Anti-inflammatory Effect of Pre-operative Stimulation of the Cholinergic Anti-Inflammatory Pathway

NCT02425774 | Completed Phase 4

• 1 other identifier: S56328
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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

Conditions

Postoperative Ileus

Keywords

Prucalopride; Vagus Nerve Stimulation; Postoperative Ileus

Outcome Measures

Primary Outcomes (1)

• Levels of pro-inflammatory cytokines in intestinal tissue, serum, peritoneal lavage and supernatant of stimulated whole blood

  From the date of surgery until the date of lab analysis (up to 6 months)

Secondary Outcomes (6)

• Time to first flatus

  From the date of surgery until the date of discharge from the hospital (on average 14 days)

• Time to tolerance of oral food intake

  From the date of surgery until the date of discharge from the hospital (on average 14 days)

• Time to tolerance of oral food intake AND first defecation

  From the date of surgery until the date of discharge from the hospital (on average 14 days)

• Time to first defecation

  From the date of surgery until the date of discharge from the hospital (on average 14 days)

• Gastrointestinal symptoms (nausea, pain, vomiting, bloating)

  From the date of surgery until the date of discharge from the hospital (on average 14 days)

Study Arms (3)

Sham stimulation + Placebo

PLACEBO COMPARATOR

* no stimulation * 1 placebo tablet at two different timepoints before surgery

Procedure: Sham stimulation; Drug: Placebo

Vagus stimulation + placebo

ACTIVE COMPARATOR

* Stimulation at the beginning and the end of the surgery * 1 placebo tablet at two different timepoints before surgery

Procedure: Vagus stimulation; Drug: Placebo

Prucalopride + sham stimulation

ACTIVE COMPARATOR

* 1 prucalopride tablet at two different timepoints before surgery * no stimulation

Procedure: Sham stimulation; Drug: Prucalopride

Interventions

Vagus stimulation PROCEDURE

Vagus stimulation + placebo

Sham stimulation PROCEDURE

Prucalopride + sham stimulation; Sham stimulation + Placebo

Prucalopride DRUG

Prucalopride + sham stimulation

Placebo DRUG

Sham stimulation + Placebo; Vagus stimulation + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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))

Sponsors & Collaborators

• KU Leuven: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (1)

University hospitals Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (3)

• 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.

  PMID: 10486602 BACKGROUND

• 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.

  PMID: 9833803 BACKGROUND

• 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.

  PMID: 30472681 DERIVED

MeSH Terms

Interventions

Vagus Nerve Stimulation; prucalopride

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Guy Boeckxstaens, M.D.

  Catholic University Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 24, 2015
• First Posted: April 24, 2015
• Study Start: July 1, 2014
• Primary Completion: February 27, 2016
• Study Completion: February 27, 2016
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

BE (1)