Nutritional Outcomes After Vitamin A Supplementation in Subjects With SCD

August 13, 2018 updated by: Children's Hospital of Philadelphia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19146
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

9 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Lower Dose Vitamin A
Subjects with SCD-SS in the lower dose Vitamin A arm receive 3000IU of retinyl palmitate daily for 8 weeks.
Dietary supplement: retinyl palmitate
The intervention is a daily vitamin A supplement.
ACTIVE_COMPARATOR: Higher Dose Vitamin A
Subjects with SCD-SS in the higher dose Vitamin A arm receive 6000IU of retinyl palmitate daily for 8 weeks.
Dietary supplement: retinyl palmitate
The intervention is a daily vitamin A supplement.
NO_INTERVENTION: Healthy Comparison Arm
Healthy subjects receive no intervention and undergo comparisons to the two vitamin A supplementation arms at baseline.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Serum Vitamin A status
Time Frame: Change from baseline after supplementation for 8 weeks
Serum vitamin A as measured by retinol
Change from baseline after supplementation for 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Vitamin A toxicity
Time Frame: Change from baseline after supplementation for 8 weeks
Retinyl palmitate
Change from baseline after supplementation for 8 weeks
Height Z-score
Time Frame: Change from baseline after supplementation for 8 weeks
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
Weight Z-score
Time Frame: Change from baseline after supplementation for 8 weeks
Measured on a standing scale, compared to CDC reference standard to create a z-score
Change from baseline after supplementation for 8 weeks
BMI Z-score
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated using kg/m^2 and compared to CDC reference standards
Change from baseline after supplementation for 8 weeks
Fat-free Mass
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from dual-energy x-ray absorptiometry (DEXA) scan
Change from baseline after supplementation for 8 weeks
Fat-free Mass
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from DEXA scan
Change from baseline after supplementation for 8 weeks
Fat Mass
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from DEXA scan
Change from baseline after supplementation for 8 weeks
Upper arm muscle area
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from mid-upper arm circumference
Change from baseline after supplementation for 8 weeks
Upper arm fat area
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from mid-upper arm circumference and triceps skinfold thickness
Change from baseline after supplementation for 8 weeks
Muscle strength
Time Frame: Change from baseline after supplementation for 8 weeks
Directly measured with Biodex Multi-Joint System 3 Pro
Change from baseline after supplementation for 8 weeks
Jump strength
Time Frame: Change from baseline after supplementation for 8 weeks
Directly measured with Force Plate
Change from baseline after supplementation for 8 weeks
Upper limb strength
Time Frame: Change from baseline after supplementation for 8 weeks
Directly measured with hand-grip strength dynamometer
Change from baseline after supplementation for 8 weeks
Muscle function
Time Frame: Change from baseline after supplementation for 8 weeks
Directly measured with Bruininks-Oseretsky Test of Motor Proficiency
Change from baseline after supplementation for 8 weeks
Dietary Intake
Time Frame: Change from baseline after supplementation for 8 weeks
Analysis of a three-day food record
Change from baseline after supplementation for 8 weeks
Coefficient of fat absorption
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from 72-hour stool collection and dietary fat intake
Change from baseline after supplementation for 8 weeks
Hemoglobin
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through spectral absorption
Change from baseline after supplementation for 8 weeks
Hematocrit
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through spectral absorption
Change from baseline after supplementation for 8 weeks
Fetal hemoglobin
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative flow cytometry
Change from baseline after supplementation for 8 weeks
Mean corpuscular volume
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative flow cytometry
Change from baseline after supplementation for 8 weeks
Mean corpuscular hemoglobin
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from hemoglobin mass and erythrocyte count
Change from baseline after supplementation for 8 weeks
Mean corpuscular hemoglobin concentration
Time Frame: Change from baseline after supplementation for 8 weeks
Calculated from hemoglobin divided by hematocrit
Change from baseline after supplementation for 8 weeks
Reticulocyte count
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative flow cytometry
Change from baseline after supplementation for 8 weeks
Retinol binding protein, serum
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative nephelometry
Change from baseline after supplementation for 8 weeks
Retinol binding protein, urine
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative nephelometry
Change from baseline after supplementation for 8 weeks
Urine creatinine
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative spectrophotometry
Change from baseline after supplementation for 8 weeks
Serum creatinine
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative spectrophotometry
Change from baseline after supplementation for 8 weeks
Serum alanine aminotransferase
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative enzymatic assay
Change from baseline after supplementation for 8 weeks
Serum aspartate aminotransferase
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative enzymatic assay
Change from baseline after supplementation for 8 weeks
Serum gamma glutamyltransferase
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative enzymatic assay
Change from baseline after supplementation for 8 weeks
Serum alkaline phosphatase
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative enzymatic assay
Change from baseline after supplementation for 8 weeks
Serum bilirubin
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative quantitative spectrophotometry
Change from baseline after supplementation for 8 weeks
High-sensitivity c-reactive protein
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative quantitative immunoturbidimetry
Change from baseline after supplementation for 8 weeks
Tumor necrosis factor alpha
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative quantitative multiplex bead assay
Change from baseline after supplementation for 8 weeks
White blood cell count
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through automated cell count
Change from baseline after supplementation for 8 weeks
White blood cell differential
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through automated cell count
Change from baseline after supplementation for 8 weeks
Lymphocyte subtypes
Time Frame: Change from baseline after supplementation for 8 weeks
Direct measurement through quantitative flow cytometry
Change from baseline after supplementation for 8 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Total body vitamin A status via Stable Isotope Dilution
Time Frame: Change from baseline after supplementation for 8 weeks
compartmental modeling of [13C10]-retinyl acetate, measured by high performance liquid chromatography/mass spectroscopy
Change from baseline after supplementation for 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital of Philadelphia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Penn State University
Newcastle University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 2, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 1, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 16, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 16, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13-010081

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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