Active clinical trials for "Severe Acute Malnutrition"

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 Placebo (Lactose) Bifidobacterium infantis alone (Bif) Bifidobacterium infantis + prebiotic Lacto-N-neotetraose [LNnT] (Bif+prebiotic) Age at enrollment 2-3.9 months of age 4-5.9 months of age 1 open-label treatment arm for 18 non-malnourished primarily breastfed infants: Bifidobacterium infantis alone (Bif) Population: 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 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)

The goal of this clinical trail study is to measure neurophysiologic parameters to assess the effect of malnutrition on the peripheral nervous system and their response to treatment in three categories (SAM, severe wasting, and severe stunting) of childhood malnutrition. 83 under-5 children from three categories of undernourished groups- severe stunting (n=30), Severe acute malnourished (n=22), wasting (n=31), and 45 age-matched healthy children from urban/peri-urban areas were enrolled. SAm were provided with appropriate nutritional therapy/treatment that include supplementation of a high-calorie diet; i.e., F-100 milk and khichuri-halwa for nutritional rehabilitation. Egg milk and micronutrient supplementation were for recovery from severe stunting. Wasted children were treated with suitable local nutritional management (NM), such as infant and young child feeding practices (IYCF), providing MNP and nutrition education. Wasted children with medical complications were treated with specialized therapeutic milk (F-75) and those without medical complications were treated with a suitable local Nutritional Management (NM) & routine medicines to treat simple medical conditions at community nutrition center (CNC) with weekly follow up. At day 60 of intervention, children were again brought to icddr,b for a nerve conduction test.

Globally, in 2011, 52 million children under 5 years old suffered from acute malnutrition, and a further 165 million children showed evidence of chronic undernutrition or stunting. It was also estimated that 3.1 million children died in 2011 of malnutrition related causes. The survivors, due to deprivation of critical nutrients in the most important period of development and growth, are left with permanent damage, including an increased risk of cardio-metabolic disease, poorer educational achievement and diminished earning potential. In Jamaica in 2012, 2.5% of children were moderately or severely underweight (more than two standard deviations below weight-for-age by international reference populations), falling from as high as 8.9% in 1993. Though there have been modest reductions in the incidence of acute malnutrition in Jamaica over the past 20 years, the risk remains high in poor families and among children who are being weaned. Hence, the problem is an ongoing one and we have a significant pool of survivors of childhood malnutrition who have now reached adulthood and face the consequences of early nutrient deprivation. The brain is particularly vulnerable to the effects of malnutrition and studies have demonstrated both structural (brain atrophy) and functional (cognitive impairment and poor academic achievement) changes. This evidence, however, has been mainly in later childhood and adolescence. In addition, there is local data that suggests that cardio-metabolic risk factors are increased in these adult survivors, which are well-described precursors of cerebrovascular disease and cognitive impairment. Therefore, in adulthood there may be accelerated cognitive decline due to a poor cardio-metabolic profile superimposed on pre-existing brain injury. We hypothesise that there are differences in cognitive function (poorer memory and executive function)and emotional responses in adult survivors of childhood malnutrition compared to those not exposed to early childhood malnutrition. There is evidence suggesting that aerobic exercise and omega-3 supplementation have some benefit in reversing cognitive decline in older adults, but they have not been investigated in survivors of childhood malnutrition.Hence, we propose to introduce a six month intervention of supervised aerobic exercise and omega-3 supplementation, and will compare cognitive function pre and post intervention/placebo between malnutrition survivors and controls.

This study builds evidence on the importance of using safe drinking water during the nutritional treatment of children affected by Severe Acute Malnutrition (SAM). The following hypotheses will be tested: 1.The addition of safe drinking water to SAM treatment will reduce exposure to pathogens that cause diarrhoeal disease, thereby reducing diarrhoea incidence among enrolled children. 2.Reductions in pathogen exposure and diarrhoeal disease will result in shorter recovery pe-riods for children with SAM. The study will evaluate the effectiveness of safe drinking water in reducing SAM treatment cost and duration and will provide recommendations for improving SAM treatment protocols.

Children with severe malnutrition who are admitted sick to hospitals have a high mortality(death rate), usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics(medication used to kill bacteria). However, the current antibiotics used in hospitals may not be the most effective. It is possible that the antibiotics that are currently used after initial antibiotics should be used first. No studies have been carried out to determine if the current antibiotics used for treating malnourished children who are sick and admitted in hospital are the most appropriate. The aim of this study is to find out if a changed antibiotic system for children with malnutrition is safe, reduces the risk of death and improves nutritional recovery.

The objective of this study is to determine the efficacity of a community strategy for screening children 06-59 months old for Severe Acute Malnutrition (SAM) conducted by their mothers' compared with a community screening strategy conducted by Community Health Workers.

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.

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: 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. 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: possible misdiagnosis of SAM made by MUAC or WHZ criteria, varying degree of severity and need for admission to treatment of the different types of diagnosis, 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.

It is unclear whether children with HIV and severe acute malnutrition can be started on highly active antiretroviral therapy (HAART) safely while they are still malnourished and the manner in which this therapy should start. This study will examine the safety, efficacy, and metabolism of children started on HAART while still severely malnourished.

The purpose of this study is to assesses the effectiveness of an integrated model for the management of severe acute malnutrition (IM-SAM) in India comprising facility- and community-based care and using locally-adapted protocols