Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06547424
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-07
Brief Title:
Phase I Clinical Study of Chondroitin Sulfate for Treatment of NEC
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Randomized Controlled Double-Blind Phase I Clinical Study of Chondroitin Sulfate Supplementation for Treatment of Necrotizing Enterocolitis
Status:
NOT_YET_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:
None
Brief Summary:
The goal of this phase 1 double blind randomized controlled trial is to determine the safety of chondroitin sulfate supplementation in the neonates with necrotizing enterocolitis The main questions the study aims to answer are
Is chondroitin sulfate safe to administer in the neonatal NEC population and will it have a beneficial profile in the short term intestinal and long term neurodevelopmental sequelae of NEC Researchers will compare all cause mortality progression to surgery systemic inflammatory markers and long term neurodevelopmental outcomes in those NEC patients who receive chondroitin sulfate compared to those who receive milk or formula placebo
Is chondroitin sulfate safe to administer in the neonatal NEC population and will it have a beneficial profile in the short term intestinal and long term neurodevelopmental sequelae of NEC Researchers will compare all cause mortality progression to surgery systemic inflammatory markers and long term neurodevelopmental outcomes in those NEC patients who receive chondroitin sulfate compared to those who receive milk or formula placebo
Detailed Description:
Necrotizing Enterocolitis NEC is a devastating intra-abdominal emergency that primarily affects premature infants and is characterized by abdominal distention extreme illness and intestinal necrosis-with mortality rates that range from 20-30 Despite earnest research there have been no significant advances in our ability to treat this disease within the last several decades making NEC an unmet medical need
Neurodevelopmental impairment NDI is a detrimental sequela in infants with NEC and carries an incidence of approximately 40 NDI is believed to be a result of the systemic inflammatory response and pathogenic signaling cascades associated with NEC resulting in white-matter injury alterations in brain parenchyma and loss of brain matter volume-which then manifest in later life as cognitive and motor deficits autism and cerebral palsy Novel therapeutic strategies to treat or prevent NEC and its long-term sequelae would have a significant impact on reducing morbidity and mortality in this fragile population
Our long-term goal is to develop effective methods for the prevention and treatment of NEC and its neurodevelopmental sequelae In this regard the use of human breast milk HM is an important preventative strategy to reduce the incidence of NEC In one study 72 of infants receiving formula developed NEC while only 12 of infants exclusively being fed breastmilk developed NEC This would suggest that protective compounds exist in human breastmilk that may prevent NEC However despite the beneficial properties of human breastmilk its important to note that breast milk has not been shown to eliminate NEC Therefore finding protective compounds in HM that could be utilized as a formula additive or breast milk booster would be highly effective in further preventing and treating NEC A prominent glycosoaminoglycan gaining clinical interest is chondroitin sulfate CS which comprises over half of the normal GAG content in HM and is surprisingly nonexistent in most major infant formulas Additionally the concentration of CS in HM is higher in preterm mothers than in term mothers thereby suggesting some evolutionary importance for this compound to preterm infants6
A review of the prior rigor of research suggests that CS decreases blood lipopolysaccharide LPS levels in mice experiencing stress reduces invasion and translocation of bacteria within the intestine restores repressed fecal short-chain fatty acids and alters the intestinal microbiome We have appreciated beneficial effects of CS in protecting the intestine during experimental NEC A possible mechanism of action surrounds its modulation of the Th17 immune cell profile An increase in Th17 cells and intestinal NFĸΒ phosphorylation has long been recognized as contributing molecular factors in NEC Furthermore IL-17 is an important effector cytokine of Th17 cells and is involved in the pathogenesis of acute neuroinflammatory conditions
The overarching goal of this project is to perform a randomized controlled double blind phase 1 clinical trial to assess the short- and long-term safety profiles of chondroitin sulfate for the treatment of necrotizing enterocolitis in the neonatal population Preliminary data from murine and porcine animal models in our lab have shown protection against the intestinal and neurodevelopmental sequelae of NEC CS has previously been considered a food supplement and therefore is not regulated by the FDA It has been classified as Generally Recognized as Safe by the FDA and has been used in adult clinical trials without increased safety concerns We therefore hypothesize that CS will be safe to administer in the neonatal NEC population and will have a beneficial safety profile in the short term intestinal and long term neurodevelopmental sequela of NEC To test these hypotheses we propose the following Specific Aims
