Immunological and Clinical Responses to Zinc in Children With Diarrhoea

NCT00408356 | Completed Phase 3 DMC

• 1 other identifier: 2004-017
• Study Type: interventional
• Target: 338
• Locations: 1 country
• Sites: 1

Brief Summary

Zinc deficiency has been found to be widespread among children in developing countries.Clinical and field studies have consistently observed an association between zinc deficiency and higher rates of infectious diseases, including skin infections, diarrhea, respiratory infections, malaria, and delayed wound healing. Based upon the impact of zinc deficiency on diarrheal disease alone, it is estimated correction of this deficiency could save 450,000 under-five deaths annually. What is the physiological explanation for this? Zinc has been identified to play critical roles in metallo-enzymes, poly-ribosomes, the cell membrane, and cellular function, leading to the understanding that it also plays a central role in cellular growth and in the function of the immune system. With zinc deficiency epithelial barriers are compromised and multiple components of the immune system malfunction. The obvious conclusion is that zinc deficiency results in diminished immunological competence that in turn leads to an increased risk for infectious diseases and greater severity of illnesses. Whether this is the case requires substantiation. A related, but more pragmatic question is the value added of zinc supplementation in addition to zinc treatment. The scale-up strategy being pursued in Bangladesh is to provide zinc for 10 days as a treatment at the time of a diarrhea episode. This is in accordance with recently revised WHO recommendations for the treatment of childhood diarrhea (WHO, in press). Can we conclude there is no or minimal value added to continuing zinc as a dietary supplement in zinc deficient children following an acute episode? If there is added benefit, can this be explained by improvement in zinc levels and/or immune function? The aims of this study include:1. In children six to twenty-four months of age with an acute episode of diarrhea attributable to enterotoxigenic E. coli (ETEC), to describe the innate and adaptive immune response to zinc and to relate changes in immune function or zinc status to the occurrence of repeat infectious illnesses over a 9 month period of observation. 2a. In children six to twenty-four months of age with an acute episode of diarrhea with enterotoxigenic E. coli (ETEC), and other non-ETEC diarrhea, to determine the value added of zinc supplementation following treatment in terms of the future occurrence of ACD, ARI, and impetigo and 2b. to assess the impact of zinc supplementation on health services utilization and household expenditures for ACD, ARI and impetigo.

Conditions

Diarrhoea

Keywords

Zinc treatment; supplementation; Enterotoxigenic E. coli; diarrhoea

Outcome Measures

Primary Outcomes (2)

• To evaluate innate and adaptive immune response.

• Future occurrence of acute diarrhoea, ARI and impetigo.

Interventions

Zinc DRUG

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children 6-24 months of age with acute childhood diarrheal illness.

You may not qualify if:

• Severe dehydration, suspected cholera or pneumonia, chronic illness, bipedal edema (seriously ill children will be referred to ICDDR,B/Shishu Hospital).
• The child is currently receiving zinc (as a treatment or supplement)
• Wt/length, z-score below -3 (these children will be referred to ICDDR,B/ Shishu Hospital)
• Already participating in another study involving nutritional or therapeutic interventions

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

ICDDR,B. Mirpur Field Site

Dhaka, 1212, Bangladesh

Location

Related Publications (1)

• Sheikh A, Shamsuzzaman S, Ahmad SM, Nasrin D, Nahar S, Alam MM, Al Tarique A, Begum YA, Qadri SS, Chowdhury MI, Saha A, Larson CP, Qadri F. Zinc influences innate immune responses in children with enterotoxigenic Escherichia coli-induced diarrhea. J Nutr. 2010 May;140(5):1049-56. doi: 10.3945/jn.109.111492. Epub 2010 Mar 17.

  PMID: 20237063 DERIVED

MeSH Terms

Conditions

Diarrhea

Interventions

Zinc

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Amit Saha, MBBS

  International Centre for Diarrhoeal Disease Research, Bangladesh

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 5, 2006
• First Posted: December 6, 2006
• Study Start: November 1, 2004
• Primary Completion: August 1, 2006
• Study Completion: November 1, 2006
• Last Updated: February 20, 2009

Record last verified: 2009-02

Locations

BA (1)