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Trial record 1 of 1 for:    NCT02668133
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Zinc Absorption From SQ-LNS With and Without Phytase

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 by Medical Research Council Unit, The Gambia
Sponsor:
Collaborator:
University of California, Davis
Information provided by (Responsible Party):
Medical Research Council Unit, The Gambia
ClinicalTrials.gov Identifier:
NCT02668133
First received: January 21, 2016
Last updated: May 5, 2017
Last verified: May 2017
  Purpose

Background: Community based-intervention trials conducted among infants and young children in low- and middle-income countries have found that zinc supplementation of young children (in the form of liquid supplements or dispersible tablets) increases linear growth and weight gain, and reduces the prevalence of diarrhea and respiratory infections, and lowers all-cause mortality. Aside from supplements, additional dietary zinc can also be provided through "home-fortification" of complementary foods with small-quantity lipid-based nutrient supplements (SQ-LNS; 20g/d), which are typically formulated as a peanut-based paste enriched with a vitamin and mineral complex containing 8 mg elemental zinc (as ZnSO4). However, the efficacy of LNS as a delivery vehicle for preventive zinc supplementation remains uncertain. Two recent studies, which provided LNS containing 4-10 mg Zn daily for 6-9 months found no significant differences in plasma zinc concentrations at the end of the intervention period compared to placebo.

This lack of response may be due to the reduced absorption of zinc when it is part of a complex food matrix and provided with cereal-based meals; both SQ-LNS and cereal grains contain moderate to high concentrations of phytate, the main dietary factor known to substantially reduce zinc absorption. The addition of exogenous phytases is an efficacious strategy to reduce the phytate content of foods, and increase the bioavailability of dietary zinc; however, the efficacy of this approach has not yet been demonstrated for SQ-LNS.

Objective: The overall objective of the study is to assess the efficacy of adding exogenous phytase to SQ-LNS by investigating intra-individual differences in the fractional absorption of zinc (FAZ) among children who receive additional dietary zinc (8 mg/d) from SQ-LNS with or without phytase.

Trial approach: The study will be a double-blind randomized controlled clinical trial, designed to permit within-child comparisons of zinc absorption from SQ-LNS, with or without exogenous phytase, by using the triple stable-isotope ratio tracer technique. The clinical study will enroll 34 children between the ages of 18-23 months. The main outcome of interest is the intra-individual difference in the FAZ from porridge-based meals containing SQ-LNS with and without phytase. Up to an` additional 36 children will be enrolled in a pilot feeding study to determine portion sizes of study meals.

Trial setting: Keneba, The Gambia

Trial interventions:

The SQ-LNS (20g) used in this study will be provided by Nutriset, S.A.S. The exogenous phytase (DSM phytase Tolerase 20000G) is derived from Aspergillus niger; phytase will be added to the SQ-LNS during the production phase, and will be enzymatically active in vivo at the time of consumption.

Feeding Protocol and Study Diet: The study diet for the 2day absorption study will consist of the following: 1) Two stable-isotope labeled test meals per day (porridge made from locally procured non-fermented cereal, mixed with 10 g of SQ-LNS), with children randomized to receive either SQ-LNS with phytase or SQ-LNS without phytase on the first day and the alternative product on the second; 2) One additional standardized meal per day (e.g. rice with sauce); 3) Low-zinc, low-phytate food (e.g. bananas) consumed ad libitum if requested (with the exception of 1 hour before and 2 hours after each test meal). Children will be fed by their caregivers under supervision by a study fieldworker. The SQ-LNS product (without phytase) will be provided to children twice per day for one day prior to the start of the stable isotope absorption studies, in order to habituate children to the study diet and location. Children will attend the study clinic daily for four days and will be enrolled in the study for a total of ten days.

Zinc absorption studies: The FAZ of zinc will be measured by a triple-isotope tracer ratio technique, using orally administered extrinsic labels (Zn-67 and Zn-70) and intravenous Zn-68. Urine samples, collected pre- and post-isotope administration (d 1, 5-9) will be analyzed for zinc isotope ratios by ICP-MS. FAZ will be calculated based on the mean isotopic ratios obtained from the enriched urine samples, and based on the tracer:tracee ratio method. TAZ will be calculated by multiplying FAZ by total zinc intake from the test meals.

Data Collection: The following information will be collected from each subject: brief medical history; physical examination; weight and height; daily morbidity and pre-intervention blood sampling for hemoglobin, complete blood count and plasma zinc concentration, malaria and systemic inflammation (C-reactive protein and α-1-acid glycoprotein).


Condition Intervention
Individuals at Risk of Zinc Deficiency
Dietary Supplement: the nutritional supplement to be used in this trial is a SQ-LNS
Dietary Supplement: lipid-based nutrient supplement (SQ-LNS) with phytase
Dietary Supplement: 0.9 mg isotopically enriched 67Zn,0.30 mg isotopically enriched 70Zn, 0.60 mg non-enriched zinc
Dietary Supplement: 1 mg isotopically enriched 68Zn

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Other
Official Title: Efficacy of Exogenous Phytase Added to Small Quantity Lipid Nutrient Supplements (SQ-LNS) on the Fractional and Total Absorption of Zinc Among Young Children in the Gambia: A Double-blind Randomized Controlled Trial With a Cross-over Design

Resource links provided by NLM:


Further study details as provided by Medical Research Council Unit, The Gambia:

Primary Outcome Measures:
  • Fractional absorption of zinc [ Time Frame: 10 days ]
    Fractional absorption of zinc is estimated using the triple zinc stable isotope tracer ratio technique. 67Zn and 70Zn are administered orally and 68Zn is administered intravenously. The urinary enrichment of the three isotopes is measured over 5 days (ICP-MS) and tracer:tracee ratios are calculated.


