Protease Activated Receptor-2 and Gastrointestinal Dysfunction in Critical Illness

NCT03011151 | Completed

• 1 other identifier: IRB-P00024070
• Study Type: observational
• Target: 99
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastroparesis; Gastrointestinal Disorder, Functional; Critical Illness

Keywords

pediatric; critical illness; surgery; gastrointestinal dysfunction; gastric emptying; epithelial barrier; nutrition

Outcome Measures

Primary Outcomes (2)

• PAR2 agonist activity- serum zonulin

  PAR2 agonist activity will be measured by serum zonulin levels (ng/mL)

  Immediately pre-operative versus post-operative day 1

• PAR2 agonist activity- fecal protease activity

  PAR2 agonist activity will be measured by fecal serine protease activity (trypsin units/gm protein)

  Immediately pre-operative versus post-operative day 1

Secondary Outcomes (2)

• Gastric motility by the acetaminophen absorption test- AUC

  Immediately pre-operative versus post-operative day 1

• Epithelial barrier integrity by serum biomarkers

  Immediately pre-operative versus post-operative day 1

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children undergoing posterior spinal fusion and admitted to the pediatric intensive care unit

You may qualify if:

• years and older

You may not qualify if:

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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Martinez EE, Zurakowski D, Pereira L, Freire R, Emans JB, Nurko S, Duggan CP, Fasano A, Mehta NM. Interleukin-10 and Zonulin Are Associated With Postoperative Delayed Gastric Emptying in Critically Ill Surgical Pediatric Patients: A Prospective Pilot Study. JPEN J Parenter Enteral Nutr. 2020 Nov;44(8):1407-1416. doi: 10.1002/jpen.1874. Epub 2020 Jun 3.

  PMID: 32386238 RESULT

• Martinez EE, Lan J, Konno T, Miranda-Ribera A, Fiorentino M, Mehta NM, Fasano A. Novel role of zonulin in the pathophysiology of gastro-duodenal transit: a clinical and translational study. Sci Rep. 2021 Nov 17;11(1):22462. doi: 10.1038/s41598-021-01879-y.

  PMID: 34789790 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, Stool

MeSH Terms

Conditions

Gastroparesis; Gastrointestinal Diseases; Critical Illness

Condition Hierarchy (Ancestors)

Stomach Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Study Officials

• Enid Martinez, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant in Critical Care Medicine

Study Record Dates

• First Submitted: January 2, 2017
• First Posted: January 5, 2017
• Study Start: August 1, 2017
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)