Nerve Stimulation During Esophagectomy

Feasibility of Splenic Nerve Stimulation During Esophagectomy

Esophagectomy is the cornerstone for treatment of esophageal cancer. However, it is associated with substantial morbidity and mortality. Studies suggest that systemic inflammation after surgery has a negative impact on surgical outcomes. Attenuation of an excessive inflammatory response within the perioperative period for high-risk surgical procedures may reduce morbidity and mortality. The inflammatory response may be important in the development of these complications and reduction of inflammatory cytokine may be associated with an improved outcome.

The current study will evaluate the feasibility and safety of neuromodulation during minimally invasive surgery for esophageal cancer (esophagectomy) to assess impact on the inflammatory response. During the esophagectomy, a stimulation lead will be placed on the exposed nerves, and energy applied to the lead to test whether the nerves can be activated. The study will also measure potential physiological responses to nerve activation.

Study Overview

• Status: Completed
• Conditions: Inflammatory Response
• Intervention / Treatment: Device: Stimulator device

Detailed Description

Active dampening of the inflammatory response may be an important therapeutic target to decrease complications and improve recovery following esophagectomy. The current study is intended to evaluate the feasibility and safety of stimulating the exposed nerves in esophagectomy patients.

During minimally invasive esophagectomy, a neurovascular bundle (NVB) is exposed or partially exposed as part of the obligatory lymph node dissection. At the point in the esophagectomy when the NVB is being isolated, a lead will be applied laparoscopically to the NVB and connected to an external pulse generator. An ultrasound transducer will be introduced to the abdomen and placed on the NVB to visualize splenic arterial blood flow. The NVB will be stimulated while physiologic responses are observed. Blood samples will be taken before, and at certain pre-defined time points after, stimulation and recovery. The lead and ultrasound transducer will be removed after completion of stimulation, and the esophagectomy surgery will continue. Surgeon experience applying and removing the cuff electrode will be documented, in addition to the responses to NVB stimulation. Post-operative safety will be followed through 7-days (or day of discharge if earlier).

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female of non-reproductive potential or male
• Undergoing minimally invasive esophagectomy
• Confirmed presence of splenic NVB loop via imaging prior to surgery
• Age equal or above 21 years at the screening visit
• Capable of giving signed informed consent (IC)
• Normal blood pressure, or hypertensive managed with medication such that they are deemed fit for surgery

Exclusion Criteria:

• Previous splenectomy
• Existing implantable device
• Active pancreatitis or history of severe pancreatitis with complications, hepatic or splenic disease
• Use of oral steroids 4 weeks prior to inclusion
• Current use immunosuppressive agents or biologicals. Previous use of biologicals is allowed, if a washout period of 2 months is applied
• Use of anticoagulants within 1 week of surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DEVICE_FEASIBILITY
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Nerve Stimulation; Participants will undergo brief NVB stimulation during the esophagectomy procedure.	Device: Stimulator device; The stimulator device will be used to electrically stimulate the NVB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility applying and removing the stimulation lead: Proportion of participants in whom the lead was successfully applied and removed	Proportion of participants in whom the lead was successfully applied and removed	1 day
Safety of placement, stimulation and removal of the lead: Incidence of adverse events	Incidence of adverse events	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak Systolic Velocity (PSV) blood flow change measured by doppler ultrasound	Before stimulation and during stimulation
End Diastolic Velocity (EDV) blood flow change measured by doppler ultrasound	Before stimulation and during stimulation
Velocity Time Integral (VTI) blood flow change measured by doppler ultrasound	Before stimulation and during stimulation

Other Outcome Measures

Outcome Measure	Time Frame
Heart Rate (HR) change	Before stimulation and during stimulation
Systolic Blood Pressure (SBP) change	Before stimulation and during stimulation
Diastolic Blood Pressure (DBP) change	Before stimulation and during stimulation
Mean Arterial Blood Pressure (MAP) change	Before stimulation and during stimulation
Hematology (white blood cell (WBC) counts)	Before stimulation to Day 1 post stimulation
Cytokine IL-6	Before stimulation to Day 1 post stimulation
Cytokine IL-8	Before stimulation to Day 1 post stimulation
Cytokine IL-10	Before stimulation to Day 1 post stimulation
Cytokine TNF	Before stimulation to Day 1 post stimulation
C-Reactive Protein level	At days 2 and 3 post stimulation

Collaborators and Investigators

• Sponsor: Galvani Bioelectronics
• Collaborators: NAMSA

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 28, 2019
• Primary Completion (ACTUAL): October 6, 2020
• Study Completion (ACTUAL): October 6, 2020

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (ACTUAL): November 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: GAL1018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No