Active clinical trials for "Severe Acute Malnutrition"

HYPOTHESIS: Investigators hypothesize that by provision of care at household level in a community through lady health workers will as effective (recovery rate, burden of SAM, cost effective, coverage) as through health care providers at facility level. OBJECTIVES To evaluate the effectiveness (rate of recovery, burden & coverage), of SAM standard management of children 06-59 months delivered at household level by first level health care providers (Lady health workers) compared with the standard CMAM program delivered at health facility by Govt./ACF staff. To evaluate the cost effectiveness of treatment of SAM provided by LHWs at community level versus treatment delivered at health facility by Govt/ACF staff. STUDY DESIGN: Cluster randomized controlled trial SAMPLE SIZE & RANDOMIZATION: Investigators took 6% prevalence to calculate the sample size with an expected reduction of 20%. A sample size of 3 clusters per group with 150 individuals per cluster is needed. STUDY METHODOLOGY Intervention (Group A): LHWs will identify and treat all cases of severe acute malnutrition (SAM) as per the study eligibility criteria (MUAC < 11.5 cm) and manage all cases of SAM without complications at home following the national CMAM guidelines. Control (Group B): LHWs will identify SAM as per the CMAM guidelines (MUAC < 11.5 cm) and will refer all cases to the health facility (ACF) for further management and counselling by health workers at facility.

In Burkina Faso the number of severely acute malnourished (SAM) children successfully treated has increased since the implementation of community-based management of acute malnutrition. SAM children with oedema have a higher risk of dying than SAM without oedema; they require inpatient care. Several theories have been proposed to explain the pathophysiology of oedema in SAM, but its etiology remains unclear. Knowledge on the nutritional adequacy of therapeutic regimens in kwashiorkor is limited. The World Health Organization (WHO) recommends to use in the treatment of complicated SAM a therapeutic milk 'F75' in the stabilization phase; F75+ready-to-use therapeutic foods (RUTF) or F100 at the transition phase. Alternatively the local formulas (maize flour, milk powder, oil, sugar, mineral-vitamin complex CMV) can be used in case of shortage or intolerance. At the Nutritional Rehabilitation and Education Center of the University Hospital of Bobo Dioulasso it was found that some SAM children whose oedema resolved under F75 in the stabilization phase, re-developed oedema as they entered the transition phase with RUTF. RUTF has the same nutritional value as F100 but contains iron unlike F100 (<0.07 mg/100 mL). It was observed that RUTF in some cases may be associated with higher mortality, probably due to high iron content (10-14 mg/100 g), which may increase the risk of infections and the formation of free radicals, thereby increasing damage to the body's cells. Clinical trials evaluating the current guidelines for the treatment of SAM with oedema are scarce. A better understanding of the risk factors affecting the effectiveness of the nutritional therapeutic protocol for children with Kwashiorkor will be useful to improve their care. The main objective of this study is to determine whether the use of transition phase diets (Plumpy-Nut®+F75 or F100 or alternative F75+/- CMV+ Plumpy-Nut®) affect oedema resolving in Kwashiorkor children and to investigate the underlying factors for the relapse or non-responsiveness to the therapeutic treatment.

Inpatient treatment for complicated severe acute malnutrition (SAM) continues to have a high mortality in Africa. This is partly because children are commonly brought for admission because they are seriously ill, rather than being brought to hospital because of malnutrition alone. Mortality rates are especially high where SAM is complicated by HIV or TB. The early phase of inpatient nutritional treatment for severe acute malnutrition is based on a low-protein milk known as F75, which is given to improve metabolic homeostasis prior to the re-feeding to achieve catch-up growth. F75 provides a high proportion of energy from carbohydrates, including sucrose, lactose and maltodextrin. However, malabsorption of different types of carbohydrates, but lactose in particular, is known to occur in SAM and may lead to osmotic diarrhoea. Diarrhoea is common in children with SAM and is associated with increased mortality. Furthermore, switching from a catabolic state to a high energy diet that consists of predominantly carbohydrates can lead to 're-feeding syndrome' that may lead to severe electrolyte abnormalities and multiple organ dysfunction. The aim of this trial is to determine whether reducing the carbohydrate content of F75, and removing lactose, improves the stabilisation of severely malnourished children. The trial will involve randomising children who are eligible to receive F75 milk to either the current formulation or a revised formulation. Both formulations will be given according to current recommendations regarding frequency of feeding and caloric value. Since the purpose of F75 is to stabilise the child metabolically and biochemically, the primary endpoint of the trial will be time to stabilisation (the end of the first phase of treatment for severe acute malnutrition). Blood and stool samples at admission and after three days will be used to determine the effects on carbohydrate and fat malabsorption and evidence of the re-feeding syndrome. Children will be followed up until discharge from hospital. The project has been planned in consultation with the World Health Organisation (WHO) and, if the revised formulation of F75 results in improved outcomes, will lead to a global change in recommendations for its formulation.

The general objective of the study is to answer to the question: "Is the current dose of AL less efficacious in the severely malnourished compared to the non-severely malnourished children, and is PK in cause?" We aim to assess whether the current treatment dose is adequate for children with severe acute malnutrition, and we hope results will guide further recommendations for malaria treatment in this specific population.

Severe wasting or Severe Acute Malnutrition (SAM) continues to be a major public health problem in Indonesia, affecting more than 2 million children under 5 years old. A new approach to treat SAM is called Community-based management of acute malnutrition (CMAM), which has been designed to maximize the coverage and successful treatment of children with SAM, by providing Ready to Use Therapeutic Food (RUTF) through out-patient treatment. Since 2019, UNICEF has been working intensively to facilitate the local production of RUTF. This present study aims to assess the acceptability and efficacy of three locally produced RUTFs compared to the standard peanut based RUTF. The study will be implemented in Bogor district. A total of 300 children with uncomplicated SAM, aged 6-59 months old, meeting the inclusion criteria will be included in the study. This study is designed as a randomized controlled trial. The children will be allocated to one of the five intervention (1 control, 4 experimental) arms. Each child will receive one type of RUTF product for eight consecutive weeks. The ration given to a child will be based on the need for an intake of ~ 170 kcal/kg BW/day. Data will be collected at baseline, at weekly intervals and at exit. The primary outcome of interest for the efficacy study is the relative weight gain of children consuming each of the local RUTFs compared with those consuming the standard RUTF. The primary outcome of the acceptability of the RUTFs will be the amount of product consumed during the eight-week efficacy trial. Differences in weight and height gain will be analyzed using ANCOVA, controlling for age, gender, food intake, and morbidity. Repeated measurement statistics will be used to analyze differences in growth patterns over the eight-week intervention.

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.

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.

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.

An appropriate balance of omega-6 and omega-3 fatty acids is important for support of neurocognitive development in healthy infants and toddlers. In young children recovering from severe acute malnutrition (SAM), excess omega-6 intake depletes omega-3 fatty acid status. This research will evaluate how novel ready-to-use therapeutic foods (RUTF) with balanced fatty acids improve the metabolic and neurocognitive effects in young children in Malawi recovering from SAM, yielding new knowledge that also has implications for development of well-nourished children.

Children with complicated severe acute malnutrition (SAM), such as inability to take adequate feeds, infection and diarrhoea, require in-patient management. Despite following a well-established World Health Organisation (WHO) protocol, outcomes are poor. Case fatality often exceeds 20%. Amongst survivors discharged home, many subsequently die, have long-term poor growth or recurrence of SAM. It has long been recognized that children with SAM have intestinal inflammation and that this persists despite management according to WHO guidelines. The inflammation is thought to result from increased exposure to microbial pathogens in the gut in areas with poor sanitation. The damaged lining of the intestine impairs food digestion and absorption, likely allows gut bacteria to enter the blood stream to cause sepsis and also exposes the gut immune cells to microbial and food antigens causing the inflammation to persist. Failure to treat the intestinal inflammation is likely to contribute to the poor response to treatment and poor long-term outcomes in many children with SAM. The intestinal inflammation seen in SAM is very similar to that which occurs in food intolerance (e.g. intolerance to cow's milk protein) and inflammatory bowel disease. In these conditions, the inflammation is treated very effectively with hypoallergenic ("elemental") and anti-inflammatory ("polymeric") formulas. These are nutritionally complete feeds that have a similar composition to the feeds used for nutritional rehabilitation in SAM. We aim to undertake a pilot study to see if an elemental and/or polymeric formula are tolerated by children with SAM and help to reduce intestinal inflammation. We also aim to learn more about the intestinal inflammation in general that occurs in SAM by observing carefully the effect of these specific formulae and to do in-depth metabolic analyses.