Lao Zinc Study: Effects of Two Forms of Daily Preventive Zinc Versus Therapeutic Zinc Supplementation
Condition: Diarrhea
MeSH terms: Diarrhea
Study type: Interventional

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.
    

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.
    

Intervention name(s): MNP; preventive zinc supplement; therapeutic zinc supplement; preventive placebo supplement; therapeutic placebo supplement; placebo powder
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 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; 7 mg zinc daily as dispersible tablet; 20 mg zinc per day for 10 days during diarrhea episodes, as dispersible tablet; dispersible daily placebo tablet; dispersible placebo tablet for 10 days during diarrhea episodes; placebo powder
Intervention MeSH terms: Zinc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: growth; plasma zinc concentration