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Sickle Cell Anemia in ChildrenNCT03632876

Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

A study testing retinyl palmitate in people with Sickle Cell Anemia in Children and Vitamin A Deficiency in Children, run by Children's Hospital of Philadelphia at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 9 years and olderHealthy volunteers can take part
What is being tested?
retinyl palmitate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
2 Oct 2015to 30 Sep 2016
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 9 years and older
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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)
Show all 10Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19146

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
retinyl palmitate
Keywords
Retinol, Stable isotope dilution, DXA, retinyl palmitate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • retinyl palmitateDietary supplement

    The intervention is a daily vitamin A supplement.

Study groups in NCT03632876
Study groupRoleWhat they receive
Lower Dose Vitamin AActive comparatorSubjects with SCD-SS in the lower dose Vitamin A arm receive 3000IU of retinyl palmitate daily for 8 weeks.
Receives: Dietary Supplement: retinyl palmitate
Higher Dose Vitamin AActive comparatorSubjects with SCD-SS in the higher dose Vitamin A arm receive 6000IU of retinyl palmitate daily for 8 weeks.
Receives: Dietary Supplement: retinyl palmitate
Healthy Comparison ArmNo interventionHealthy subjects receive no intervention and undergo comparisons to the two vitamin A supplementation arms at baseline.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serum Vitamin A status

    Serum vitamin A as measured by retinol

    Measured: Change from baseline after supplementation for 8 weeks

Secondary outcomes (36)
  1. Vitamin A toxicity

    Retinyl palmitate

    Measured: Change from baseline after supplementation for 8 weeks

  2. Height Z-score

    Measured on a stadiometer, compared to Center for Disease Control (CDC) reference standard to create a z-score

    Measured: Change from baseline after supplementation for 8 weeks

  3. Weight Z-score

    Measured on a standing scale, compared to CDC reference standard to create a z-score

