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Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

Primary Purpose

Sickle Cell Anemia in Children, Vitamin A Deficiency in Children

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
retinyl palmitate
Sponsored by
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Anemia in Children focused on measuring Retinol, Stable isotope dilution, DXA, retinyl palmitate

Eligibility Criteria

9 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

No Intervention

Arm Label

Lower Dose Vitamin A

Higher Dose Vitamin A

Healthy Comparison Arm

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Serum Vitamin A status
Serum vitamin A as measured by retinol

Secondary Outcome Measures

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

Full Information

First Posted
August 1, 2018
Last Updated
August 13, 2018
Sponsor
Children's Hospital of Philadelphia
Collaborators
Penn State University, Newcastle University
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1. Study Identification

Unique Protocol Identification Number
NCT03632876
Brief Title
Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD
Official Title
Vitamin A in Sickle Cell Disease: Improving Sub-optimal Status With Supplementation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2, 2015 (Actual)
Primary Completion Date
September 30, 2016 (Actual)
Study Completion Date
September 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
Penn State University, Newcastle University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Anemia in Children, Vitamin A Deficiency in Children
Keywords
Retinol, Stable isotope dilution, DXA, retinyl palmitate

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Subjects in parallel groups will be randomized to one of two doses of vitamin A supplementation.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lower Dose Vitamin A
Arm Type
Active Comparator
Arm Description
Subjects with SCD-SS in the lower dose Vitamin A arm receive 3000IU of retinyl palmitate daily for 8 weeks.
Arm Title
Higher Dose Vitamin A
Arm Type
Active Comparator
Arm Description
Subjects with SCD-SS in the higher dose Vitamin A arm receive 6000IU of retinyl palmitate daily for 8 weeks.
Arm Title
Healthy Comparison Arm
Arm Type
No Intervention
Arm Description
Healthy subjects receive no intervention and undergo comparisons to the two vitamin A supplementation arms at baseline.
Intervention Type
Dietary Supplement
Intervention Name(s)
retinyl palmitate
Intervention Description
The intervention is a daily vitamin A supplement.
Primary Outcome Measure Information:
Title
Serum Vitamin A status
Description
Serum vitamin A as measured by retinol
Time Frame
Change from baseline after supplementation for 8 weeks
Secondary Outcome Measure Information:
Title
Vitamin A toxicity
Description
Retinyl palmitate
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Height Z-score
Description
Measured on a stadiometer, compared to Center for Disease Control (CDC) reference standard to create a z-score
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Weight Z-score
Description
Measured on a standing scale, compared to CDC reference standard to create a z-score
Time Frame
Change from baseline after supplementation for 8 weeks
Title
BMI Z-score
Description
Calculated using kg/m^2 and compared to CDC reference standards
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Fat-free Mass
Description
Calculated from dual-energy x-ray absorptiometry (DEXA) scan
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Fat-free Mass
Description
Calculated from DEXA scan
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Fat Mass
Description
Calculated from DEXA scan
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Upper arm muscle area
Description
Calculated from mid-upper arm circumference
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Upper arm fat area
Description
Calculated from mid-upper arm circumference and triceps skinfold thickness
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Muscle strength
Description
Directly measured with Biodex Multi-Joint System 3 Pro
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Jump strength
Description
Directly measured with Force Plate
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Upper limb strength
Description
Directly measured with hand-grip strength dynamometer
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Muscle function
Description
Directly measured with Bruininks-Oseretsky Test of Motor Proficiency
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Dietary Intake
Description
Analysis of a three-day food record
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Coefficient of fat absorption
Description
Calculated from 72-hour stool collection and dietary fat intake
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Hemoglobin
Description
Direct measurement through spectral absorption
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Hematocrit
Description
Direct measurement through spectral absorption
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Fetal hemoglobin
Description
Direct measurement through quantitative flow cytometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Mean corpuscular volume
Description
Direct measurement through quantitative flow cytometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Mean corpuscular hemoglobin
Description
Calculated from hemoglobin mass and erythrocyte count
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Mean corpuscular hemoglobin concentration
Description
Calculated from hemoglobin divided by hematocrit
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Reticulocyte count
Description
Direct measurement through quantitative flow cytometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Retinol binding protein, serum
Description
Direct measurement through quantitative nephelometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Retinol binding protein, urine
Description
Direct measurement through quantitative nephelometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Urine creatinine
Description
Direct measurement through quantitative spectrophotometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Serum creatinine
Description
Direct measurement through quantitative spectrophotometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Serum alanine aminotransferase
Description
Direct measurement through quantitative enzymatic assay
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Serum aspartate aminotransferase
Description
Direct measurement through quantitative enzymatic assay
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Serum gamma glutamyltransferase
Description
Direct measurement through quantitative enzymatic assay
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Serum alkaline phosphatase
Description
Direct measurement through quantitative enzymatic assay
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Serum bilirubin
Description
Direct measurement through quantitative quantitative spectrophotometry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
High-sensitivity c-reactive protein
Description
Direct measurement through quantitative quantitative immunoturbidimetry
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Tumor necrosis factor alpha
Description
Direct measurement through quantitative quantitative multiplex bead assay
Time Frame
Change from baseline after supplementation for 8 weeks
Title
White blood cell count
Description
Direct measurement through automated cell count
Time Frame
Change from baseline after supplementation for 8 weeks
Title
White blood cell differential
Description
Direct measurement through automated cell count
Time Frame
Change from baseline after supplementation for 8 weeks
Title
Lymphocyte subtypes
Description
Direct measurement through quantitative flow cytometry
Time Frame
Change from baseline after supplementation for 8 weeks
Other Pre-specified Outcome Measures:
Title
Total body vitamin A status via Stable Isotope Dilution
Description
compartmental modeling of [13C10]-retinyl acetate, measured by high performance liquid chromatography/mass spectroscopy
Time Frame
Change from baseline after supplementation for 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Virginia Stallings, MD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19146
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported will be shared upon request, after deidentification.
IPD Sharing Time Frame
The data will be available immediately upon publication.
IPD Sharing Access Criteria
Contact brownellj@email.chop.edu. Requestors will need to sign a data access agreement.
Citations:
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17413103
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Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

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