1 Assess the short-term safety profile of CS supplementation in the neonatal NEC population and its impact on mortality progression to surgery and the systemic inflammatory profile Adverse events progression to surgery and all-cause mortality will be assessed in preterm low birth weight infants with Bells Stage II NEC Additionally the ability of CS to modulate the immune cell profile and systemic inflammatory response will be assessed
2 Determine the impact of chondroitin sulfate supplementation on neurodevelopmental outcomes in the NEC population as a marker of long-term safety To assess long-term safety neurodevelopmental impairment of infants receiving CS will be compared to placebo at both 1- and 2-years following administration We hypothesize that CS infants would have similar if not improved NDI compared to placebo
Neurodevelopmental impairment NDI is a detrimental sequela in infants with NEC and carries an incidence of approximately 40 NDI is believed to be a result of the systemic inflammatory response and pathogenic signaling cascades associated with NEC resulting in white-matter injury alterations in brain parenchyma and loss of brain matter volume-which then manifest in later life as cognitive and motor deficits autism and cerebral palsy Novel therapeutic strategies to treat or prevent NEC and its long-term sequelae would have a significant impact on reducing morbidity and mortality in this fragile population
Our long-term goal is to develop effective methods for the prevention and treatment of NEC and its neurodevelopmental sequelae In this regard the use of human breast milk HM is an important preventative strategy to reduce the incidence of NEC In one study 72 of infants receiving formula developed NEC while only 12 of infants exclusively being fed breastmilk developed NEC This would suggest that protective compounds exist in human breastmilk that may prevent NEC However despite the beneficial properties of human breastmilk its important to note that breast milk has not been shown to eliminate NEC Therefore finding protective compounds in HM that could be utilized as a formula additive or breast milk booster would be highly effective in further preventing and treating NEC A prominent glycosoaminoglycan gaining clinical interest is chondroitin sulfate CS which comprises over half of the normal GAG content in HM and is surprisingly nonexistent in most major infant formulas Additionally the concentration of CS in HM is higher in preterm mothers than in term mothers thereby suggesting some evolutionary importance for this compound to preterm infants6
A review of the prior rigor of research suggests that CS decreases blood lipopolysaccharide LPS levels in mice experiencing stress reduces invasion and translocation of bacteria within the intestine restores repressed fecal short-chain fatty acids and alters the intestinal microbiome We have appreciated beneficial effects of CS in protecting the intestine during experimental NEC A possible mechanism of action surrounds its modulation of the Th17 immune cell profile An increase in Th17 cells and intestinal NFĸΒ phosphorylation has long been recognized as contributing molecular factors in NEC Furthermore IL-17 is an important effector cytokine of Th17 cells and is involved in the pathogenesis of acute neuroinflammatory conditions
The overarching goal of this project is to perform a randomized controlled double blind phase 1 clinical trial to assess the short- and long-term safety profiles of chondroitin sulfate for the treatment of necrotizing enterocolitis in the neonatal population Preliminary data from murine and porcine animal models in our lab have shown protection against the intestinal and neurodevelopmental sequelae of NEC CS has previously been considered a food supplement and therefore is not regulated by the FDA It has been classified as Generally Recognized as Safe by the FDA and has been used in adult clinical trials without increased safety concerns We therefore hypothesize that CS will be safe to administer in the neonatal NEC population and will have a beneficial safety profile in the short term intestinal and long term neurodevelopmental sequela of NEC To test these hypotheses we propose the following Specific Aims
1 Assess the short-term safety profile of CS supplementation in the neonatal NEC population and its impact on mortality progression to surgery and the systemic inflammatory profile Adverse events progression to surgery and all-cause mortality will be assessed in preterm low birth weight infants with Bells Stage II NEC Additionally the ability of CS to modulate the immune cell profile and systemic inflammatory response will be assessed
2 Determine the impact of chondroitin sulfate supplementation on neurodevelopmental outcomes in the NEC population as a marker of long-term safety To assess long-term safety neurodevelopmental impairment of infants receiving CS will be compared to placebo at both 1- and 2-years following administration We hypothesize that CS infants would have similar if not improved NDI compared to placebo
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