    Measured: Change from baseline after supplementation for 8 weeks

  4. BMI Z-score

    Calculated using kg/m^2 and compared to CDC reference standards

    Measured: Change from baseline after supplementation for 8 weeks

  5. Fat-free Mass

    Calculated from dual-energy x-ray absorptiometry (DEXA) scan

    Measured: Change from baseline after supplementation for 8 weeks

  6. Fat-free Mass

    Calculated from DEXA scan

    Measured: Change from baseline after supplementation for 8 weeks

  7. Fat Mass

    Calculated from DEXA scan

    Measured: Change from baseline after supplementation for 8 weeks

  8. Upper arm muscle area

    Calculated from mid-upper arm circumference

    Measured: Change from baseline after supplementation for 8 weeks

  9. Upper arm fat area

    Calculated from mid-upper arm circumference and triceps skinfold thickness

    Measured: Change from baseline after supplementation for 8 weeks

  10. Muscle strength

    Directly measured with Biodex Multi-Joint System 3 Pro

    Measured: Change from baseline after supplementation for 8 weeks

  11. Jump strength

    Directly measured with Force Plate

    Measured: Change from baseline after supplementation for 8 weeks

  12. Upper limb strength

    Directly measured with hand-grip strength dynamometer

    Measured: Change from baseline after supplementation for 8 weeks

  13. Muscle function

    Directly measured with Bruininks-Oseretsky Test of Motor Proficiency

    Measured: Change from baseline after supplementation for 8 weeks

  14. Dietary Intake

    Analysis of a three-day food record

    Measured: Change from baseline after supplementation for 8 weeks

  15. Coefficient of fat absorption

    Calculated from 72-hour stool collection and dietary fat intake

    Measured: Change from baseline after supplementation for 8 weeks

  16. Hemoglobin

    Direct measurement through spectral absorption

    Measured: Change from baseline after supplementation for 8 weeks

  17. Hematocrit

    Direct measurement through spectral absorption

    Measured: Change from baseline after supplementation for 8 weeks

  18. Fetal hemoglobin

    Direct measurement through quantitative flow cytometry

    Measured: Change from baseline after supplementation for 8 weeks

  19. Mean corpuscular volume

    Direct measurement through quantitative flow cytometry

    Measured: Change from baseline after supplementation for 8 weeks

  20. Mean corpuscular hemoglobin

    Calculated from hemoglobin mass and erythrocyte count

    Measured: Change from baseline after supplementation for 8 weeks

  21. Mean corpuscular hemoglobin concentration

    Calculated from hemoglobin divided by hematocrit

    Measured: Change from baseline after supplementation for 8 weeks

  22. Reticulocyte count

    Direct measurement through quantitative flow cytometry

    Measured: Change from baseline after supplementation for 8 weeks

  23. Retinol binding protein, serum

    Direct measurement through quantitative nephelometry

    Measured: Change from baseline after supplementation for 8 weeks

  24. Retinol binding protein, urine

    Direct measurement through quantitative nephelometry

    Measured: Change from baseline after supplementation for 8 weeks

  25. Urine creatinine

    Direct measurement through quantitative spectrophotometry

    Measured: Change from baseline after supplementation for 8 weeks

  26. Serum creatinine

    Direct measurement through quantitative spectrophotometry

    Measured: Change from baseline after supplementation for 8 weeks

  27. Serum alanine aminotransferase

    Direct measurement through quantitative enzymatic assay

    Measured: Change from baseline after supplementation for 8 weeks

  28. Serum aspartate aminotransferase

    Direct measurement through quantitative enzymatic assay

    Measured: Change from baseline after supplementation for 8 weeks

  29. Serum gamma glutamyltransferase

    Direct measurement through quantitative enzymatic assay

    Measured: Change from baseline after supplementation for 8 weeks

  30. Serum alkaline phosphatase

    Direct measurement through quantitative enzymatic assay

    Measured: Change from baseline after supplementation for 8 weeks

  31. Serum bilirubin

    Direct measurement through quantitative quantitative spectrophotometry

    Measured: Change from baseline after supplementation for 8 weeks

  32. High-sensitivity c-reactive protein

    Direct measurement through quantitative quantitative immunoturbidimetry

    Measured: Change from baseline after supplementation for 8 weeks

  33. Tumor necrosis factor alpha

    Direct measurement through quantitative quantitative multiplex bead assay

    Measured: Change from baseline after supplementation for 8 weeks

  34. White blood cell count

    Direct measurement through automated cell count

    Measured: Change from baseline after supplementation for 8 weeks

  35. White blood cell differential

    Direct measurement through automated cell count

    Measured: Change from baseline after supplementation for 8 weeks

  36. Lymphocyte subtypes

    Direct measurement through quantitative flow cytometry

    Measured: Change from baseline after supplementation for 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2018
  2. Study start2 Oct 2015
  3. Primary completion30 Sep 2016
  4. Study completion30 Sep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03632876
Sponsor's protocol ID
13-010081
Status last verified
Aug 2018
First submitted
1 Aug 2018
Last updated
16 Aug 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported will be shared upon request, after deidentification.

Publications

  • 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.

    PubMed 17413103
  • 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

  • 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. doi: 10.1016/j.jpeds.2004.03.051.

    PubMed 15238915
  • 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.

    PubMed 11269606
  • 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.

    PubMed 22952182
  • 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.

    PubMed 9209171
  • 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.

    PubMed 10919941
  • Olson JA. Serum levels of vitamin A and carotenoids as reflectors of nutritional status. J Natl Cancer Inst. 1984 Dec;73(6):1439-44.

    PubMed 6439934
  • 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.

    PubMed 17467383
  • 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.

    PubMed 22369848
  • 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.

    PubMed 8120366
  • 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.

    PubMed 20181784
  • 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.

    PubMed 19814781
  • 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.

    PubMed 21228717

Questions about this trial

What is this clinical trial studying?

A study testing retinyl palmitate in people with Sickle Cell Anemia in Children and Vitamin A Deficiency in Children, run by Children's Hospital of Philadelphia at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serum Vitamin A status (time frame: Change from baseline after supplementation for 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03632876, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2018.

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