Ignite Creation Date:
2024-05-06 @ 6:00 PM
Last Modification Date:
2024-10-26 @ 2:39 PM
Study NCT ID:
NCT05501470
Status:
RECRUITING
Last Update Posted:
2024-06-21
First Post:
2022-08-04
Brief Title:
Probiotic For the Improvement of Environmental Enteropathy in Pregnant Women in Senegal
Sponsor:
Institut Pasteur de Dakar
Organization:
Institut Pasteur de Dakar
Study Overview
Official Title:
Ability of the Probiotic Vivomixx to Improve Environmental Enteropathy in Pregnant Women a Proof of Concept Trial in Senegal
Status:
RECRUITING
Status Verified Date:
2024-05
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:
PROFE-Sen
Brief Summary:
Stunting in young children refers to attenuated linear growth In the year 2020 1492 million children under the age of 5 were stunted accounting for 22 of stunting globally Stunting has short- and long-term consequences of increased morbidity and mortality impairment of neurocognitive development impaired responses to oral vaccines and increased risk of non-communicable diseases Stunting is partly driven by Environmental Enteric Dysfunction EED an enteropathic condition characterised by altered gut permeability infiltration of immune cells and changes in villous architecture and cell differentiation EED may help explain why nutritional supplementation either during pregnancy or early childhood has minimal value in correcting childhood stunting
Probiotics may serve to overcome the problem of EED through all mechanisms of pathogenicity by providing additional bacteria that may help in intestinal decolonization of pathogenic microorganisms changing the microbiological niche promoting epithelial healing improving nutrient absorption and restoration of an appropriate immune balance between tolerance and responsiveness
This trial will explore the conceptual framework that a well known probiotic that can improve the composition of the gut microbiota can reduce biomarkers of intestinal inflammation and gut health This will restore healthy microbial signalling to the host epithelium ameliorate barrier function through secretion of mucus and antimicrobial factors and improve nutrient availability
Probiotics may serve to overcome the problem of EED through all mechanisms of pathogenicity by providing additional bacteria that may help in intestinal decolonization of pathogenic microorganisms changing the microbiological niche promoting epithelial healing improving nutrient absorption and restoration of an appropriate immune balance between tolerance and responsiveness
This trial will explore the conceptual framework that a well known probiotic that can improve the composition of the gut microbiota can reduce biomarkers of intestinal inflammation and gut health This will restore healthy microbial signalling to the host epithelium ameliorate barrier function through secretion of mucus and antimicrobial factors and improve nutrient availability
Detailed Description:
Stunting in young children refers to attenuated linear growth In the year 2020 1492 million children under the age of 5 years of age were stunted accounting for 22 of stunting globally Stunting has short- and long-term consequences of increased morbidity and mortality impairment of neurocognitive development5 impaired responses to oral vaccines and increased risk of non-communicable diseases Stunting is partly driven by Environmental Enteric Dysfunction EED an enteropathic condition characterised by altered gut permeability infiltration of immune cells and changes in villous architecture and cell differentiation EED may help explain why nutritional supplementation either during pregnancy or early childhood has minimal value in correcting childhood stunting Indeed EED is believed to be responsible for 40 of childhood stunting Disruption in intestinal barrier function affects gut immune homeostasis nutrient flows and consequently dysbiosis in the gut microbiome The gut microbiota consists of 100 trillion bacteria which interact with epithelial cells the mucus layer and the mucosal immune system that balances tolerance and effector functions Thus the gut microbiome has an important role in shaping the responsiveness of the gut immune system The mucus barrier and the normal gut microbiota limit enteropathogen colonisation Influx of bacteria from the lumen to the systemic circulation represents microbial translocation and initiation of systemic of inflammatory process through recognition of pathogen-associated molecular patterns PAMPs by Pattern Recognition Receptors PRRs present on Antigen Presenting Cells APCs Three fundamental processes drive the epithelial damage which is so important in EED infection undernutrition and immune dysfunction Multiple clinical trials show that efforts to correct malnutrition through conventional therapies and improving hygiene and sanitation do not overcome growth deficits by more than about 10 There is increasing interest in the use of probiotics which may allow pathogen decolonization improve barrier function and restore overall gut homeostasis Such therapies are at early stage of trials but may have potential in addressing the global burden of EED by improving barrier function and gut pathophysiology
Colonization of gut by enteropathogens is common in children with EED These include ETEC Campylobacter Shigella and Salmonella species Consistent data from Bangladesh and Zambia show that children with refractory stunting carry over four pathogens on average whilst controls carry less than two There is also clear evidence of altered composition of the microbiota in children with EED
