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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

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.

Condition or disease Intervention/treatment Phase
Vitamin A Deficiency Dietary Supplement: β-cryptoxanthin Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
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
Official Title: 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
Actual Study Start Date : April 1, 2019
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin A

Arm Intervention/treatment
Experimental: Phase 1
Determination absorption and bioconversion kinetics of [13C14]β-cryptoxanthin and provide external validation for single-sample prediction methods.
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

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.
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




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04153968


Contacts
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Contact: Anthony Oxley, PhD 0191 208 1403 anthony.oxley@ncl.ac.uk
Contact: Georg Lietz, PhD 0191 208 6893 georg.lietz@ncl.ac.uk

Locations
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United Kingdom
Newcastle University Recruiting
Newcastle Upon Tyne, Tyne & Wear, United Kingdom, NE2 4HH
Contact: Anthony Oxley, PhD    0191 208 1403    anthony.oxley@ncl.ac.uk   
Principal Investigator: Georg Lietz, PhD         
Sponsors and Collaborators
Newcastle University
International Food Policy Research Institute
Penn State University

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Responsible Party: Newcastle University
ClinicalTrials.gov Identifier: NCT04153968     History of Changes
Other Study ID Numbers: BH183438
First Posted: November 6, 2019    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Eye Diseases
Night Blindness
Vitamin A Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vision Disorders
Acetic Acid
Retinol acetate
Carotenoids
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Adjuvants, Immunologic
Immunologic Factors
Anticarcinogenic Agents
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents