Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06609980
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-07
Brief Title:
Restoration of Antibiotics Related Infant Microbiota Perturbations by Autologous Fecal Transplant
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Fecal Microbiota Transplantation Autologous in Infants Treated with Antibiotics
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
aFMT-babies
Brief Summary:
Antibiotics are lifesaving therapeutic drugs which have been used by adults children and infants alike for decades There is an increase in global use of antibiotics over the course of lifetime and earlier in lifetime with some countries recording as high as 12 courses a year in children younger than two While antibiotics are successful in eradicating many pathogenic bacteria research has demonstrated significant effect on beneficial gut microbiota including long-lasting shift in the dynamics composition richness and maturity of the intestinal flora Microbiota alterations during early life including through antibiotics use as well as birth via C-section constitute a developmental perturbation which increases the risk of modern diseases of immune and metabolic dysfunction Strong epidemiological evidence suggests associations between early stressors of the microbiota and a number of common diseases such as obesity asthma allergies celiac disease and Type 1 Diabetes Furthermore excess antibiotic exposure is associated with the development of neurological and psychiatric disorders Currently no strategies exist to restore the microbiome other than reliance on spontaneous repair mechanism which often takes months in a healthy individual barring further antibiotic exposure Contrary to popular belief ingestion of probiotics particularly after antibiotics has been demonstrated to slow down the repair as it introduces an exogenous and massive amounts of only a few types of bacterial strains into a finely-tuned ecosystem of hundreds of different strains
It is hypothesized that by preserving the childs microbiome prior to antibiotic therapy and reintroducing it afterwards through an autologous fecal matter transplant FMT will assist in a quick effective and host-specific microbiome recolonization to the levels and patterns to those prior to antibiotics This would in turn reduce the overall loss of microbiome diversity over the childs lifespan essentially providing a reset option to the childs most unadulterated version of microbiome This approach utilizes delivering the sample by mixing it in maternal milk or formula and feeding it to the child through a bottle which can be performed anywhere without any discomfort for the child
It is hypothesized that by preserving the childs microbiome prior to antibiotic therapy and reintroducing it afterwards through an autologous fecal matter transplant FMT will assist in a quick effective and host-specific microbiome recolonization to the levels and patterns to those prior to antibiotics This would in turn reduce the overall loss of microbiome diversity over the childs lifespan essentially providing a reset option to the childs most unadulterated version of microbiome This approach utilizes delivering the sample by mixing it in maternal milk or formula and feeding it to the child through a bottle which can be performed anywhere without any discomfort for the child
Detailed Description:
Antibiotics are lifesaving therapeutic drugs which have been used by adults children and infants alike for decades There is an increase in global use of antibiotics over the course of lifetime and earlier in lifetime with some countries recording as high as 12 courses a year in children younger than two While antibiotics are successful in eradicating many pathogenic bacteria research has demonstrated significant effect on beneficial gut microbiota including long-lasting shift in the dynamics composition richness and maturity of the intestinal flora
Microbiota alterations during early life including through antibiotics use as well as birth via C-section constitute a developmental perturbation which increases the risk of modern diseases of immune and metabolic dysfunction Strong epidemiological evidence suggests associations between early stressors of the microbiota and a number of common diseases such as obesity asthma allergies celiac disease and Type 1 Diabetes There is evidence from mouse experiments of early perturbations in microbiota transmission at birth such as C-section birthing causing changes in the microbiome increasing weight gain and inhibiting intestinal expression of immune genes in neonates Furthermore excess antibiotic exposure is associated with the development of neurological and psychiatric disorders Given the tendency of early perturbations to increase disease risks it is important to evaluate effects of significant perturbations to microbiome at early ages such as through antibiotic use
