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Oral Zinc for the Treatment of Acute Diarrhea in US Children

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Michelle Niescierenko, Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT01198587
First received: September 2, 2010
Last updated: June 21, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Diarrhea
Gastroenteritis
Drug: Zinc Sulfate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Randomized Placebo Controlled Trial of Oral Zinc for Children With Acute Diarrhea in a Developed Nation.

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • Duration of diarrhea in acute diarrheal illnesses in a developed nation while taking zinc or placebo. [ Time Frame: 14 days ] [ Designated as safety issue: No ]
    Patient's symptoms will be assessed over their 14 day study medication/placebo course.Symtpoms will be assessed daily by caregivers for 14 days and recorded on a symptom tracking chart which will be returned to study investigators on day 15 (last day of the study). Care givers will also receive follow up phone calls on days 2, 3, 5, 7, 10, 15 assessing symptoms. Outcome of all patients in study will be assessed at study conclusion in 2 years.

  • Length of hospitalization for children with diarrheal illness taking zinc or placebo. [ Time Frame: 14 days of study medication ] [ Designated as safety issue: No ]
    Time of discharge for patients admitted with diarrhea will be assessed during patient's 14 day course of zinc or placebo at the time they are discharged from the hospital. No further discharge information will be assessed. Entire study population will be assessed at the end of study period 2 years.


Secondary Outcome Measures:
  • Examine the potential cost benefits of supplementation with zinc in reducing number of work days lost, daycare days not attended and decrease in length of hospitalization [ Time Frame: after completion of study in 2 years time ] [ Designated as safety issue: No ]
  • Assess parent reporting reliability comparing survey responses to phone interview. [ Time Frame: Once trial is completed in 2 years time ] [ Designated as safety issue: No ]

Estimated Enrollment: 210
Study Start Date: November 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Outpatient
Outpatients with diarrhea will be randomized to either zinc or placebo to assess the effect on duration of diarrhea.
Drug: Zinc Sulfate

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.

Inpatient
Patients admitted to the hospital with diarrhea and dehydration will be randomized to zinc or placebo, duration of hospitalization will be assessed.
Drug: Zinc Sulfate

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.


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 (Immodium®) 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.

  Eligibility

Ages Eligible for Study:   6 Months to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Healthy Children with non-bloody diarrhea illness defined as loose or watery stools
  • Symptoms must be present for greater than 24 hours but less than 72 hours.
  • Comorbid conditions including; Asthma, Gastroesophageal reflux (unless followed by a Gastroenterologist), Mild speech, language, motor delays, Benign heart murmurs, Isolated atrial septal defect (ASD) or ventricular septal defect VSD, Epilepsy (unless developmentally delayed), Children born Prematurely between 33-37 weeks without long term sequelae, Repaired tetralogy of fallot (no cardiac issues for >6 months), Diabetes may be enrolled in the study.

Exclusion Criteria:

  • Children with symptoms less than 24 hours
  • Children with symptoms greater than 24 hours
  • Failure to thrive
  • G or J tube
  • Major surgery within last 3 months
  • Minor surgery (tonsillectomy, ear tubes, skin lesion removals etc) within last 1 month
  • Followed by GI service for any reason (crohns, ulcerative colitis, constip
  • Developmental delay, patient >1 year behind milestones
  • Current brain tumor
  • Currently being treated for cancer or in remission < 6 months
  • Intussuception
  • Antibiotics in the last 14 days or currently taking antibiotics for any reason
  • Autism
  • Children born premature <33 weeks
  • Cystic Fibrosis
  • Major congenital Heart Disease (any disease where child's baseline oxygen saturations <93%)
  • Short Gut
  • Liver disease
  • History of bowel resection
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198587

Locations
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Children's Hospital Boston
Investigators
Principal Investigator: Michelle L Niescierenko, MD Children's Hospital Boston
Principal Investigator: Richard Bachur, MD Children's Hospital Boston
Principal Investigator: Christopher Duggan, MD, MPH Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Michelle Niescierenko, Clinical Fellow Emergency Medicine, Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT01198587     History of Changes
Other Study ID Numbers: 10-01-0022
Study First Received: September 2, 2010
Last Updated: June 21, 2014
Health Authority: Children's Hospital Boston IRB USA:

Keywords provided by Children's Hospital Boston:
Diarrhea
Gastroenteritis
Zinc Supplementation

Additional relevant MeSH terms:
Diarrhea
Gastroenteritis
Digestive System Diseases
Gastrointestinal Diseases
Signs and Symptoms
Signs and Symptoms, Digestive
Zinc
Zinc Sulfate
Astringents
Dermatologic Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Trace Elements

ClinicalTrials.gov processed this record on November 25, 2014