Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

NCT ID: NCT03632876

Last Updated: 2018-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-02

Study Completion Date

2016-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sickle Cell Anemia in Children Vitamin A Deficiency in Children

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Lower Dose Vitamin A

Subjects with SCD-SS in the lower dose Vitamin A arm receive 3000IU of retinyl palmitate daily for 8 weeks.

Group Type ACTIVE_COMPARATOR

retinyl palmitate

Intervention Type DIETARY_SUPPLEMENT

The intervention is a daily vitamin A supplement.

Higher Dose Vitamin A

Subjects with SCD-SS in the higher dose Vitamin A arm receive 6000IU of retinyl palmitate daily for 8 weeks.

Group Type ACTIVE_COMPARATOR

retinyl palmitate

Intervention Type DIETARY_SUPPLEMENT

The intervention is a daily vitamin A supplement.

Healthy Comparison Arm

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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retinyl palmitate

The intervention is a daily vitamin A supplement.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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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)
Minimum Eligible Age

9 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Penn State University

OTHER

Sponsor Role collaborator

Newcastle University

OTHER

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Virginia Stallings, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17413103 (View on PubMed)

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

Reference Type 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

Reference Type 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.

Reference Type BACKGROUND
PMID: 15238915 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11269606 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22952182 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9209171 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10919941 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 6439934 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17467383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22369848 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8120366 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20181784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19814781 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21228717 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17413865 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12221269 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37468045 (View on PubMed)

Other Identifiers

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13-010081

Identifier Type: -

Identifier Source: org_study_id

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