Currently no strategies exist to restore the microbiome other than reliance on spontaneous repair mechanism which often takes months in a healthy individual barring further antibiotic exposure Modern lifestyle and urban environments however work against this spontaneous repair significantly reducing the microbiome diversity not only generationally but within an individuals lifespan Contrary to popular belief ingestion of probiotics particularly after antibiotics has been demonstrated to slow down the repair as it introduces an exogenous and massive amounts of only a few types of bacterial strains into a finely-tuned ecosystem of hundreds of different strains
It is hypothesized that by preserving the childs microbiome prior to antibiotic therapy and reintroducing it afterwards through an autologous fecal matter transplant FMT will assist in a quick effective and host-specific microbiome recolonization to the levels and patterns to those prior to antibiotics This would in turn reduce the overall loss of microbiome diversity over the childs lifespan essentially providing a reset option to the childs most unadulterated version of microbiome
FMTs have been utilized including in pediatric populations to successfully treat recurring Clostridium difficile infections and are being investigated further as an adjunctive treatment in the management of ulcerative colitis Crohns Disease and autism symptoms Administration of heterologous FMTs where recipient is different from donor however carry their own complexities - stool samples supplied by donors have to be identified and screened and are traditionally delivered in a medical setting as an out-patient procedure The heterologous FMTs performed today layer the process with additional steps of ideal donor identification and sample screening for possible transmissible pathogens This proposal uses an autologous sample which means the sample comes from the healthy child and is administered to the same child after infection and the antibiotic course conserving the absolutely unique diversity and heritage that that particular childs microbiome had before perturbation due to disease and antibiotics
In adults an FMT in form of a capsule for oral use has demonstrated equally successful treatment of C difficile infection as a rectally-delivered sample In children since they cannot swallow capsules FMTs are delivered as enemas and colonoscopies or through nasogastric and nasojejunal tubes which require significant resources for the administration of the procedure including anesthesia and observation in addition to the very likely stress impact on the patient
To evade the invasive nature of these deliveries novel systems through oral consumption have been investigated In C-section born infants maternal stool sample mixed in a bottle of milk and drank by the newborns restored normal gut microbial development to resemble that of vaginally-born babies The approach utilizes delivering the sample by mixing it in maternal milk or formula and feeding it to the child through a bottle which can be performed anywhere without any discomfort for the child
Early life microbiome preservation and restoration holds a tremendous therapeutic potential Similar to the idea of umbilical stem cells harvesting where stem cells are collected from the infants umbilical cord stored and used as autologous therapeutic transplants in certain cases of cancer preserved early-life microbiome could be used after antibiotic therapy to restore the composition of the microbiome to the pre-antibiotic state Unlike the umbilical stem cells harvesting however fecal sample collection and administration is considerably easier and the predicted chances for the need of restorative therapy almost certain Clinical success of such microbiome restorative therapy would exponentially decrease the loss of microbiome diversity and dynamics over ones lifetime and by extension decrease aforementioned associated risks
The study will be a correlational case-control study comparing the effects of autologous fecal matter transplant aFMT after antibiotic therapy on infant microbiome The recruitment will be of infants and toddlers up to 4 years of age and of caregivers to collect and freeze fecal samples once a month throughout the duration of the study The caregivers will be asked to notify the study team if the child has been administered antibiotics and after the therapy has ended the last collected sample prior to treatment will be used for autologous transplant by mixing the frozen infant fecal pellet in milk and administering it to the child The diversity and composition of the childs fecal microbiome prior and after the transplant will be compared and then compare those results with the microbiome of control group of children who have received antibiotics but no intervention
Microbiota alterations during early life including through antibiotics use as well as birth via C-section constitute a developmental perturbation which increases the risk of modern diseases of immune and metabolic dysfunction Strong epidemiological evidence suggests associations between early stressors of the microbiota and a number of common diseases such as obesity asthma allergies celiac disease and Type 1 Diabetes There is evidence from mouse experiments of early perturbations in microbiota transmission at birth such as C-section birthing causing changes in the microbiome increasing weight gain and inhibiting intestinal expression of immune genes in neonates Furthermore excess antibiotic exposure is associated with the development of neurological and psychiatric disorders Given the tendency of early perturbations to increase disease risks it is important to evaluate effects of significant perturbations to microbiome at early ages such as through antibiotic use
Currently no strategies exist to restore the microbiome other than reliance on spontaneous repair mechanism which often takes months in a healthy individual barring further antibiotic exposure Modern lifestyle and urban environments however work against this spontaneous repair significantly reducing the microbiome diversity not only generationally but within an individuals lifespan Contrary to popular belief ingestion of probiotics particularly after antibiotics has been demonstrated to slow down the repair as it introduces an exogenous and massive amounts of only a few types of bacterial strains into a finely-tuned ecosystem of hundreds of different strains
It is hypothesized that by preserving the childs microbiome prior to antibiotic therapy and reintroducing it afterwards through an autologous fecal matter transplant FMT will assist in a quick effective and host-specific microbiome recolonization to the levels and patterns to those prior to antibiotics This would in turn reduce the overall loss of microbiome diversity over the childs lifespan essentially providing a reset option to the childs most unadulterated version of microbiome
FMTs have been utilized including in pediatric populations to successfully treat recurring Clostridium difficile infections and are being investigated further as an adjunctive treatment in the management of ulcerative colitis Crohns Disease and autism symptoms Administration of heterologous FMTs where recipient is different from donor however carry their own complexities - stool samples supplied by donors have to be identified and screened and are traditionally delivered in a medical setting as an out-patient procedure The heterologous FMTs performed today layer the process with additional steps of ideal donor identification and sample screening for possible transmissible pathogens This proposal uses an autologous sample which means the sample comes from the healthy child and is administered to the same child after infection and the antibiotic course conserving the absolutely unique diversity and heritage that that particular childs microbiome had before perturbation due to disease and antibiotics
In adults an FMT in form of a capsule for oral use has demonstrated equally successful treatment of C difficile infection as a rectally-delivered sample In children since they cannot swallow capsules FMTs are delivered as enemas and colonoscopies or through nasogastric and nasojejunal tubes which require significant resources for the administration of the procedure including anesthesia and observation in addition to the very likely stress impact on the patient
To evade the invasive nature of these deliveries novel systems through oral consumption have been investigated In C-section born infants maternal stool sample mixed in a bottle of milk and drank by the newborns restored normal gut microbial development to resemble that of vaginally-born babies The approach utilizes delivering the sample by mixing it in maternal milk or formula and feeding it to the child through a bottle which can be performed anywhere without any discomfort for the child
Early life microbiome preservation and restoration holds a tremendous therapeutic potential Similar to the idea of umbilical stem cells harvesting where stem cells are collected from the infants umbilical cord stored and used as autologous therapeutic transplants in certain cases of cancer preserved early-life microbiome could be used after antibiotic therapy to restore the composition of the microbiome to the pre-antibiotic state Unlike the umbilical stem cells harvesting however fecal sample collection and administration is considerably easier and the predicted chances for the need of restorative therapy almost certain Clinical success of such microbiome restorative therapy would exponentially decrease the loss of microbiome diversity and dynamics over ones lifetime and by extension decrease aforementioned associated risks
The study will be a correlational case-control study comparing the effects of autologous fecal matter transplant aFMT after antibiotic therapy on infant microbiome The recruitment will be of infants and toddlers up to 4 years of age and of caregivers to collect and freeze fecal samples once a month throughout the duration of the study The caregivers will be asked to notify the study team if the child has been administered antibiotics and after the therapy has ended the last collected sample prior to treatment will be used for autologous transplant by mixing the frozen infant fecal pellet in milk and administering it to the child The diversity and composition of the childs fecal microbiome prior and after the transplant will be compared and then compare those results with the microbiome of control group of children who have received antibiotics but no intervention
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None