Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

NCT03632876 | Completed

• 1 other identifier: 13-010081
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Anemia in Children; Vitamin A Deficiency in Children

Keywords

Retinol; Stable isotope dilution; DXA; retinyl palmitate

Outcome Measures

Primary Outcomes (1)

• Serum Vitamin A status

  Serum vitamin A as measured by retinol

  Change from baseline after supplementation for 8 weeks

Secondary Outcomes (36)

• Vitamin A toxicity

  Change from baseline after supplementation for 8 weeks

• Height Z-score

  Change from baseline after supplementation for 8 weeks

• Weight Z-score

  Change from baseline after supplementation for 8 weeks

• BMI Z-score

  Change from baseline after supplementation for 8 weeks

• Fat-free Mass

  Change from baseline after supplementation for 8 weeks

Other Outcomes (1)

• Total body vitamin A status via Stable Isotope Dilution

  Change from baseline after supplementation for 8 weeks

Study Arms (3)

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.

Dietary Supplement: retinyl palmitate

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.

Dietary Supplement: retinyl palmitate

Healthy Comparison Arm

NO INTERVENTION

Healthy subjects receive no intervention and undergo comparisons to the two vitamin A supplementation arms at baseline.

Interventions

retinyl palmitate DIETARY_SUPPLEMENT

The intervention is a daily vitamin A supplement.

Higher Dose Vitamin A; Lower Dose Vitamin A

Eligibility Criteria

• Age: 9 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Penn State University: collaborator
• Newcastle University: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19146, United States

Location

Related Publications (18)

• 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.

  PMID: 17413103 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

  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.

  PMID: 15238915 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.

  PMID: 11269606 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.

  PMID: 22952182 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.

  PMID: 9209171 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.

  PMID: 10919941 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.

  PMID: 6439934 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.

  PMID: 17467383 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.

  PMID: 22369848 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.

  PMID: 8120366 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.

  PMID: 20181784 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.

  PMID: 19814781 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.

  PMID: 21228717 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.

  PMID: 17413865 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.

  PMID: 12221269 BACKGROUND

• 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.

  PMID: 37468045 DERIVED

MeSH Terms

Interventions

retinol palmitate

Study Officials

• Virginia Stallings, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 16, 2018
• Study Start: October 2, 2015
• Primary Completion: September 30, 2016
• Study Completion: September 30, 2016
• Last Updated: August 16, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The data will be available immediately upon publication.
• Access Criteria: Contact brownellj@email.chop.edu. Requestors will need to sign a data access agreement.

Locations

US (1)