Study of the Effects of Transcutaneous Vagus Nerve Stimulation on Cancer Patients

Study of the Effects of Transcutaneous Vagus Nerve Stimulation on Cancer Patients' Fatigue, Quality of Life and Lymphopenia After Radiotherapy or Chemotherapy

Patients diagnosed with nasopharyngeal cancer, esophageal cancer, lung cancer, cervical cancer, rectal cancer, or breast cancer who received radical radiotherapy/neoadjuvant/assisted radiotherapy were recruited and the transcutaneous vagal nerve stimulation (tVNS) was applied. The aim of of study is : 1) to study whether tVNS could improve the patient's fatigue, quality of life under radiotherapy or chemotherapy; 2) to investigate the effects of transcutaneous VNS on the levels of patients' lymphocyte subsets and proinflammatory cytokines.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Esophageal Cancer; Chemotherapy Effect; Cancer, Therapy-Related
• Intervention / Treatment: Device: Transcutaneous vagus nerve stimulation

Detailed Description

A prospective, randomized, double-blind, parallel controlled trial was conducted. This trail is to recruit 130 patients diagnosed with above specific types of cancer undergoing radical radiotherapy/neoadjuvant/adjuvant radiotherapy. Participants were randomly assigned to the two groups with 65 in each group. According to treatment mode (radical radiotherapy vs neoadjuvant or adjuvant radiotherapy) and staging (stage I-II vs stage III), the participants were randomly divided into two groups: 1) sham tVNS with conventional radiotherapy and chemotherapy (control group); 2) tVNS with conventional radiotherapy and chemotherapy (intervention group). tVNS was conducted at every radiotherapy day for at least 4 weeks. tVNS stimulation method: in the control group, the ear clip electrodes were clamped at the earlobe; in the intervention group, the ear clip electrode was clamped at the tragus. Stimulation duration would last for 30 minutes, and the stimulation intensity was adjusted to the minimum value of pain threshold. The Chinese version of the Concise Fatigue Scale (BFI-C), the European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30), Pittsburgh sleep quality index (PSQI) and Hospital Anxiety and Depression Scale (HADS) assessment, lymphocyte subpopulations,level of proinflammatory factors, blood routine testing and electrocardiogram testing were performed within 2 weeks before treatment (baseline), 4 weeks after intervention, at the end of chemoradiation, 1 month and 4 month after the end of chemoradiation; weekly blood routine testing during intervention under radiotherapy and chemotherapy; the incidence of side effects and sleep quality score were evaluated at baseline, 2 weeks and 4 weeks after the intervention, at the end of radiotherapy and chemotherapy, and 1 month after the end of radiotherapy. The number of recruited participants met the statistical requirements.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Deng, Phd; Phone Number: 18811796557 18811796557; Email: [email protected]

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Recruiting
      • Xidian University
      • Contact: Wei Qin, Doctor; Phone Number: +8615691826100; Email: [email protected]
      • Principal Investigator: Li-Na Zhao, Doctor
      • Principal Investigator: Wei Qin, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants diagnosed with nasopharyngeal cancer, esophageal cancer, lung cancer, or cervical cancer, suitable for radical radiotherapy or chemotherapy;
2. Participants diagnosed with rectal cancer, suitable for neoadjuvant radiotherapy or chemotherapy before surgery;
3. Participants diagnosed with breast cancer, suitable for adjuvant radiotherapy after surgery;
4. Eastern Cooperative Oncology Group (ECOG) physical condition score: 0~1 point.

Exclusion Criteria:

1. Participants with organic brain lesions (cerebral hemorrhage, large-area cerebral infarction, encephalitis, epilepsy, etc.);
2. Participants with peptic ulcer, arrhythmia, or cardiac corrected QT interval> 450ms;
3. Participants who have slow breathing (less than 10 breaths per minute);
4. Participants who are or have been diagnosed with other major diseases (coronary heart disease, pulmonary heart disease, etc.);
5. Participants who are currently or have been diagnosed with mental disorders other than major depressive disorder;
6. Participants who are or have participated in vagus nerve or transcranial electrical stimulation treatment for less than 3 months;
7. Participants who are not suitable for vagus nerve stimulation treatment;
8. Participants who refuse to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham tVNS; The participants under conventional radiochemotherapy were applied with sham tVNS at the earlobe for 30min and the current intensity was set according to the minimum value of pain threshold. The intervention would last until to the end of conventional radiochemotherapy.	Device: Transcutaneous vagus nerve stimulation; the transcutaneous vagus nerve stimulation was conducted by ear clip with cathode and anode placed at the tragus for 30 min.
Active Comparator: tVNS; The participants under conventional radiochemotherapy were applied with transcutaneous vagus nerve stimulation at the tragus for 30min and the current intensity was set according to the minimum value of pain threshold. The intervention would last until to the end of conventional radiochemotherapy.	Device: Transcutaneous vagus nerve stimulation; the transcutaneous vagus nerve stimulation was conducted by ear clip with cathode and anode placed at the tragus for 30 min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the score of fatigue	the score of fatigue in two groups will be evaluated by BFI-C and will be compared	4 weeks after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the change of the fatigue score at baseline and after intervention	compare the change of fatigue levels between two groups	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy
the life quality of participants	the life quality will be evaluated by QLQ-C30 (V3.0) of Chinese version	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy
the depression level of participants	the depression level will be evaluated by HADS	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy
Lymphocytes and their subpopulations in blood circulation	the absolute value of lymphocytes ,the ratio of its subpopulations and the decline ratio will be detected and analyzed.	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy
proinflammatory factors in blood circulation	the levels of proinflammatory factors, such as tumor necrosis factor-α (TNF-α) , interleukin-6 (IL-6) and C-response protein (CRP) in serum were detected.	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy
the level of sleep quality	the level of sleep quality will be evaluated by PSIQ	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy
Lymphocyte nadirs	the minimum value of lymphocytes and its difference to that at baseline	baseline(during 2 weeks before intervention), 4 weeks after intervention, 1 month and 4 month after the therapy

Collaborators and Investigators

• Sponsor: Xidian University
• Collaborators: The First Affiliated Hospital of the Fourth Military Medical University
• Investigators: Principal Investigator: Li-Na Zhao, Doctor, The First Affiliated Hospital of the Fourth Military Medical University; Principal Investigator: Wei Qin, Doctor, Xidian University

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2020
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): December 30, 2021

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Cancer; Vagus nerve stimulation; Lymphocytes; Life quality
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms, Second Primary
• Other Study ID Numbers: 20200110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: the data will be available by the publication of articles
• IPD Sharing Time Frame: The information will be available by the publication of articles
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

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