View clinical trials related to Severe Acute Malnutrition.
Filter by:Ready-to-use therapeutic food (RUTF) is the standard of care for the treatment of SAM. UNICEF requires that there be no oil separation in these products necessitating the use of emulsifiers. The effect of emulsifiers on gut health and integrity in children receiving an exclusive diet of RUTF is unknown. The PIs have recently completed a randomized, triple-blind, controlled, clinical equivalency trial in Sierra Leone comparing the alternative oat RUTF (oat-RUTF) to standard RUTF on recovery rates in children with SAM. This study demonstrated higher rates of recovery among children receiving the oat-RUTF. The investigators hypothesize that this benefit may be due to the lack of emulsifier in the oat-RUTF resulting in improved intestinal health.This research project is a double-blind, randomized, controlled clinical effectiveness trial comparing a novel RUTF containing oats and no emulsifier and standard RUTF on recovery from severe acute malnutrition (SAM) and effects on intestinal health. The trial will be conducted in up to 40 PHUs in Western Rural and Pujehun Districts where supplementary feeding programs (SFP) are not currently available.
Acute malnutrition affects 51 million children under the age of 5 worldwide. Malnutrition contributes to nearly half of all child deaths each year, with the forms characterized by wasting or oedema (acute malnutrition) associated with the highest risk of death. Although acute malnutrition is a continuum condition, it is arbitrarily divided into severe and moderate acute malnutrition (SAM, MAM) which are managed separately, with programs overseen by different UN agencies, and using different protocols and products. Such separation complicates delivery of care, contributes to high default and low coverage, and creates confusion among caregivers. Often treatment is only available for SAM children resulting in lives lost and costly hospitalisation that could be averted if nutritional support were available earlier in the wasting process. If we are to reduce the health and mortality burden from malnutrition, the effectiveness and cost-effectiveness of current protocols need dramatic improvements. The dosage of Ready to Use Therapeutic Food (RUTF) for SAM (130-200 kcal/kg/d) has not changed since introduction of out-patient protocols in the mid-2000s. Children classified as SAM in these protocols are determined by three independent criteria: the presence of nutritional oedema or MUAC < 115 mm or weight-height Z score <-3. The RUTF dosage in these protocols is paradoxical in that the absolute amount of RUTF prescribed in the initial phases of treatment is often less than that given as the child nears recovery, because the number of packets in the weekly ration is determined by weight. However, rate of weight gain (g/kg/day) is highest in the first two weeks of treatment, and then plateaus - suggesting no benefit of increased RUTF amounts in the later phases of treatment. Progressive reduction seems to be a more rational use of RUTF. The Optimizing treatment for acute MAlnutrition (OptiMA) strategy consists in simplifying management of acute malnutrition through the use of a single anthropometric admission criterion (mid upper arm circumference [MUAC] < 125 mm or nutritional oedema) - one that best captures children's anthropometry related mortality risk- and by optimizing the use of RUTF by adapting doses to the nutritional recovery of the child. RUTF doses begin at 170 kcal/kg/d for the most severely wasted (MUAC < 115 mm or oedema) and reduce to 75 kcal/kg/d as oedema resolves and MUAC increases > 120 mm. The investigators hypothesize that this strategy could double the number of children in care compared to current SAM programs without substantially increasing the amount of RUTF or staffing required while maintaining a recovery rate in line with current programs. OptiMA may also improve coverage and reduce the need for hospitalization through early identification of malnourished children. The investigators propose to conduct a community-based non-inferiority clinical trial with individual randomization comparing the OptiMA strategy to the Democratic Republic of Congo standard nutritional protocol for SAM. Study children will be randomly assigned to the intervention arm or control arm - with children at MUAC < 125 mm or oedema eligible for RUTF in the intervention arm and those meeting current WHO SAM definition eligible in the control group. All participants will be followed for 9 months post-randomization to assess non-inferiority as defined by a composite of three endpoints : alive, acceptable nutritional status (MUAC ≥ 125 mm and WHZ >-3, no oedema) and no relapse to acute malnutrition for those who were treated with RUTF. The main secondary outcome will assess the non-inferiority of OptiMA RUTF dosing (170 kcal/kg/d) in children meeting current WHO SAM criteria compared to children with the same criteria in the control arm who will receive 130-200 kcal/kg/d.
The TAME study will evaluate four new approaches which will be compared against the standard care currently in use in the treatment of malnutrition enteropathy in children with severe acute malnutrition. A high pathogen burden causes damage to the intestinal mucosa which exacerbates nutritional impairment and leads to further susceptibility to infection and impaired epithelial regeneration. Enteropathy is characterised by multiple epithelial breaches, microbial translocation from gut lumen to systemic circulation and systemic inflammation.The trial will evaluate the potential impact of four interventions (colostrum, N-acetyl glucosamine, teduglutide, and budesonide) given for 14 days, which aim at mucosal restoration. The trial will determine if repairing damage to the small intestinal mucosa leads to the reduction of systemic inflammation and thus lessening the nutritional impairment, and so if this contributes to the reduction of mortality in children. In Zambia only, endoscopic biopsies and confocal laser endomicroscopy will be used to evaluate response and confirm safety at a mucosal level. Identifying an agent or agents which contribute most to mucosal healing will then ultimately lead to further large phase 3 trial in which the agent(s) will be further evaluated. The trial also anticipates to gain a more in depth understanding of pathophysiology and may identify where current management strategies of treating malnutrition enteropathy in children are failing.
