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Determination of Pre-Absorptive Dissociation of Zinc From a Zinc Amino Acid Complex in Healthy Men

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ClinicalTrials.gov Identifier: NCT03934346
Recruitment Status : Completed
First Posted : May 1, 2019
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
UCSF Benioff Children's Hospital Oakland

Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date January 22, 2020
Actual Study Start Date  ICMJE June 10, 2019
Actual Primary Completion Date December 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Zinc Transport Curve [ Time Frame: 2 weeks ]
    The saturable zinc transport curve determined by fitting the zinc absorption data to the Hill transport equation
  • Dissociated Amino Acid Zinc [ Time Frame: 2 weeks ]
    Amount of zinc dissociated from the ZnAA prior to absorption
Original Primary Outcome Measures  ICMJE Same as current
Change History
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 Determination of Pre-Absorptive Dissociation of Zinc From a Zinc Amino Acid Complex in Healthy Men
Official Title  ICMJE Determination of Pre-Absorptive Dissociation of Zinc From a Zinc Amino Acid Complex in Healthy Men
Brief Summary Zinc may be absorbed from diet via zinc transporter mediated pathways, or, when coupled with amino acids, via amino acid transporter pathways. When zinc is coupled with amino acids in diet, it may dissociate from those amino acids in the acidic environment of the stomach prior to entering the small intestine. An experimentally-determined value for any pre-absorptive dissociation of zinc from a zinc amino acid complex (ZnAA) is necessary for the accurate compartmental modeling of zinc metabolism when provided as ZnAA compared with ionic zinc, which the investigators will perform in a future study. The current study will allow us to determine the dissociation of zinc from ZnAA, while serving as a pilot test of a novel technique to determine for the first time an individual's zinc transport kinetics.
Detailed Description

An experimentally-determined value for any pre-absorptive dissociation of zinc from ZnAA is necessary for the accurate compartmental modeling of zinc metabolism when provided as ZnAA compared with zinc chloride, which the investigators will perform in a future study.

The current study will allow us to determine the pre-absorptive dissociation of zinc from ZnAA, while serving as a pilot test of a novel technique to determine for the first time an individual's zinc transport kinetics. Since zinc absorption kinetics follow a saturable process, the zinc transport maximum (Tr_max) and transport rate (K_Tr) can be determined by fitting Hill transport equation to measurements of absorbed zinc at 3 or more levels of zinc intake (mg zinc/d):

Total Absorbed Zinc (TAZ) = (Zinc Intake * Tr_max) / (Zinc Intake + K_Tr)

Although population data have been used to estimate zinc transport kinetics (Tran, et al. AJCN 2004), Tr_max and K_tr have never been determined in individual subjects. The investigators plan to determine the fractional zinc absorption (FZA) from multiple levels of dietary zinc in rapid succession (Chung, et al. AJCN 2004) and, therefore, estimate an individual's transport maximum and rate, Tr_max and K_Tr. Once Tr_max and K_Tr are known, the FZA can be used to determine an unknown zinc intake from zinc chloride and any zinc dissociated from the ZnAA complex using the following equation:

Zinc Intake = (Tr_max / FZA) - K_Tr

Since zinc that dissociates from the ZnAA complex will compete for absorption with the inorganic zinc stable isotopic oral tracer (70-zinc chloride), reducing the amount of that tracer absorbed, the investigators can therefore determine the total zinc intake (the sum of the known zinc in the controlled study diet and the unknown quantity of zinc dissociated from ZnAA pre-absorption) based on the transport kinetics (FZA, Tr_max and KTr).

In other words, for the meal with added ZnAA, the zinc intake is the sum of the zinc in the test meal (3.6 mg zinc and 0.4 mg 70-Zn tracer) and the zinc that dissociates from the ZnAA complex pre-absorption. Since the intact ZnAA (i.e. that zinc that does not dissociate pre-absorption from the ZnAA complex) is absorbed by a different transport mechanism (Sauer, et al. Biometals 2017), it does not compete with the stable isotope tracer for absorption via zinc cation transporters and is, therefore, not part of the "zinc intake" for the purpose of these calculations.

If the hypothesized 20% dissociation is correct (i.e. 3 mg zinc dissociated from an initial 15 mg ZnAA), the total amount of ionic zinc will be 7 mg (the 3.6 mg base diet, 0.4 mg zinc stable isotope tracer, and 3 mg dissociated zinc), and the FZA will therefore be the same as that from a 7 mg test diet (the 3.6 mg base diet, 0.4 mg zinc tracer, and 3 mg zinc as zinc chloride).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Nonlinear regression of fractional zinc absorption from 3 test diets using the Hill transport equation, and determination of an unknown amount of zinc based on fractional absorption from a single test diet. Order of the four test diets is randomized, with the constraint that the same oral zinc stable isotope tracer is not given on consecutive days.
Masking: None (Open Label)
Masking Description:
Subjects are not informed of the amount of zinc in each test diet, or the order of the diets. The basic foods making up the test diets are identical in appearance and amount on each of the oral zinc stable isotope tracer days, so there is no way for the subject to distinguish any differences in the amount or form of zinc given.
Primary Purpose: Basic Science
Condition  ICMJE Fractional Zinc Absorption
Intervention  ICMJE Other: Zinc amino acid complex
Zinc in the form of a Zinc Amino Acid Complex (ZnAA) is provided with a test diet, and the amount of zinc that dissociates from the ZnAA and is thus absorbed via an ionic zinc transport pathway is determined based on the Hill transport kinetics for the respective subject.
Study Arms  ICMJE Zinc transport kinetics
Three different amounts of dietary zinc are used in the creation of a standard curve for determining zinc absorption kinetics: 4 mg, 7 mg, and 15 mg of zinc.
Intervention: Other: Zinc amino acid complex
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: January 21, 2020)
13
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
10
Actual Study Completion Date  ICMJE December 16, 2019
Actual Primary Completion Date December 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Apparently healthy men
  • Body mass index between 18 and 30 kg/m2
  • Willing to eat only the foods provided by the study for a 2 week period

Exclusion Criteria:

  • Those reporting any chronic or acute diseases, food allergies, smoking or alcohol abuse
  • Use of illicit drugs; regular consumption of medications, micronutrient supplements, or both
  • Vegetarians, or those unable to eat meat, are also excluded since the foods for the study contain meat
  • Unable to refrain from taking medications during the study period
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03934346
Other Study ID Numbers  ICMJE 2019-001
Has Data Monitoring Committee Yes
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 Not Provided
Responsible Party UCSF Benioff Children's Hospital Oakland
Study Sponsor  ICMJE UCSF Benioff Children's Hospital Oakland
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew G Hall, Ph.D. UCSF Benioff Children's Hospital Oakland
PRS Account UCSF Benioff Children's Hospital Oakland
Verification Date January 2020

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