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Bioefficacy of Beta-cryptoxanthin From Biofortified Maize (BIOCRYPT)

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ClinicalTrials.gov Identifier: NCT04153968
Recruitment Status : Recruiting
First Posted : November 6, 2019
Last Update Posted : November 6, 2019
Sponsor:
Collaborators:
International Food Policy Research Institute
Penn State University
Information provided by (Responsible Party):
Newcastle University

Tracking Information
First Submitted Date  ICMJE November 4, 2019
First Posted Date  ICMJE November 6, 2019
Last Update Posted Date November 6, 2019
Actual Study Start Date  ICMJE April 1, 2019
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2019)
Bioefficacy of β-cryptoxanthin [ Time Frame: Phase 1 = 91 days. Phase 2 = 22 days. ]
Plasma concentrations of [13C14]-β-cryptoxanthin, [13C7]-retinyl esters, and [13C7]-retinol.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bioefficacy of Beta-cryptoxanthin From Biofortified Maize
Official Title  ICMJE Determination of Relative Bioavailability, Bioconversion and Bioefficacy of β-cryptoxanthin in Comparison to β-carotene From Biofortified Maize and External Stable Isotopes Using Compartmental Modelling
Brief Summary Since no quantitative information currently exists on how effectively the pro-vitamin A carotenoid (pVAC) β-cryptoxanthin (βCX) is converted to vitamin A (VA) in humans, this proof of principle study aims to compare the efficacy of both βCX and β-carotene (βC) to yield VA from biofortified maize. This data is critical before the breeding strategy for biofortified maize is directed towards high βCX-containing varieties in order to reduce VA deficiency in low-income countries.
Detailed Description

Despite advances in reducing vitamin A (VA) deficiency worldwide, the prevalence remains highest and unchanged in sub-Saharan Africa and South Asia. Efficacy studies have demonstrated that increasing provitamin A carotenoid (pVAC) intake through consuming pVAC biofortified crops results in increased circulating β-carotene (βC) and VA body stores. It has also been shown that consumption of biofortified maize improved VA total body stores (TBS) as effectively as preformed VA supplementation, and significantly improved visual function in marginally VA deficient children. Despite the fact that βC is the primary focus of breeding programs for pVAC biofortified maize, there is convincing evidence that comparable dietary intakes of βC and β-cryptoxanthin (βCX) would result in 7-fold greater concentrations of βCX in blood.

The study is designed to determine for the first time the bioefficacy of βCX in comparison to βC in humans using state of the art isotope dilution techniques in combination with compartmental modelling. The project is conducted in two phases: Phase 1) the determination of best time points for assessment of βCX bioconversion, intestinal and postintestinal bioefficacy as well as quantifying TBS of VA in healthy volunteers; Phase 2) to test the bioefficacy of βCX and βC in maize by comparing a high βCX and low βC maize variety to a high βC and low βCX maize variety.

Phase 1 of the study involves 1 long study day (D0), where 10 ml of blood will be taken every 2 hours, via cannulation, for a total of 12 hours (70 ml of blood total). Subsequently, there are 13 followup visits on the mornings of Days 1, 2, 4, 7, 11, 14, 21, 28, 35, 49, 63, 77, and 91 where one 10 ml blood sample is taken.

Phase 2 of the study involves 2 whole days (D0 and D21) where approximately 10 ml of blood will be taken every 30-60 minutes, via cannulation, for a total of 8 hours (110 ml of blood total). Subsequently, there are 3 follow-up visits on the mornings of Days 1, 7, and 22 where one 10 ml blood sample is taken on each occasion.

In the mornings of the long/whole study days at either D0 or D21, participants will receive the muffin test meal before stable isotopes, dissolved in sunflower oil, are administered via oral pipette. At D0 or D21, the total dose of pVACs (labelled and unlabelled carotenoids) consumed in the muffin and oil is 3 mg alongside 0.4 mg of pre-formed VA.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
The study is designed in two phases to allow the research team to firstly determine the absorption and bioconversion kinetics of pure βCX and provide external validation for single-sample prediction methods. The second phase aims to test the bioavailability of both pVACs in maize by comparing a high βCX:βC variety to a low βCX:βC variety in combination with external [13C]-labelled pVACs.
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Vitamin A Deficiency
Intervention  ICMJE Dietary Supplement: β-cryptoxanthin

Phase 1:

2.0mg of [13C14]β-cryptoxanthin, 1.0mg of [13C10]β-carotene and 0.4mg [2H6]retinyl acetate are given in sunflower oil at Time 0.

Phase 2:

1.5mg of [13C14]β-cryptoxanthin, 0.75mg of [13C10]β-carotene, 0.4mg [2H6]retinyl acetate are given in sunflower oil along with 0.25mg β-carotene and 0.5mg β-cryptoxanthin from maize are given at Time 0.

Then, 0.75mg of [13C14]β-cryptoxanthin, 1.5mg of [13C10]β-carotene, and 0.4mg [2H6]retinyl acetate are given in sunflower oil along with 0.5mg β-carotene and 0.25mg β-cryptoxanthin from maize are given on day 21.

Other Name: β-carotene; retinyl acetate
Study Arms  ICMJE
  • Experimental: Phase 1
    Determination absorption and bioconversion kinetics of [13C14]β-cryptoxanthin and provide external validation for single-sample prediction methods.
    Intervention: Dietary Supplement: β-cryptoxanthin
  • Experimental: Phase 2
    Test the bioefficacy of provitamin A carotenoids (pVACs) in maize by comparing a high β-cryptoxanthin:β-carotene (βCX:βC) variety to a low βCX:βC variety in combination with external [13C]-labelled pVACs.
    Intervention: Dietary Supplement: β-cryptoxanthin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 4, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2020
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Healthy volunteers

Exclusion Criteria:

  • Females who are pregnant or lactating.
  • Not disclosing use and type of contraceptives.
  • Acute or chronic illness.
  • Concurrent participation in another study.
  • Unwillingness to discontinue personal nutritional supplements/vitamins.
  • Major food allergies/intolerance to study ingredients.
  • Previous history of anorexia or bulimia.
  • Inability to refrain from drinking alcohol when requested.
  • Fat mal-absorptive disorders or iron deficiency anaemia.
  • Dietary preformed vitamin A intake >600 µg/d.
  • BMI <20 and >29 kg/m2.
  • Smoking.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Anthony Oxley, PhD 0191 208 1403 anthony.oxley@ncl.ac.uk
Contact: Georg Lietz, PhD 0191 208 6893 georg.lietz@ncl.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04153968
Other Study ID Numbers  ICMJE BH183438
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Newcastle University
Study Sponsor  ICMJE Newcastle University
Collaborators  ICMJE
  • International Food Policy Research Institute
  • Penn State University
Investigators  ICMJE Not Provided
PRS Account Newcastle University
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP