Ignite Creation Date:
2024-05-05 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00321126
Status:
COMPLETED
Last Update Posted:
2006-05-03
First Post:
2006-05-02
Brief Title:
Zinc Supplementation in Shigella Patients
Sponsor:
International Centre for Diarrhoeal Disease Research Bangladesh
Organization:
International Centre for Diarrhoeal Disease Research Bangladesh
Study Overview
Official Title:
Effect of Zinc Supplementation on the Immune and Inflammatory Responses of Children to Shigella Flexneri Infection and Correlation With Clinical Severity of Illness and Growth Following recoveryEffect of Zinc Supplementation on the Immune and Inflammatory Responses of Children to Shigella Flexneri Infection and Correlation With Clinical Severity of Illness and Growth Following Recovery
Status:
COMPLETED
Status Verified Date:
2006-05
Last Known Status:
None
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:
None
Brief Summary:
Shigellosis is a major cause of morbidity and mortality in young children in Bangladesh and other developing countries Further the increasing emergence of resistance to a wide range of antibiotics is of great concern Another major public health problem in Bangladesh is malnutrition which is closely linked with shigellosis and with a high mortality In Shigellosis a heavy nutritional burden is placed on children and vital micronutrients such as vitamin A is lost in the urine We recently found that the immune response in S Flexneri infection was lower in children who were severely malnourished weight-for-age65 as a percentage of the National Centre for Health Statistics median when compared to children with weight-for-age from 65-75 T cell responses were primarily affected with lowered CD4CD8 ratios lowered proliferative responses to T cell mitogens Conconavalin A ConA and phytohaemagglutinin PHA However proliferation of pheripheral blood mononuclear cells PBMs was lowered only in the presence of autologous plasma suggesting that a factors in plasma probably nutritional rather than a defect in cells themselves was responsible In children with S dysenteriae 1 infection proliferative responses to PHA were similarly lowered in the presence of autologous plasma but inhibition correlated to lowered transferring levels in plasma and not to the weight-for-age of the children Also severely malnourished children with either S flexneri or S dysenteriae 1 infection were more severely ill These findingings show that immunity in malnourishrd children with shigella infection is impaired which may lead to more severe illness As zinc has profound effects on immunity as well as clinical outcome in diarrhoeal diseases it is possible that zinc deficiency may be a factor in reducing immunity and increasing severity of acute illness in malnourished children with shigellosis In this study we will investigate the effect of zinc supplementation in a double blind placebo controlled trial on inflammatory responses outcome of acute illness and growth following recovery from acute illness with S flexneri infection
Detailed Description:
Study design The study was a double blind randomised clinical trial using zinc and placebo using multivitamin baseStudy subjects Fifty six children of both sex aged between 12-59 months were studied in the study ward who attended the Dhaka Hospital of International Centre for Diarrhoeal Disease Research Bangladesh with shigellosis The patients were initially screened for the study Stool samples were examined microscopically and stool was cultured for enteric bacterial pathogens Children whose stool cultures were positive for shigella species were included in the study Selection of the patients were based on the following criteria age between 12-59 months moderate malnutrition 61-75 Weight Age - NCHS Median duration of diarrhoea of 5 days and culture confirmed shigella spp in stool on enrolment Measurements of weight and length height were performed by using the WHO Manual28 The exclusion criteria were as follows measles infection in the past six months presence of obvious systemic illnesses such as pneumonia meningitis septicaemia leukemoid reaction haemolytic uremic syndrome etc zinc supplementation severe malnutrition residence in a location requiring a journey of 2 hour from the Dhaka Hospital of the ICDDRB and refusal to give consent Signed informed consent was obtained from the guardian of each paediatric patients before enrolment according to the guidelines of the ethical review committee of the ICDDRB The study was conducted between January 1999 -December 2002Study Groups There were two study groups one received zinc acetate with multivitamin syrup and antibiotic ie pivmecillinum and the other with placebo and pivmecillinum Composition of syrup For both groups the base syrup or multivitamin syrup was of the same composition In addition to this zinc acetate 20 mg elemental Zn 5 ml was mixed in the multivitamin syrup for the zinc supplemented group to receive 20 mg elemental zinc per dayComposition of base multivitamin syrup Every 5 ml of the multivitamin syrup contained the following vitamin A 3000IU vitamin D 600 IU thiamin 12 mg riboflavin 20 mg nicotinamide 60 mg and calcium pantothanate 6 mgDose of zinc Subjects of zinc group received 20 mg elemental zinc as acetate per day in a twice-daily dose for a period of 2 weeks Methods A block randomization procedure was performed by using a random table to assign a equal number of patients to the zinc supplemented and placebo group Twenty eight in each group were allocated to zinc or placebo using block randomization Double blinding was done by having identical coloured bottles of syrup labeled with serial numbers which were allocated to the children of the 2 groups chronologically The zinc syrup containing zinc and the multivitamin was masked for taste and flavor and was indistinguishable in consistency appearance and taste from the control syrup containing the multivitamin only The micronutrient supplements were prepared by Acme Laboratories Dhaka Bangladesh The experimental group received the zinc syrup containing the multivitamin the vitamins were given at twice the recommended dietary allowance in 2 divided doses daily for 2 weeks starting from the day of admission The comparison group received the same multivitamin syrup alone All the subjects received pivmecillinum in a dose of 60 mgkgday in 4 divided doses for 5 days In both groups of patients diarrhea subsided within 3-5 days During hospitalization all the study children received a standard hospital diet of 100-125 kcal and 3-5 g protein per kg body weight daily in mixed food When discharged at day-7 their mothers were given the bottles of syrup and were instructed to feed the child with the supplement daily at home for rest 7 days On the 14th day a health assistant visited the household measured the amount of syrup taken and also enquired the mothers about any problems encountered during feeding of syrups Children were followed up fortnightly for up to 6 months after the onset of diarrhoea to assess morbidity and growth The following was investigated during the study period -Clinical evaluation duration of illness presence of blood in stool tenesmus and weight changesAssessment of growth and growth velocity Measurements included weight height triceps skinfold thickness TSF using standard technique WHO28 These were done before supplementation and at discharge After supplementation children were measured every two weeks at home Weights were obtained to the nearest 10 g using an electronic digital scale Secca model 770 Sweden standarised with 5 and 10 kg standard weights in everyday morning and evening Recubent length was measured in children less than two years of age using a slide board infantometer Harpenden St Albans England In older children standing height was determined with a Stadiometer Mean of two consecutive height measurements to the nearest 05 cm was recorded as the observe value Measurements were compared to Median NCHS Standard Health workers were extensively trained in anthropometric measurements until minimum intra-individual and inter individual variation was attainted Statistical AnalysisThe data were checked daily at recording by the investigators cleaned and then entered in microcomputer using SPSSPC Windows 100 Data analysis was performed using SPSSPC Windows 100 and EPI Info Nutritionversion 322 The consistency check was done using logical programs Student and paired t-tests were used when data were normally distributed and non- parametric Mann-Whitney U tests were used when the distribution were skewed Time sequence of proportions of recovery was compared between two groups using Kaplan Meier survival analysis Proportions were compared using chi-squared test Repeated measure analyses of variance were also undertaken to evaluate the changes in weight gain and length gain over the follow-up periods Statistical significance was accepted at 5 percent level
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