Lao Zinc Study: Effects of Two Forms of Daily Preventive Zinc Versus Therapeutic Zinc Supplementation

January 4, 2022 updated by: University of California, Davis

Lao Zinc Study: The Effects of Two Forms of Daily Preventive Zinc Supplementation Versus Therapeutic Zinc Supplementation for Diarrhea on Young Children's Physical Growth and Risk of New Episodes of Diarrhea

The study will be conducted as a community-based, randomized, placebo-controlled, trial with four study groups. The overall objective of the study is to determine the optimal method for delivering zinc to young children, both for the prevention of zinc deficiency and treatment of diarrhea. In particular, the investigators plan to compare the impact on physical growth, morbidity, micronutrient status, immune function, environmental enteric dysfunction, parasite burden and hair cortisol concentration of: 1) daily preventive zinc supplementation as a micronutrient powder (MNP); 2) placebo powders; 3) daily preventive zinc supplementation as dispersible tablets; 4) therapeutic zinc supplementation as dispersible tablets given in relation to episodes of diarrhea.

In addition to the major outcomes mentioned above, the investigators will monitor adherence to the interventions, neuro-behavioral development, and the occurrence of any adverse events.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Zinc is an essential nutrient that is required for children's normal growth and resistance to infections, including diarrhea and pneumonia, two major causes of child mortality. Current strategies for controlling the growth and infection-related complications of zinc deficiency include: 1) daily or weekly preventive zinc supplementation, and 2) therapeutic zinc supplementation for 10-14 days in relation to episodes of diarrhea. Information is needed on the relative impact of these intervention strategies on children's growth and risk of new episodes of diarrhea (and other infections).

Preventive zinc supplements can be delivered either as a single nutrient (zinc) supplement or as a multiple micronutrient (MMN) supplement, such as micronutrient powders (MNP) added to young children's complementary food. Available research indicates that zinc delivered in MNP at the currently recommended dose (4.1-5 mg/d) has not had a measurable impact on zinc-related functional outcomes, like growth and prevention of infection. Moreover, some studies of MMN supplements have detected a greater incidence of diarrhea in the MMN group than in the non-intervention or placebo control groups. Thus, despite the beneficial effects of MNP on prevention of anemia and enhancing iron status, questions have been raised about the desirability of providing zinc in MNP (containing iron and other nutrients) versus a single nutrient formulation offered between meals. For these reasons, the present study is designed to compare both the zinc delivery plan (i.e., preventive versus therapeutic supplementation) as well as the form of delivering zinc (i.e., as a dispersible tablet given between meals or as a MNP given with meals) and to permit assessment of any adverse effects of MNP on the incidence of diarrhea.

The study will be conducted as a community-based, randomized, placebo-controlled trial with four study groups in rural communities of Khammouane Province in Central Lao PDR.

The project team will enroll a total of ~3,400 children whose ages will range from 6-23 months. Children will be randomly assigned to one of four study group: 1) preventive zinc supplementation provided as LI-MNP plus ORS and placebo tablets for treatment of diarrhea; 2) placebo preventive supplementation provided as placebo powder plus ORS and placebo tablets for diarrhea ; 3) preventive zinc supplementation provided as dispersible zinc tablets (containing 7 mg zinc, to be given between meals) plus ORS and placebo tablets for diarrhea; and 4) therapeutic zinc supplementation provided as dispersible tablets (containing 20 mg zinc) for diarrhea plus ORS and placebo preventive tablets.

The major outcomes that will be monitored include adherence to the interventions; physical growth; incidence, duration and severity of episodes of diarrhea; changes in MN status; immune function; environmental enteric dysfunction; parasite burden; hair cortisol concentration; neuro-behavioral development; and the occurrence of any adverse events.

Study Type

Interventional

Enrollment (Actual)

3433

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 1 year (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed informed consent from at least one parent or primary caregiver
  • Age 6-23 months initially
  • Permanent resident of study area
  • Planned availability during the period of the study
  • Acceptance of home visitors

Exclusion Criteria:

