation

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. Erratum in: Am J Clin Nutr 1999 Mar;69(3):576. — View Citation

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. — View Citation

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. — View Citation

Olson JA. Serum levels of vitamin A and carotenoids as reflectors of nutritional status. J Natl Cancer Inst. 1984 Dec;73(6):1439-44. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

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