Clinical trial NCT03011151: Protease Activated Receptor-2 and Gastrointestinal Dysfunction in Critical Illness
Official title: Examining the Role of Protease-activated Receptor 2 Agonists in Gastrointestinal Dysfunction in Pediatric Surgical Critical Illness
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Gastroparesis
Gastrointestinal Disorder, Functional
Critical Illness
Keywords: pediatric
critical illness
surgery
gastrointestinal dysfunction
gastric emptying
epithelial barrier
nutrition
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2017-01-05
Enrollment: 80
Sex: ALL
Minimum age (years): 2
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children undergoing posterior spinal fusion and admitted to the pediatric intensive care unit

Brief summary: Gastrointestinal (GI) dysfunction affects up to 50% of medical and surgical critically ill children. GI dysfunction, specifically gastric dysmotility and loss of epithelial barrier integrity, is associated with significant morbidity in critical illness. The mechanisms underlying GI dysfunction in critical illness are not well understood. GI dysfunction in surgery and critical illness has been associated with inflammation. There is evidence to suggest the protease-activated receptor 2 (PAR2) is a link between inflammation and GI dysfunction. PAR2 is a G-coupled receptor present throughout the GI tract. PAR2 mediates GI motility and epithelial barrier integrity. PAR2 is activated by PAR2 agonists, specifically GI serine proteases and zonulin, released under conditions of inflammation. In this study the investigators will examine the relationship between inflammation and PAR2 activation by PAR2 agonists and subsequent GI dysfunction in pediatric critically ill surgical patients. The overall hypothesis of this study is that PAR2 activation by PAR2 agonists, GI serine proteases and zonulin, released due to inflammation results in gastric dysmotility and loss of epithelial barrier integrity. In this study, the investigators will examine whether PAR2 agonist expression is increased and correlates with GI dysfunction in critically ill surgical pediatric patients. This proposal fills a knowledge gap in the understanding of mechanisms for GI dysfunction in critical illness, and will be applicable to all surgical and medical critically ill children.

Detailed description: The investigators in this study aim to examine a plausible mechanism by which gastrointestinal dysfunction, gastric dysmotility and loss of epithelial barrier integrity, occur in critical illness. Specifically, the investigators will examine whether an increase in PAR2 agonist levels, zonulin and serine proteases, are associated with gastric dysmotility and loss of epithelial barrier integrity in critical surgical illness in children. The investigators will examine GI function, gastric motility and epithelial barrier integrity, and PAR2 agonist levels, zonulin and serine protease, in participants before surgery and after surgery. Specifically, children undergoing posterior spinal fusion, a known significant inflammatory trigger, and with planned admissions to the intensive care unit will be enrolled. Gastrointestinal function and PAR2 agonist levels will be tested non-invasively in blood and stool.

Eligibility criteria: Inclusion Criteria:

* 2 years and older

Exclusion Criteria:

* Liver dysfunction
* Renal dysfunction
* Pre-diagnosed gastroparesis/ delayed gastric emptying
* Pre-diagnosed gastrointestinal malabsorption
* Contraindication to acetaminophen administration

Primary outcomes:
measure: PAR2 agonist activity- serum zonulin
timeFrame: Immediately pre-operative versus post-operative day 1
measure: PAR2 agonist activity- fecal protease activity
timeFrame: Immediately pre-operative versus post-operative day 1
Secondary outcomes:
measure: Gastric motility by the acetaminophen absorption test- AUC
timeFrame: Immediately pre-operative versus post-operative day 1
measure: Gastric motility by the acetaminophen absorption test- Tmax
timeFrame: Immediately pre-operative versus post-operative day 1
measure: Gastric motility by the acetaminophen absorption test- Cmax
timeFrame: Immediately pre-operative versus post-operative day 1
measure: Epithelial barrier integrity by serum biomarkers
timeFrame: Immediately pre-operative versus post-operative day 1
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Enid Martinez, MD
role: PRINCIPAL_INVESTIGATOR
References: