Protease Activated Receptor-2 and Gastrointestinal Dysfunction in Critical Illness
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital, Gastrointestinal, Gastrointestinal, Digestive Disease |
| Therapuetic Areas: | Gastroenterology, Other |
| Healthy: | No |
| Age Range: | 2 - 30 |
| Updated: | 7/19/2018 |
| Start Date: | August 1, 2017 |
| End Date: | December 31, 2019 |
| Contact: | Enid Martinez, MD |
| Email: | enid.martinez@childrens.harvard.edu |
| Phone: | 6173557327 |
Examining the Role of Protease-activated Receptor 2 Agonists in Gastrointestinal Dysfunction in Pediatric Surgical Critical Illness
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.
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.
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.
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.
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
We found this trial at
1
site
300 Longwood Ave
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 355-6000
Phone: 617-355-7327
Boston Children's Hospital Boston Children's Hospital is a 395-bed comprehensive center for pediatric health care....
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