  • Weight-for-height z-score (WHZ) <-3Z with respect to WHO 2006 standards
  • Presence of bipedal edema
  • Severe illness warranting hospital referral
  • Congenital abnormalities potentially interfering with growth
  • Chronic medical condition (e.g. malignancy) requiring frequent medical attention
  • Known HIV infection of index child or child's mother
  • Hemoglobin <70 g/L
  • Currently consuming zinc supplements
  • Current participation in any other clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: micronutrient powder (MNP)
preventive zinc supplements provided as MNP (containing 10 mg zinc and 14 other nutrients, including 6 mg iron, 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg vitamin B1, 0.5 mg vitamin B2, 6 mg niacin, 0.5 mg vitamin B6, 0.9 μg vitamin B12, and 150 μg folate,) plus ORS and therapeutic placebo supplements for diarrhea
Dietary supplement: MNP
MNP containing containing 10 mg zinc and 14 other nutrients, including 6 mg iron, 0.56 mg copper, 17 μg selenium, 90 μg iodine, 400 μg RE vitamin A, 5 μg vitamin D, 5 mg vitamin E, 30 mg ascorbic acid, 0.5 mg vitamin B1, 0.5 mg vitamin B2, 6 mg niacin, 0.5 mg vitamin B6, 0.9 μg vitamin B12, and 150 μg folate
Dietary supplement: therapeutic placebo supplement
dispersible placebo tablet for 10 days during diarrhea episodes
PLACEBO_COMPARATOR: placebo powder
placebo powder plus ORS and therapeutic placebo supplements for diarrhea
Dietary supplement: therapeutic placebo supplement
dispersible placebo tablet for 10 days during diarrhea episodes
Dietary supplement: placebo powder
placebo powder
ACTIVE_COMPARATOR: preventive zinc supplements
preventive zinc supplements provided as dispersible zinc tablets (containing 7 mg zinc, to be given between meals) plus ORS and therapeutic placebo supplements for diarrhea
Dietary supplement: therapeutic placebo supplement
dispersible placebo tablet for 10 days during diarrhea episodes
Dietary supplement: preventive zinc supplement
7 mg zinc daily as dispersible tablet
ACTIVE_COMPARATOR: therapeutic zinc supplements
preventive placebo supplements provided as dispersible tablets plus ORS and dispersible therapeutic zinc tablets (containing 20 mg zinc) for diarrhea
Dietary supplement: therapeutic zinc supplement
20 mg zinc per day for 10 days during diarrhea episodes, as dispersible tablet
Dietary supplement: preventive placebo supplement
dispersible daily placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in length and length-for-age Z-score
Time Frame: 36 weeks
36 weeks
Change in weight and weight-for-age Z-score
Time Frame: 36 weeks
36 weeks
Incidence of diarrhea
Time Frame: 36 weeks
36 weeks
Change in hemoglobin concentration
Time Frame: 32 weeks
32 weeks
Change in micronutrient status
Time Frame: 32 weeks
plasma zinc, ferritin, transferrin receptor; and retinol binding protein (RBP) concentrations, measured in a subsample of 560 participants, and controlling for the presence of elevated acute phase protein
32 weeks
Innate and adaptive immune defense
Time Frame: 32 weeks
production of cytokines by cultures of peripheral blood white blood cells; and change in concentrations of naïve and memory CD4 and CD8 T-cells and regulatory (Treg) T-cells in a sub-set of 500 children
32 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mid-upper circumference
Time Frame: 36 weeks
36 weeks
Achievement of gross motor developmental milestones
Time Frame: after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
Gross motor developmental milestones as recommended by the World Health Organization include: sitting without support, crawling, standing with assistance, walking with assistance, standing alone, walking alone
after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
Change in stool calprotectin concentration
Time Frame: 36 weeks
36 weeks
Change in stool neopterin concentration
Time Frame: 36 weeks
36 weeks
Change in hair cortisol concentration
Time Frame: 36 weeks
36 weeks
Intestinal protozoa parasite infection
Time Frame: 36 weeks
Intestinal protozoan infections will be assessed by a modified formalin-ethyl acetate concentration technique
36 weeks
Helminths parasite infection
Time Frame: 36 weeks
Helminth parasite infections will be assessed using duplicate Kato-Katz thick smears
36 weeks
Acute and chronic sleep pattern
Time Frame: after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
Assessed by Brief Infant Child Sleep Questionnaire
after 4, 8, 12, 16, 20, 24, 32 and 36 weeks
B-vitamin status
Time Frame: 36 weeks
erythrocyte thiamine diphosphate, plasma folate and B12 concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) measured in a randomly selected sub-sample of 260 children (MNP and control group only)
36 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of serious adverse events
Time Frame: 36 weeks
Serious adverse events, including death and required overnight stay in a health facility
36 weeks
Incidence of any non-serious adverse events
Time Frame: 36 weeks
non-serious adverse events that may be detected retrospectively, such as the incidence of diarrhea, vomiting, etc., based on the results of morbidity surveillance
36 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Collaborators

University of British Columbia
Khon Kaen University
USDA, Western Human Nutrition Research Center
The Mathile Institute for the Advancement of Human Nutrition
Nutrition International
Lao Tropical and Public Health Institute, Lao PDR

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (ACTUAL)

May 1, 2017

Study Completion (ACTUAL)

July 1, 2017

Study Registration Dates

First Submitted

February 9, 2015

First Submitted That Met QC Criteria

April 28, 2015

First Posted (ESTIMATE)

April 29, 2015

Study Record Updates

Last Update Posted (ACTUAL)

January 20, 2022

Last Update Submitted That Met QC Criteria

January 4, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 626187
  • 10-1347-UCALIF-07 (OTHER: Other)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The complete de-identified dataset will be made publicly available within 3 years after completion of data collection. Associated data dictionaries will be made available along with the datasets.

IPD Sharing Time Frame

Summer 2020

IPD Sharing Access Criteria

Publicly available

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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