Effect of Perioperative Neurostimulation in Patients Undergoing Whipple Operation (Pancreaticoduodenectomy) on Acute Postsurgical Inflammatory Response [ENSWAPI-trial]

NCT05743530 | Unknown

• 1 other identifier: ENSWAPI
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to test whether electrical stimulation of the vagus nerve via a device placed on the top of the external ear can reduce the postoperative inflammatory reaction after Whipple's surgery (pancreatoduodenectomy).

Conditions

Pancreaticoduodenectomy

Outcome Measures

Primary Outcomes (1)

• IL-6 levels change

  IL-6 levels change between baseline and postoperative day 1. Baseline is defines as the serum concentration IL-6 at 24h prior to surgery

  Baseline and postoperative day 1

Secondary Outcomes (27)

• Post surgical inflammatory response (IL-1)

  before surgery, day 1 and day 4 after surgery

• Post surgical inflammatory response (IL-6)

  before surgery, day 1 and day 4 after surgery

• Post surgical inflammatory response (IL-8)

  before surgery, day 1 and day 4 after surgery

• Post surgical inflammatory response (IL-13)

  before surgery, day 1 and day 4 after surgery

• Post surgical inflammatory response (IL-10)

  before surgery, day 1 and day 4 after surgery

Study Arms (2)

TENS - transcutaneous electrical nerve stimulation

EXPERIMENTAL

Device: TENS - transcutaneous electrical nerve stimulation

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

TENS - transcutaneous electrical nerve stimulation DEVICE

Pre-operative day 1 till postoperative day 14.

TENS - transcutaneous electrical nerve stimulation

Placebo OTHER

Pre-operative day 1 till postoperative day 14.

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (male/female) scheduled for Whipple procedure (pancreaticoduodenectomy)
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent must be available before enrolment in the trial

You may not qualify if:

• Patients \< 18 and \> 90 years of age
• Simultaneous participation in other clinical trials
• Pregnancy
• Current infection
• Hemophilia
• Psoriasis vulgaris
• Pacemaker, implanted cardioverter defibrillator, cardiac resynchronization therapy

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Allgemein,- Viszeral,- Transplantationschirurgie LKH Graz

Graz, Styria, 8036, Austria

Location

Related Publications (15)

• Tracey KJ. The inflammatory reflex. Nature. 2002 Dec 19-26;420(6917):853-9. doi: 10.1038/nature01321.

  PMID: 12490958 BACKGROUND

• Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009 Jun;9(6):418-28. doi: 10.1038/nri2566.

  PMID: 19461672 BACKGROUND

• Pavlov VA, Tracey KJ. The vagus nerve and the inflammatory reflex--linking immunity and metabolism. Nat Rev Endocrinol. 2012 Dec;8(12):743-54. doi: 10.1038/nrendo.2012.189.

  PMID: 23169440 BACKGROUND

• Levine YA, Koopman FA, Faltys M, Caravaca A, Bendele A, Zitnik R, Vervoordeldonk MJ, Tak PP. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One. 2014 Aug 11;9(8):e104530. doi: 10.1371/journal.pone.0104530. eCollection 2014.

  PMID: 25110981 BACKGROUND

• Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8284-9. doi: 10.1073/pnas.1605635113. Epub 2016 Jul 5.

  PMID: 27382171 BACKGROUND

• Nagle RT, Leiby BE, Lavu H, Rosato EL, Yeo CJ, Winter JM. Pneumonia is associated with a high risk of mortality after pancreaticoduodenectomy. Surgery. 2017 Apr;161(4):959-967. doi: 10.1016/j.surg.2016.09.028. Epub 2016 Nov 8.

  PMID: 27836210 BACKGROUND

• Patel SA, Gooderham NJ. IL6 Mediates Immune and Colorectal Cancer Cell Cross-talk via miR-21 and miR-29b. Mol Cancer Res. 2015 Nov;13(11):1502-8. doi: 10.1158/1541-7786.MCR-15-0147. Epub 2015 Jul 16.

  PMID: 26184038 BACKGROUND

• Song M, Kellum JA. Interleukin-6. Crit Care Med. 2005 Dec;33(12 Suppl):S463-5. doi: 10.1097/01.ccm.0000186784.62662.a1. No abstract available.

  PMID: 16340422 BACKGROUND

• Johnson DE, O'Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018 Apr;15(4):234-248. doi: 10.1038/nrclinonc.2018.8. Epub 2018 Feb 6.

  PMID: 29405201 BACKGROUND

• Koca YS, Bulbul M, Barut I. The Diagnostic Roles of Cytokines in Hepatobiliary Cancers. Biomed Res Int. 2017;2017:2979307. doi: 10.1155/2017/2979307. Epub 2017 Dec 19.

  PMID: 29410961 BACKGROUND

• Vainer N, Dehlendorff C, Johansen JS. Systematic literature review of IL-6 as a biomarker or treatment target in patients with gastric, bile duct, pancreatic and colorectal cancer. Oncotarget. 2018 Jul 3;9(51):29820-29841. doi: 10.18632/oncotarget.25661. eCollection 2018 Jul 3.

  PMID: 30038723 BACKGROUND

• Angele MK, Faist E. Clinical review: immunodepression in the surgical patient and increased susceptibility to infection. Crit Care. 2002 Aug;6(4):298-305. doi: 10.1186/cc1514. Epub 2002 May 24.

  PMID: 12225603 BACKGROUND

• Gurgen SG, Sayin O, Cetin F, Tuc Yucel A. Transcutaneous electrical nerve stimulation (TENS) accelerates cutaneous wound healing and inhibits pro-inflammatory cytokines. Inflammation. 2014 Jun;37(3):775-84. doi: 10.1007/s10753-013-9796-7.

  PMID: 24357416 BACKGROUND

• Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B.

  PMID: 12682500 BACKGROUND

• Trefz P, Rosner L, Hein D, Schubert JK, Miekisch W. Evaluation of needle trap micro-extraction and automatic alveolar sampling for point-of-care breath analysis. Anal Bioanal Chem. 2013 Apr;405(10):3105-15. doi: 10.1007/s00216-013-6781-9. Epub 2013 Feb 7.

  PMID: 23388692 BACKGROUND

MeSH Terms

Interventions

Transcutaneous Electric Nerve Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: February 24, 2023
• Study Start: February 15, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: February 24, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)