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

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ClinicalTrials.gov Identifier: NCT02428647
Recruitment Status : Completed
First Posted : April 29, 2015
Last Update Posted : July 13, 2018
Sponsor:
Collaborators:
National Institute of Public Health, Lao PDR
USDA, Western Human Nutrition Research Center
University of British Columbia
Khon Kaen University
Micronutrient Initiative
The Mathile Institute for the Advancement of Human Nutrition
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Diarrhea Dietary Supplement: MNP Dietary Supplement: preventive zinc supplement Dietary Supplement: therapeutic zinc supplement Dietary Supplement: preventive placebo supplement Dietary Supplement: therapeutic placebo supplement Dietary Supplement: placebo powder Not Applicable

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  (Clinical Trial)
Actual Enrollment : 3433 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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
Study Start Date : September 2015
Actual Primary Completion Date : May 2017
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diarrhea

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: preventive zinc supplement
7 mg zinc daily as dispersible tablet

Dietary Supplement: therapeutic placebo supplement
dispersible placebo tablet for 10 days during diarrhea episodes

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




Primary Outcome Measures :
  1. Change in length and length-for-age Z-score [ Time Frame: 36 weeks ]
  2. Change in weight and weight-for-age Z-score [ Time Frame: 36 weeks ]
  3. Incidence of diarrhea [ Time Frame: 36 weeks ]
  4. Change in hemoglobin concentration [ Time Frame: 32 weeks ]
  5. 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

  6. 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


Secondary Outcome Measures :
  1. Change in mid-upper circumference [ Time Frame: 36 weeks ]
  2. 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

  3. Change in stool calprotectin concentration [ Time Frame: 36 weeks ]
  4. Change in stool neopterin concentration [ Time Frame: 36 weeks ]
  5. Change in hair cortisol concentration [ Time Frame: 36 weeks ]
  6. Intestinal protozoa parasite infection [ Time Frame: 36 weeks ]
    Intestinal protozoan infections will be assessed by a modified formalin-ethyl acetate concentration technique

  7. Helminths parasite infection [ Time Frame: 36 weeks ]
    Helminth parasite infections will be assessed using duplicate Kato-Katz thick smears

  8. 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


Other Outcome Measures:
  1. Incidence of serious adverse events [ Time Frame: 36 weeks ]
    Serious adverse events, including death and required overnight stay in a health facility

  2. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   6 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 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

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): NCT02428647


Locations
Lao People's Democratic Republic
National Institute of Public Health
Vientiane, Lao People's Democratic Republic
Sponsors and Collaborators
University of California, Davis
National Institute of Public Health, Lao PDR
USDA, Western Human Nutrition Research Center
University of British Columbia
Khon Kaen University
Micronutrient Initiative
The Mathile Institute for the Advancement of Human Nutrition
Investigators
Principal Investigator: Sonja Y Hess, PhD University of California, Davis

Publications of Results:
Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT02428647     History of Changes
Other Study ID Numbers: 626187
10-1347-UCALIF-07 ( Other Identifier: Other )
First Posted: April 29, 2015    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Summer 2020
Access Criteria: Publicly available
URL: https://osf.io/5bq9c/

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

Keywords provided by University of California, Davis:
growth
plasma zinc concentration

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Zinc
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs