Clinical trial NCT02425774: Anti-inflammatory Effect of Pre-operative Stimulation of the Cholinergic Anti-Inflammatory Pathway
Official title: Anti-inflammatory Effect of Pre-operative Stimulation of the Cholinergic Anti-Inflammatory Pathway: A Potential New Therapeutical Intervention for Postoperative Ileus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Postoperative Ileus
Keywords: Prucalopride
Vagus Nerve Stimulation
Postoperative Ileus
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: Universitaire Ziekenhuizen KU Leuven
First posted: 2015-04-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypothesis:

Prucalopride can mimic electrical stimulation of the abdominal vagus nerve and has an anti-inflammatory effect.

Aims:

In the present pilot study, the investigators want to evaluate the anti-inflammatory effect of prucalopride. The following aims are formulated:

1. to show that prucalopride has a similar inflammatory effect as abdominal vagus nerve stimulation (VNS)
2. to evaluate whether prucalopride leads to accelerated post-operative recovery


Eligibility criteria: Inclusion Criteria:

* patients undergoing partial or full resection of the pancreas due to a benign or malignant tumor

Exclusion Criteria:

* adjuvant radiotherapy
* evident intra-abdominal inflammation (diagnosed by imaging and/or laboratory results, including an abscess or cholecystitis)
* chronic pancreatitis
* pancreatic polypeptide producing endocrine tumor
* American Society of Anesthesiologists physical-health status classification (ASA-PS)\>3
* Poorly regulated diabetes (\>200 mg/dl (=11 mmol/l))

Primary outcomes:
measure: Levels of pro-inflammatory cytokines in intestinal tissue, serum, peritoneal lavage and supernatant of stimulated whole blood
timeFrame: From the date of surgery until the date of lab analysis (up to 6 months)
Secondary outcomes:
measure: Time to first flatus
timeFrame: From the date of surgery until the date of discharge from the hospital (on average 14 days)
measure: Time to tolerance of oral food intake
timeFrame: From the date of surgery until the date of discharge from the hospital (on average 14 days)
measure: Time to tolerance of oral food intake AND first defecation
timeFrame: From the date of surgery until the date of discharge from the hospital (on average 14 days)
measure: Time to first defecation
timeFrame: From the date of surgery until the date of discharge from the hospital (on average 14 days)
measure: Gastrointestinal symptoms (nausea, pain, vomiting, bloating)
timeFrame: From the date of surgery until the date of discharge from the hospital (on average 14 days)
measure: Time to discharge from the hospital
timeFrame: From the date of surgery until the date of discharge from the hospital (on average 14 days)
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University hospitals Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Catholic University Leuven
name: Guy Boeckxstaens, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kalff JC, Buchholz BM, Eskandari MK, Hierholzer C, Schraut WH, Simmons RL, Bauer AJ. Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat. Surgery. 1999 Sep;126(3):498-509.
citation: Kalff JC, Schraut WH, Simmons RL, Bauer AJ. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg. 1998 Nov;228(5):652-63. doi: 10.1097/00000658-199811000-00004.
citation: Stakenborg N, Labeeuw E, Gomez-Pinilla PJ, De Schepper S, Aerts R, Goverse G, Farro G, Appeltans I, Meroni E, Stakenborg M, Viola MF, Gonzalez-Dominguez E, Bosmans G, Alpizar YA, Wolthuis A, D'Hoore A, Van Beek K, Verheijden S, Verhaegen M, Derua R, Waelkens E, Moretti M, Gotti C, Augustijns P, Talavera K, Vanden Berghe P, Matteoli G, Boeckxstaens GE. Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons. Gut. 2019 Aug;68(8):1406-1416. doi: 10.1136/gutjnl-2018-317263. Epub 2018 Nov 24.