Secondary Outcome Measures:
  • Total absorption of zinc [ Time Frame: 10 days ]
    Total absorption of zinc is estimated by multiplying fractional absorption of zinc by dietary zinc intake.


Estimated Enrollment: 50
Actual Study Start Date: April 18, 2017
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: lipid-based nutrient supplement SQ-LNS

• Small quantity lipid nutrient supplement SQ-LNS containing 6 mg iron and 8 mg zinc per 20 g sachet (per day) 0.9 mg isotopically enriched 67Zn,0.30 mg isotopically enriched 70Zn, 0.60 mg non-enriched zinc delivered orally in sugar solution

1 mg isotopically enriched 68Zn intravenously

Dietary Supplement: the nutritional supplement to be used in this trial is a SQ-LNS
Small quantity lipid nutrient supplement (SQ-LNS) containing 6 mg iron and 8 mg zinc per 20 g sachet (per day
Dietary Supplement: 0.9 mg isotopically enriched 67Zn,0.30 mg isotopically enriched 70Zn, 0.60 mg non-enriched zinc
delivered orally in sugar solution
Dietary Supplement: 1 mg isotopically enriched 68Zn
administered intravenously
Experimental: lipid-based nutrient supplement SQ-LNS with phytase

• Small quantity lipid nutrient supplement SQ-LNS containing 6 mg iron and 8 mg zinc per 20 g sachet (per day). Exogenous phytase (projected concentration ~500 FTU/20 g SQ-LNS added during manufacturing 0.9 mg isotopically enriched 67Zn,0.30 mg isotopically enriched 70Zn, 0.60 mg non-enriched zinc delivered orally in sugar solution

1 mg isotopically enriched 68Zn intravenously

Dietary Supplement: lipid-based nutrient supplement (SQ-LNS) with phytase
• Small quantity lipid nutrient supplement (SQ-LNS) containing 6 mg iron and 8 mg zinc per 20 g sachet (per day). Exogenous phytase (projected concentration ~500 FTU/20 g SQ-LNS) added during manufacturing
Dietary Supplement: 0.9 mg isotopically enriched 67Zn,0.30 mg isotopically enriched 70Zn, 0.60 mg non-enriched zinc
delivered orally in sugar solution
Dietary Supplement: 1 mg isotopically enriched 68Zn
administered intravenously

  Eligibility

Ages Eligible for Study:   18 Months to 23 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Signed informed consent from at least one parent, including consent for samples to be shipped outside of The Gambia
  • Age 18-23 months
  • non-breast feeding children and consumption of coos porridge
  • Previous consumption of peanut based products with no known adverse reaction

Exclusion Criteria:

  • Weight-for-height z-score (WHZ) <-3 Z with respect to WHO 2006 standards*
  • Presence of bipedal oedema
  • Severe illness warranting hospital referral
  • Congenital abnormalities potentially interfering with micronutrient metabolism
  • Chronic medical condition (e.g. malignancy) requiring frequent medical attention
  • Known HIV infection of index child or child's mother
  • Currently consuming vitamin or mineral supplements or zinc- or iron-fortified infant formulas/foods
  • Diarrhoea (>3 liquid or semi-liquid stools per day) within the past 7 days
  • Symptomatic acute or chronic febrile infection within the past 7 days
  • Hemoglobin < 70 g/L*
  • Positive rapid diagnostic test for malaria antigenemia (HRP2)* * Exclusion criteria for main metabolic study only (not criteria for the pilot feeding study, as anthropometric and biochemical data will not be collected
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02668133

Contacts
Contact: Sarah J Burke Zyba, BA +220-2524011 sjburke@ucdavis.edu
Contact: Vivat Thomas-Njie +220-4495442-6 ext 2202 vthomas@mrc.gm

Locations
Gambia
Keneba Clinic Recruiting
Kiang, Gambia
Contact: Rowena Neville, MD    +220-4495    rneville@mrc.gm   
Contact: Sarah J Burke Zyba, BA    +220-2524011      
Principal Investigator: Andrew Prentice, PhD         
Sponsors and Collaborators
Medical Research Council Unit, The Gambia
University of California, Davis
Investigators
Principal Investigator: Andrew Prentice, PhD Medical Research Council The Gambia
  More Information

Responsible Party: Medical Research Council Unit, The Gambia
ClinicalTrials.gov Identifier: NCT02668133     History of Changes
Other Study ID Numbers: SCC 1420
Study First Received: January 21, 2016
Last Updated: May 5, 2017
Individual Participant Data  
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Medical Research Council Unit, The Gambia:
zinc deficiency
zinc absorption

Additional relevant MeSH terms:
Zinc
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2017