Ignite Creation Date:
2024-05-06 @ 4:46 PM
Last Modification Date:
2024-10-26 @ 2:15 PM
Study NCT ID:
NCT05083637
Status:
COMPLETED
Last Update Posted:
2024-03-07
First Post:
2021-10-05
Brief Title:
L-Carnitine Supplementation Rate of Weight Gain and EED in Children With SAM
Sponsor:
International Centre for Diarrhoeal Disease Research Bangladesh
Organization:
International Centre for Diarrhoeal Disease Research Bangladesh
Study Overview
Official Title:
Role of L-Carnitine Supplementation on Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction EED in Children With Severe Acute Malnutrition
Status:
COMPLETED
Status Verified Date:
2023-01
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:
Background
Burden
Globally an estimated 143 million under-5 children are severely malnourished Two-thirds of them live in Asian countries including Bangladesh Acute malnutrition is an underlying cause of nearly half of global deaths in under-5 children despite standardized rehabilitation protocols It is also associated with high relapse rates following discharge
Knowledge Gap
Malnourished children suffer from deficiencies of several essential nutrients Studies showed that malnourished children had lower serum carnitine levels and demonstrated its role in the rate of weight gain in children with severe acute malnutrition SAM The consequences of nutritional impairment can be perilous if carnitine deficiency is coupled with Environmental Enteric Dysfunction EED Recent evidence confirms that EED is characterized by secondary carnitine deficiency in children Carnitine deficiency leading to EED may cause childhood growth faltering and impaired cognitive development However evidence on carnitine status and its consequences in relation to EED in diarrheal children with SAM is very limited in Bangladesh
Relevance
Such lack of information regarding the role of L-carnitine in improving the rate of weight gain in malnourished children susceptible to EED is an obstacle in limiting the relapse and adverse consequences of SAM in diarrheal children living in resource-limited countries
Hypothesis L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED
Objective
1 To investigate the role of L-carnitine supplementation on the rate of weight gain among the children with SAM
2 To investigate the role of L-carnitine supplementation on the duration of the hospital stays
3 To examine the role of L-carnitine supplementation on EED biomarkers for instance myeloperoxidase MPO neopterin NEO alpha-1 anti-trypsin A1AT kynurenine tryptophan KT ratio and citrulline in children with SAM
Methods This study will be a double-blinded placebo-controlled randomized clinical trial
Burden
Globally an estimated 143 million under-5 children are severely malnourished Two-thirds of them live in Asian countries including Bangladesh Acute malnutrition is an underlying cause of nearly half of global deaths in under-5 children despite standardized rehabilitation protocols It is also associated with high relapse rates following discharge
Knowledge Gap
Malnourished children suffer from deficiencies of several essential nutrients Studies showed that malnourished children had lower serum carnitine levels and demonstrated its role in the rate of weight gain in children with severe acute malnutrition SAM The consequences of nutritional impairment can be perilous if carnitine deficiency is coupled with Environmental Enteric Dysfunction EED Recent evidence confirms that EED is characterized by secondary carnitine deficiency in children Carnitine deficiency leading to EED may cause childhood growth faltering and impaired cognitive development However evidence on carnitine status and its consequences in relation to EED in diarrheal children with SAM is very limited in Bangladesh
Relevance
Such lack of information regarding the role of L-carnitine in improving the rate of weight gain in malnourished children susceptible to EED is an obstacle in limiting the relapse and adverse consequences of SAM in diarrheal children living in resource-limited countries
Hypothesis L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED
Objective
1 To investigate the role of L-carnitine supplementation on the rate of weight gain among the children with SAM
2 To investigate the role of L-carnitine supplementation on the duration of the hospital stays
3 To examine the role of L-carnitine supplementation on EED biomarkers for instance myeloperoxidase MPO neopterin NEO alpha-1 anti-trypsin A1AT kynurenine tryptophan KT ratio and citrulline in children with SAM
Methods This study will be a double-blinded placebo-controlled randomized clinical trial
Detailed Description:
Study Design
Study Site
This study will be done in the Dhaka Hospital at icddrb
Study population
In this study the investigator will enroll diarrheal children with SAM aged 9-24 months of both genders attending longer stay units LSU
Study duration 12 months
Screening Consenting and Baseline Data Collection
The research staff Field Research Assistant will screen all the participants within the defined age groups according to the eligibility criteria Detailed inclusionexclusion criteria are provided separately below Then research staff will explain the study in detail answer any questions from the parents and invite the parents to enroll the child in the study If the parents are interested in volunteering in the study the designated staff will proceed to consent consisting of a thorough review of the written consent form in a manner appropriate for the childs parents literacy level Prior to signing the consent form parents will have an opportunity to ask any questions about the study participants fulfilling the eligibility criteria will be brought to the study physician for clinical assessment If the parents are not sufficiently literate to read andor sign the consent form consenting and fingerprint signature will be obtained in the presence of a witness who is not associated with the study The childs parents will be provided with a copy of the signed consent form Upon signing a written informed consent the participant will be enrolled by the study physician