Malnutrition is an ever-present problem worldwide. It is estimated that over 18 million children under the age of 5 are affected by the most extreme form of undernutrition, severe acute malnutrition (SAM). In spite of having standardized management protocols, in many hospitals, inpatient mortality reaches up to 30%. Infectious morbidity is common among survivors. Diarrhea, severe intestinal inflammation, low concentrations of fecal short-chain fatty acids (SCFAs), and severe systemic inflammation are significantly associated with mortality in SAM. Investigators of this study have earlier shown that the gut microbiota in children with SAM is immature and is causally related to SAM. Human milk contains between 10 and 20 g/liter of oligosaccharides (human milk oligosaccharides-HMOs) which is the third most abundant solid component after lactose and lipids. HMOs are resistant to gastrointestinal digestion in host infants, and thus the greater part of HMOs reached the colon and may act as prebiotics to shape a healthy gut ecosystem by stimulating the growth of useful microorganisms by acting as receptor analogs to inhibit the binding of various pathogens and toxins to epithelial cells. Probiotics are live organisms beneficial for a healthy life. The human digestive tract possesses a diverse microbial community throughout its extent, which supports their hosts generally for healthy living. Bifidobacterium spp. is dominant microbiota in infants who are exclusively breastfed and these infants are less likely to suffer from diarrhea. According to recent studies among the most common probiotics genera Lactobacillus and Bifidobacterium, the latter is more abundant in the gut. To carry out their functional activities, Bifidobacteria must be able to survive the gastrointestinal tract transit and persist, at least transiently, in the host. The population of Bifidobacteria in the gut community drastically decreases after weaning. Certain Bifidobacteria possess the metabolic capabilities to break down the HMOs. Consequently, it is observed that HMOs support the growth of select Bifidobacteria in the gut of the infant. Research done at icddr,b and Washington University indicates that gut microbes are related to undernutrition and that children with SAM have gut dysbiosis that mediates some of the pathologies of their condition. The standard of care in these children should be reinforced by an intervention that corrects the gut dysbiosis, improves weight gain during nutritional rehabilitation, and reduces infectious morbidity. Investigators do not have any published data on the microbiome response to probiotic supplementation (with and without prebiotics) in malnourished infants or preserving the microbiome with probiotics in non-malnourished children. A short-term pilot study should be conducted to evaluate the microbiome response to probiotic supplementation (with and without prebiotics) in malnourished populations to justify a larger study of clinical outcomes. Additionally, non-malnourished infants who are hospitalized for infectious conditions face challenges related to gut dysbiosis caused by antibiotic usage. Here the investigators will evaluate the ability of a probiotic intervention to rescue the microbiome of primarily breastfed non-malnourished infants. Intervention: Bifidobacterium longum subspecies infantis (EVC001) with and without prebiotic supplementation for 28 days. Objectives: To evaluate the microbiome response to probiotic supplementation (with and without prebiotics) in infants under 6 months with severe acute malnutrition and to compare the microbiome response with healthy infants with a probiotic. Methods: Single-blind RCT, stratified randomization will be based on infant age at the time of transfer to the Nutritional Rehabilitation Unit (NRU). 3 treatment arms for infants with SAM 1. Placebo (Lactose) 2. Bifidobacterium infantis alone (Bif) 3. Bifidobacterium infantis + prebiotic Lacto-N-neotetraose [LNnT] (Bif+prebiotic) Age at enrollment 1. 2-3.9 months of age 2. 4-5.9 months of age 1 open-label treatment arm for 18 non-malnourished primarily breastfed infants: Bifidobacterium infantis alone (Bif) Population: 1. Group 1 (SAM): Infants between 2 and <6 months old with SAM as defined by weight-for-length Z score < -3 either sex, caregiver willing to provide consent for enrolment of the infant, caregiver willing to stay in the NRU for about 15 days, residence within 15 km from icddr,b 2. Group 2 (non-malnourished): Non-malnourished infants (WLZ ≥ -1) <6 months old who are hospitalized for treatment with antibiotics for the infection, infants receiving at least 50% of nutritional intake from breast milk at the time of hospitalization, either sex, residence within 15 km from icddr,b Primary Outcome measures/variables: Bifidobacterium infantis colonization measured by qPCR during and after supplementation (with and without prebiotics)
Except for children with HIV, all recommendations for treatment of childhood malnutrition are for children < 5 years of age. The overall goal of this randomized controlled nutrition feasibility trial is to identify whether families of children with sickle cell disease (SCD) 5 years and older agree to participate over a 12-week period. The investigators will also establish a safety protocol for monitoring potential complications associated with treating severe malnutrition in children 5 years and older with and without SCD, in a low-resource setting.
