Individuals at Risk of Zinc Deficiency Clinical Trial
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
| Verified date | March 2018 |
| Source | London School of Hygiene and Tropical Medicine |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Completed |
| Enrollment | 26 |
| Est. completion date | December 27, 2017 |
| Est. primary completion date | July 19, 2017 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Months to 23 Months |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Gambia | Keneba Clinic | Kiang |
| Lead Sponsor | Collaborator |
|---|---|
| London School of Hygiene and Tropical Medicine | University of California, Davis |
Gambia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Fractional absorption of zinc | 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. | 10 days | |
| Secondary | Total absorption of zinc | Total absorption of zinc is estimated by multiplying fractional absorption of zinc by dietary zinc intake. | 10 days |