Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00513929
Status:
UNKNOWN
Last Update Posted:
2009-01-29
First Post:
2007-08-07
Brief Title:
Zinc as Adjunct to Treatment of Pneumonia
Sponsor:
Corporacion Ecuatoriana de Biotecnologia
Organization:
Corporacion Ecuatoriana de Biotecnologia
Study Overview
Official Title:
Effects of Zinc as an Adjunct to Treatment of Pneumonia in Young Children
Status:
UNKNOWN
Status Verified Date:
2009-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EcuaPAZ
Brief Summary:
The propose of this study is to evaluate if zinc given as an adjunct to standard treatment of severe pneumonia in young children shortens the duration and reduces treatment failure and if these effects are pathogen-dependant
Detailed Description:
Community-acquired pneumonia is a common and potentially serious infection that affects children worldwide The annual incidence of pneumonia in children younger than five years of age is 34 to 40 cases per 1000 in Europe and North America higher than at any other time of life 1 In developing countries pneumonia is not only more common than it is in the developed world 5 to 10 of all children 5 years old but also is more severe and is the largest cause of death in children 1 2 About 20 of deaths in children younger than five years of age are attributable to pneumonia 19 million deaths per year 3 More than 90 of these deaths are in resource-poor countries
Zinc deficiency is widespread in developing countries and is recognized to impair growth and immune function 4 Andean areas are included in the regions with the highest risk of zinc deficiency worldwide 5 In Ecuador 33 of children suffer from zinc deficiency However on the coast of Ecuador where Guayaquil is located the prevalence of zinc deficiency is 37 based on plasma zinc concentration below 70 microgramsdl 6 Stunting which may result from chronic zinc undernutrition is present in 219 of children in Guayaquil 7 In addition in a previous study we reported low dietary zinc intake in children from 12 to 59 months 8 In urban areas of Ecuador breast-feeding is not widely practiced which could put very young children at risk of zinc deficiency 9 Zinc is considered the most abundant intracellular micronutrient that participates in a wide range of cellular processes and plays a central role in the immune response to pathogens 10 We previously demonstrated that zinc supplementation in Ecuadorian children caused an increased response to delayed type hypersensitivity tests to multiple pathogen-derived antigens 8
There is no data available to determine whether the etiologies of pneumonia are dependent on a childs zinc status In general bronchiolitis and upper respiratory tract infections are likely to be viral whereas most cases of severe pneumonia and pneumonia-related deaths are more likely to be bacterial 1 Recently one in vitro study found that zinc mediates antiviral activity on respiratory syncytial virus RSV an etiological agent of pneumonia in children by altering the ability of the cell to support RSV replication 11 If zinc status has an influence on the etiology of pneumonia this suggests that zinc deficiency might be associated with a selective acquired immunodeficiency
Meta-analyses have shown that zinc supplementation is useful for diarrhea and pneumonia prevention in developing countries 12 13 It has been extensively shown that zinc is an important adjunct to diarrhea treatment 13 With regard to pneumonia only three recent studies have reported the use of zinc as an adjunct to antimicrobial treatment for pneumonia in children A clinical study performed in Kolkata India in children with acute lower respiratory infection who were given zinc supplements demonstrated a significant reduction in the duration of fever and very ill status only in boys but not in girls 14 The weaknesses of this trial included the small sample size and the fact that the observed beneficial effect was based on a subgroup analysis Another study performed in Vellore India in a larger group of children younger than 2 years of age demonstrated that zinc as an adjunct to antimicrobial treatment did not have an overall effect on the duration of hospitalization or clinical signs associated with pneumonia 15 In addition Bose et al reported that the use of zinc was associated with an increased duration of clinical signs of pneumonia These different findings could be explained by the dissimilarities between both geographical locations and mean basal plasma zinc concentrations in these studies Kolkata 63 µgdl vs Vellore 72 µgdl Nevertheless a clinical trial performed in Bangladesh reported that the use of zinc as an adjunct to the treatment of severe pneumonia in children reduced the duration of clinical manifestations of the disease including chest indrawing tachypnea hypoxia and length of hospitalization 16 This study had a sample size similar to the trial in Vellore 15 and thus had adequate power In summary there are conflicting results on the effect of zinc given during a severe pneumonia episode in young children Pneumonia etiology is one factor that has been extensively discussed as a possible mechanism to explain the controversial findings of these studies Bose et al suggested that the increased duration of pneumonia signs during zinc supplementation might be due to different etiologies of pneumonia 15 Brooks et al speculated that the observed reductions in pneumonia duration might be explained by zincs role in the acute phase response to pathogens 16 However at present there is no evidence showing that zinc supplementation has an etiology-dependent effect on the clinical evolution of pneumonia In a recent editorial Hambidge also suggested that the controversial findings from these three studies could be due to the basal zinc status of the intervention groups associated pneumonia pathogens and age of the enrolled children 17