This pilot study is a randomized controlled trial designed to test the effect of the administration of adjunctive azithromycin in conjunction with standard outpatient treatment for uncomplicated severe acute malnutrition (SAM) in children aged 6-59 months. Children presenting to nutritional programs in Burkina Faso who meet eligibility criteria will be randomized to a single dose of oral azithromycin or a 7-day course of amoxicillin (standard of care) upon admission into the program. All enrolled children will receive ready-to-use therapeutic foods (RUTF). Enrolled children will be followed at each weekly clinic follow-up visit up to 8 weeks following admission. Data on anthropometric indicators, vital status, and adverse events will be collected during follow-up. Nutritional recovery over the 8-week study period will be compared by arm.
In this clinical non-inferiority trial, two foods will be compared for the treatment of SAM, testing the hypothesis that the difference in recovery rates and growth between the two test groups will be no greater than 5 percent.
INTRODUCTION In 2014, 50 million children under 5 suffered from acute malnutrition, of which 16 million suffered from SAM, most of them living in sub-Saharan Africa and Southeast Asia. SAM children have higher risk of mortality (relative risk between 5 and 20). It is an underlying factor in over 50% of the 10 - 11 million preventable deaths per year among children under five. At present, 65 countries have implemented WHO recommendations for SAM treatment (both in-patient for complicated cases and outpatient for uncomplicated cases) but these programs have very low coverage, reaching only around 10 - 15 % of SAM children. In 2009 the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) issued a joint statement in an effort to harmonize the application of anthropometric criteria for SAM diagnosis and monitoring in child aged 6 - 59 months; the statement presents recommended cut-offs, and summarizes the rational for the adoption, of the following two anthropometric criteria: 1. Weight-for-Height Z-Score (WHZ): "WHO and UNICEF recommend the use of a cut-off for weight-for-height of below -3 standard deviations (SD) of the WHO standards to identify infants and children as having SAM." Additionally, analysis of existing data show that children with a WHZ < -3 have a highly elevated risk of death. 2. Mid-Upper Arm Circumference (MUAC): "WHO standards for the MUAC-for-age show that in a well-nourished population there are very few children aged 6 - 59 months with a MUAC less than 115 mm. Children with a MUAC less than 115 mm have a highly elevated risk of death compared to those who are above. Thus it is recommended to [use] the cut-off point [of] 115 mm to define SAM with MUAC." GENERAL OBJECTIVE To generate new evidence on pathophysiological process, nutritional needs and risks associated with different types of anthropometric deficits in children under 5, in order to optimize the diagnosis and treatment of SAM. SPECIFIC OBJECTIVES - To compare nutritional status, metabolism, pathophysiological process and risks in different types of SAM anthropometric diagnosis, with or without concomitant stunting (growth retardation). - To analyze the extent to which current SAM treatment is promoting recovery and healthy growth in different categories of children. - To evaluate the relevance of current discharge criteria used in nutrition programs and their association with metabolic recovery, in different age groups and among those who are stunted. - To test novel rapid tests of emerging biomarkers predicting long-term outcomes and mortality risk in the field. METHODOLOGY A wide range of supplementary information related to nutritional status, body composition, metabolic and immune status, including emerging biomarkers of metabolic deprivation and vulnerability, will be collected besides anthropometry during prospective observational studies. They will be collected with minimum level of invasiveness, compatible with field work requirements in the humanitarian context. Phase 1: Cross-sectional surveys. Phase 2: Prospective cohort studies involving SAM children between 6 months and 5 years old. Children admitted as SAM at the nutrition centers will be enrolled into the cohort. The follow up duration will be at least three months. EXPECTED OUTCOMES - Confirmation of current hypotheses related to: 1. possible misdiagnosis of SAM made by MUAC or WHZ criteria, 2. varying degree of severity and need for admission to treatment of the different types of diagnosis, 3. underlying heterogeneity of the pathophysiology. - Generation of new algorithms for the assessment and classification of malnourished children, based on the combined use of emerging biomarkers and anthropometric measures, or on the modification of anthropometric criteria. - Generation of new treatment paradigms based on the predictive value of biomarkers in combination with traditional anthropometric measures. This will enable us to assess the power of current treatment regimens to promote long-term weight gain and growth and will allow us to tailor treatment to the physiological needs of the child.
To evaluate, in routine operational settings of treatment of uncomplicated Severe Acute Malnutrition (SAM) in children aged 6-59 months, the risk of nutritional recovery and hospitalization with non-routine use of amoxicillin compared to the risk achieved with systematic use of antibiotics.
While the standardization of treatment protocols for Severe Acute Malnutrition (SAM) has helped to reduce historically high mortality, mortality in inpatient settings remains substantial, likely due to the severity of complications associated with late presentation and health-care associated infection (HCAI). The purpose of this study is to serve as an important stand-alone description to inform the understanding of the magnitude of the problem and help guide implementation of measures to reduce the risk of nosocomial infection and multi-drug resistance.