Probiotics may serve to overcome the problem of EED through all mechanisms of pathogenicity by providing additional bacteria that may help in intestinal decolonization of pathogenic microorganisms changing the microbiological niche promoting epithelial healing improving nutrient absorption and restoration of an appropriate immune balance between tolerance and responsiveness
To date the focus of research on childhood stunting has been on the young child It is increasingly appreciated however that stunting often begins in utero and the focus has shifted to womens health and pregnancy For example the Lancet 2021 Series on maternal and child undernutrition states that Investments to reduce undernutrition in women are important not only for womens own health but also for the health and nutrition of their children Results from rural Bangladesh reveal poor gestational weight gain that ultimately leads to intrauterine growth restriction low birth weight and ultimately stunting and wasting Furthermore another study recently completed in slum settlements of Dhaka Bangladesh demonstrated a high prevalence of EED among undernourished women Intestinal histopathology was abnormal in more than 80 of women We postulate that growth retardation in utero is a consequence of EED in the mother during pregnancy and lactation This leads to systemic inflammation which leads to disadvantageous partitioning of nutrients and reduced nutrient availability
This trial will explore the conceptual framework that a well known probiotic that can improve the composition of the gut microbiota can reduce biomarkers of intestinal inflammation and gut health This will restore healthy microbial signalling to the host epithelium ameliorate barrier function through secretion of mucus and antimicrobial factors and improve nutrient availability
The primary objective of this trial is to determine if a probiotic Vivomixx can reduce inflammation and epithelial damage in pregnant women with environmental enteropathy in the target countries
The secondary objectives of this trial are
To determine if Vivomixx can reduce enteropathogen colonisation To determine if Vivomixx can impact the structure and function of the microbiome To determine if Vivomixx can reduce permeability To determine if Vivomixx can impact the host metabolome in pregnant woman To evaluate variability in endpoints across geographies and participating laboratories
Colonization of gut by enteropathogens is common in children with EED These include ETEC Campylobacter Shigella and Salmonella species Consistent data from Bangladesh and Zambia show that children with refractory stunting carry over four pathogens on average whilst controls carry less than two There is also clear evidence of altered composition of the microbiota in children with EED
Probiotics may serve to overcome the problem of EED through all mechanisms of pathogenicity by providing additional bacteria that may help in intestinal decolonization of pathogenic microorganisms changing the microbiological niche promoting epithelial healing improving nutrient absorption and restoration of an appropriate immune balance between tolerance and responsiveness
To date the focus of research on childhood stunting has been on the young child It is increasingly appreciated however that stunting often begins in utero and the focus has shifted to womens health and pregnancy For example the Lancet 2021 Series on maternal and child undernutrition states that Investments to reduce undernutrition in women are important not only for womens own health but also for the health and nutrition of their children Results from rural Bangladesh reveal poor gestational weight gain that ultimately leads to intrauterine growth restriction low birth weight and ultimately stunting and wasting Furthermore another study recently completed in slum settlements of Dhaka Bangladesh demonstrated a high prevalence of EED among undernourished women Intestinal histopathology was abnormal in more than 80 of women We postulate that growth retardation in utero is a consequence of EED in the mother during pregnancy and lactation This leads to systemic inflammation which leads to disadvantageous partitioning of nutrients and reduced nutrient availability
This trial will explore the conceptual framework that a well known probiotic that can improve the composition of the gut microbiota can reduce biomarkers of intestinal inflammation and gut health This will restore healthy microbial signalling to the host epithelium ameliorate barrier function through secretion of mucus and antimicrobial factors and improve nutrient availability
The primary objective of this trial is to determine if a probiotic Vivomixx can reduce inflammation and epithelial damage in pregnant women with environmental enteropathy in the target countries
The secondary objectives of this trial are
To determine if Vivomixx can reduce enteropathogen colonisation To determine if Vivomixx can impact the structure and function of the microbiome To determine if Vivomixx can reduce permeability To determine if Vivomixx can impact the host metabolome in pregnant woman To evaluate variability in endpoints across geographies and participating laboratories
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