Consequently to clarify the role of zinc in relation to pneumonia our study will determine whether or not a low baseline zinc status is associated with the etiology of pneumonia This potential finding may strengthen the scientific evidence that supports mass population zinc supplementation Furthermore this study will also establish if zinc used as treatment adjunct during a severe pneumonia episode results in more rapid clinical recovery from pneumonia Moreover our study intends to evaluate the effect of zinc used as an adjunct to the treatment of pneumonia on the clinical evolution in correlation with the etiology of pneumonia in Ecuadorian children when compared to placebo
Zinc deficiency is widespread in developing countries and is recognized to impair growth and immune function 4 Andean areas are included in the regions with the highest risk of zinc deficiency worldwide 5 In Ecuador 33 of children suffer from zinc deficiency However on the coast of Ecuador where Guayaquil is located the prevalence of zinc deficiency is 37 based on plasma zinc concentration below 70 microgramsdl 6 Stunting which may result from chronic zinc undernutrition is present in 219 of children in Guayaquil 7 In addition in a previous study we reported low dietary zinc intake in children from 12 to 59 months 8 In urban areas of Ecuador breast-feeding is not widely practiced which could put very young children at risk of zinc deficiency 9 Zinc is considered the most abundant intracellular micronutrient that participates in a wide range of cellular processes and plays a central role in the immune response to pathogens 10 We previously demonstrated that zinc supplementation in Ecuadorian children caused an increased response to delayed type hypersensitivity tests to multiple pathogen-derived antigens 8
There is no data available to determine whether the etiologies of pneumonia are dependent on a childs zinc status In general bronchiolitis and upper respiratory tract infections are likely to be viral whereas most cases of severe pneumonia and pneumonia-related deaths are more likely to be bacterial 1 Recently one in vitro study found that zinc mediates antiviral activity on respiratory syncytial virus RSV an etiological agent of pneumonia in children by altering the ability of the cell to support RSV replication 11 If zinc status has an influence on the etiology of pneumonia this suggests that zinc deficiency might be associated with a selective acquired immunodeficiency
Meta-analyses have shown that zinc supplementation is useful for diarrhea and pneumonia prevention in developing countries 12 13 It has been extensively shown that zinc is an important adjunct to diarrhea treatment 13 With regard to pneumonia only three recent studies have reported the use of zinc as an adjunct to antimicrobial treatment for pneumonia in children A clinical study performed in Kolkata India in children with acute lower respiratory infection who were given zinc supplements demonstrated a significant reduction in the duration of fever and very ill status only in boys but not in girls 14 The weaknesses of this trial included the small sample size and the fact that the observed beneficial effect was based on a subgroup analysis Another study performed in Vellore India in a larger group of children younger than 2 years of age demonstrated that zinc as an adjunct to antimicrobial treatment did not have an overall effect on the duration of hospitalization or clinical signs associated with pneumonia 15 In addition Bose et al reported that the use of zinc was associated with an increased duration of clinical signs of pneumonia These different findings could be explained by the dissimilarities between both geographical locations and mean basal plasma zinc concentrations in these studies Kolkata 63 µgdl vs Vellore 72 µgdl Nevertheless a clinical trial performed in Bangladesh reported that the use of zinc as an adjunct to the treatment of severe pneumonia in children reduced the duration of clinical manifestations of the disease including chest indrawing tachypnea hypoxia and length of hospitalization 16 This study had a sample size similar to the trial in Vellore 15 and thus had adequate power In summary there are conflicting results on the effect of zinc given during a severe pneumonia episode in young children Pneumonia etiology is one factor that has been extensively discussed as a possible mechanism to explain the controversial findings of these studies Bose et al suggested that the increased duration of pneumonia signs during zinc supplementation might be due to different etiologies of pneumonia 15 Brooks et al speculated that the observed reductions in pneumonia duration might be explained by zincs role in the acute phase response to pathogens 16 However at present there is no evidence showing that zinc supplementation has an etiology-dependent effect on the clinical evolution of pneumonia In a recent editorial Hambidge also suggested that the controversial findings from these three studies could be due to the basal zinc status of the intervention groups associated pneumonia pathogens and age of the enrolled children 17
Consequently to clarify the role of zinc in relation to pneumonia our study will determine whether or not a low baseline zinc status is associated with the etiology of pneumonia This potential finding may strengthen the scientific evidence that supports mass population zinc supplementation Furthermore this study will also establish if zinc used as treatment adjunct during a severe pneumonia episode results in more rapid clinical recovery from pneumonia Moreover our study intends to evaluate the effect of zinc used as an adjunct to the treatment of pneumonia on the clinical evolution in correlation with the etiology of pneumonia in Ecuadorian children when compared to placebo
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None