Oral Zinc for the Treatment of Acute Diarrhea in US Children
Condition: Diarrhea; Gastroenteritis
MeSH terms: Gastroenteritis; Diarrhea
Study type: Interventional

Summary: 
      Diarrheal diseases are the third leading cause of mortality in the world, with nearly 2
      million deaths annually among children under age 5 years. Several clinical trials of oral
      zinc supplementation performed in developing country populations have confirmed this
      nutrient's efficacy in reducing the severity and frequency of diarrhea. The World Health
      Organization (WHO) has recommended global use of zinc supplementation in all children with
      diarrhea despite little or no data from trials in industrialized/developed settings. In the
      United States over 4 million children suffer annually from diarrheal illness. Although
      mortality is not a significant factor in U.S. cases, 75% of all cases present to medical care
      resulting in over 200,000 hospitalizations annually for diarrhea. This has significant impact
      on U.S. healthcare costs, with an average of $391 per outpatient treatment and $2,549 per
      inpatient treatment spent on each episode of acute diarrheal illness. The goal of this study
      is to evaluate the effectiveness of oral zinc in decreasing the duration of diarrhea in
      children treated as outpatients and in decreasing the duration of hospitalization in children
      treated as inpatients in an industrialized country. The results of this study promise to have
      a substantial impact on the management of a common pediatric health problem, and could
      conceivably affect direct and indirect healthcare costs to society.
    

Detailed description: 
      In developing countries, diarrheal diseases are a leading cause of childhood morbidity and
      mortality. In the United States an estimated 4.67 million children per year suffer from
      gastroenteritis with a diarrheal component, impacting the delivery and cost of healthcare.
      Seventy-five percent of these children are brought to physician care across a range of
      settings from clinics to emergency departments. Children less than five years of age average
      1.3 - 2.5 episodes per year, with 1.4% of those children requiring hospitalization annually.
      This results in an estimated 209,000 hospitalizations yearly for gastroenteritis. The impact
      of acute gastrointestinal disease can be felt in the developed world, including the United
      States, as cost attributed to hospitalization and productivity lost. Attempts at treating
      gastroenteritis have included Oral Rehydration Solution (ORS), introduced 30 years ago by the
      WHO, which continues to provide a safe and effective way to maintain hydration during acute
      illness. ORS, however, does not reduce the volume or frequency of stool output in diarrhea.
      The anti-diarrheal medication loperamide (Imodium®) was commonly used in children until
      reports of serious adverse reactions caused its use to fall out of favor. There are no other
      medications or supplements available to specifically treat the diarrheal component of
      gastroenteritis and studies have shown that adherence to treatment recommendations regarding
      fluid therapy is poor because care givers want to reduce duration of illness as opposed to
      supporting children through the natural course of the disease. The desire to relieve
      diarrheal symptoms often leads care givers to seek antibiotics during a time of rising
      antibiotic resistance, as well as other treatments with no proven efficacy.

      Zinc is an essential trace element for humans. Its physiologic roles are seen throughout the
      body as a critical cofactor for enzymatic reactions; most notable are its actions in the
      gastrointestinal (GI) tract. Zinc is an important component of brush border enzymatic
      activity which promotes gastrointestinal absorption, it regulates water/electrolyte transport
      at the cellular level, and it enhances the repair of the intestinal mucosa by bolstering
      immune function. Over the past 10-15 years, there have been more than a dozen randomized
      controlled trials of zinc supplementation performed in children living in developing
      countries that have reported improvements in the duration and severity of diarrhea when
      compared to placebo in a variety of in- and outpatient settings. The majority of zinc trials
      were conducted in countries at high risk of zinc deficiency, but those conducted at medium
      risk showed similar effect on duration and severity. When stratified across all nutritional
      groups based on serum zinc levels a significant effect was seen compared to placebo despite
      baseline zinc level, with no occurrence of serious adverse reaction in any group. Given these
      results, the WHO has endorsed zinc supplementation for all children with acute diarrhea,
      despite the lack of data from similarly designed studies in industrialized/developed
      settings.
    

Intervention name(s): Zinc Sulfate; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): For children ages 6month to 1 year, 12.5mg orally daily for 14 days mixed in 60 mL of fluid.
For children aged 1 year and above 25mg orally daily for 14 days mixed in 60 mL of fluid.; Effervescent oral capsules with similar taste to treatment drug Zinc Sulfate is provided to each patient randomized to the placebo arms of the study
Other intervention name(s): Treatment; Placebo
Intervention MeSH terms: Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Diarrhea; Gastroenteritis; Zinc Supplementation