Randomization
Participants will be assigned to the intervention or the control arm using permuted block randomization method with concealment to ensure that the allocation is not made before the participant has given their consent and joined the study A random allocation sequence will be generated using a computerized random allocation system for permuted block randomization to ensure comparable allocation numbers at certain equally spaced points in the sequence of patient assignments A parallel type of randomization will be used Reasonably large blocks with variable block sizes will be constructed to reduce the predictability Random assignment will be prepared in advance by an independent researcher from icddrb who has no involvement with the trial
Anthropometric measurements
All the measurements will be taken at enrollment and each day when the participants will receive interventionplacebo End-line anthropometry data will be collected on the 15th day of supplementation In addition we will measure anthropometry on the 180th day after the completion of supplementation to observe the long-term effect of the intervention on the rate of weight gain Trained staff will take all the measures as per the standard operating procedures SOPs and keep records in standard CRFs The Seca weighing scale will be used for weight measurement in kg and the Seca length board will be used for length measurement in cm And mid-upper arm circumference MUAC will be measured in cm using a non-stretch tape
Intervention
The intervention will be given to the child along with the standard of treatment at the nutritional rehabilitation unit NRU Detailed information about the investigational product is provided separately below Children will be monitored daily by trained physicians for any side effectsadverse events such as nausea vomiting diarrhea rash urticaria or any significant changes in clinical status If any adverse events are observed children will be treated using appropriate management practices at Dhaka Hospital
Biological sample collection
The investigators will collect blood stool and urine from the participants at enrolment and at the end of the nutrition intervention Overall 5 ml of whole venous blood will be collected aseptically from each of the participants as per the SOPs The blood biomarkers that will be tested in this study are L-carnitine Citrulline KT Ratio C-reactive protein CRP and Alpha-1-acid glycoprotein AGP CRP is an acute-phase protein and can be detected during infection Increased level of AGP in serum indicates systemic tissue injury inflammation and infection Both Citrulline and KT ratios indicate EED in children The stool will be collected to investigate the concentrations of MPO NEO and A1AT in the fecal samples The investigators will measure L-carnitine levels in the urine samples of each participant All the assays will be done at icddrb
Laboratory Investigation
The investigators will measure L-carnitine levels in plasma and urine and EED biomarkers in every enrolled patient Pre and post-test will be done The pre-test will be on the first day of enrolment and the post-test will be on the 15th day after the completion of supplementation
Sample Size Calculation
The sample size is estimated considering the primary outcome variable For the primary objective the investigators have considered an intervention study in Turkey The study discovered that the mean difference between the rate of weight gain in malnourished children after L-carnitine supplementation was 24 The weight was measured in kg with a standard deviation of 43 Setting the level of confidence at 95 Z1-α 1645 and the study power at 80 the estimated sample size is 49 participants in each group with a 10 attrition rate So the total sample size for this study will be 98
Data Analysis Plan
Data will be entered into the pre-tested case record forms CRFs using Statistical Package for the Social Sciences SPSS 200 version and finally cleaned with a repeated check Data will be presented using frequency with percentages for categorical variables Mean with standard deviation will be used for symmetrical continuous variables Median with interquartile range will be used for asymmetrical numeric variables To know the outcome of the intervention in our study children bivariate crude analyses of the association will be done that will involve Chi-square or Fishers exact test for comparing differences in proportion and t-tests for numeric variables between the groups Nonparametric continuous data will be analyzed by Mann-Whitney U-test Results from all children will be included in the analysis of the study on an intention-to-treat basis Data from children withdrawn because of failure to respond or voluntary dropouts will be included in the analysis up to the time of withdrawal A supplementary analysis excluding the children withdrawn may also be done A probability of less than 005 will be considered statistically significant
Study Site
This study will be done in the Dhaka Hospital at icddrb
Study population
In this study the investigator will enroll diarrheal children with SAM aged 9-24 months of both genders attending longer stay units LSU
Study duration 12 months
Screening Consenting and Baseline Data Collection
The research staff Field Research Assistant will screen all the participants within the defined age groups according to the eligibility criteria Detailed inclusionexclusion criteria are provided separately below Then research staff will explain the study in detail answer any questions from the parents and invite the parents to enroll the child in the study If the parents are interested in volunteering in the study the designated staff will proceed to consent consisting of a thorough review of the written consent form in a manner appropriate for the childs parents literacy level Prior to signing the consent form parents will have an opportunity to ask any questions about the study participants fulfilling the eligibility criteria will be brought to the study physician for clinical assessment If the parents are not sufficiently literate to read andor sign the consent form consenting and fingerprint signature will be obtained in the presence of a witness who is not associated with the study The childs parents will be provided with a copy of the signed consent form Upon signing a written informed consent the participant will be enrolled by the study physician
Randomization
Participants will be assigned to the intervention or the control arm using permuted block randomization method with concealment to ensure that the allocation is not made before the participant has given their consent and joined the study A random allocation sequence will be generated using a computerized random allocation system for permuted block randomization to ensure comparable allocation numbers at certain equally spaced points in the sequence of patient assignments A parallel type of randomization will be used Reasonably large blocks with variable block sizes will be constructed to reduce the predictability Random assignment will be prepared in advance by an independent researcher from icddrb who has no involvement with the trial
Anthropometric measurements
All the measurements will be taken at enrollment and each day when the participants will receive interventionplacebo End-line anthropometry data will be collected on the 15th day of supplementation In addition we will measure anthropometry on the 180th day after the completion of supplementation to observe the long-term effect of the intervention on the rate of weight gain Trained staff will take all the measures as per the standard operating procedures SOPs and keep records in standard CRFs The Seca weighing scale will be used for weight measurement in kg and the Seca length board will be used for length measurement in cm And mid-upper arm circumference MUAC will be measured in cm using a non-stretch tape
Intervention
The intervention will be given to the child along with the standard of treatment at the nutritional rehabilitation unit NRU Detailed information about the investigational product is provided separately below Children will be monitored daily by trained physicians for any side effectsadverse events such as nausea vomiting diarrhea rash urticaria or any significant changes in clinical status If any adverse events are observed children will be treated using appropriate management practices at Dhaka Hospital
Biological sample collection
The investigators will collect blood stool and urine from the participants at enrolment and at the end of the nutrition intervention Overall 5 ml of whole venous blood will be collected aseptically from each of the participants as per the SOPs The blood biomarkers that will be tested in this study are L-carnitine Citrulline KT Ratio C-reactive protein CRP and Alpha-1-acid glycoprotein AGP CRP is an acute-phase protein and can be detected during infection Increased level of AGP in serum indicates systemic tissue injury inflammation and infection Both Citrulline and KT ratios indicate EED in children The stool will be collected to investigate the concentrations of MPO NEO and A1AT in the fecal samples The investigators will measure L-carnitine levels in the urine samples of each participant All the assays will be done at icddrb
Laboratory Investigation
The investigators will measure L-carnitine levels in plasma and urine and EED biomarkers in every enrolled patient Pre and post-test will be done The pre-test will be on the first day of enrolment and the post-test will be on the 15th day after the completion of supplementation
Sample Size Calculation
The sample size is estimated considering the primary outcome variable For the primary objective the investigators have considered an intervention study in Turkey The study discovered that the mean difference between the rate of weight gain in malnourished children after L-carnitine supplementation was 24 The weight was measured in kg with a standard deviation of 43 Setting the level of confidence at 95 Z1-α 1645 and the study power at 80 the estimated sample size is 49 participants in each group with a 10 attrition rate So the total sample size for this study will be 98
Data Analysis Plan
Data will be entered into the pre-tested case record forms CRFs using Statistical Package for the Social Sciences SPSS 200 version and finally cleaned with a repeated check Data will be presented using frequency with percentages for categorical variables Mean with standard deviation will be used for symmetrical continuous variables Median with interquartile range will be used for asymmetrical numeric variables To know the outcome of the intervention in our study children bivariate crude analyses of the association will be done that will involve Chi-square or Fishers exact test for comparing differences in proportion and t-tests for numeric variables between the groups Nonparametric continuous data will be analyzed by Mann-Whitney U-test Results from all children will be included in the analysis of the study on an intention-to-treat basis Data from children withdrawn because of failure to respond or voluntary dropouts will be included in the analysis up to the time of withdrawal A supplementary analysis excluding the children withdrawn may also be done A probability of less than 005 will be considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None