Efficacy of TaVNS Versus Sham Stimulation in Reduing Depressive Symptoms in Patients with Epilepsy: a Multi-center, Double-blinded, Randomized, 20-week, Parallel-arm, Superiority Study (TIDES)

The purpose of this study is to compare the efficacy of taVNS versus sham stimulation in reduing depressive symptoms in patients with epilepsy.

Study Overview

• Status: Active, not recruiting
• Conditions: Depressive Symptoms in Patients with Epilepsy
• Intervention / Treatment: Device: Intervention; Device: Sham Comparator

• Study Type: Interventional
• Enrollment (Estimated): 158
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital, School of Medicine, Zhejiang University
    • Jiaxing, Zhejiang, China, 314000
      • The First People's Hospital of Jiaxing
    • Jinhua, Zhejiang, China, 321000
      • Jinhua Second Hospital
    • Ningbo, Zhejiang, China, 315040
      • Ningbo Medical Center Li Huili Hospital
    • Yiwu, Zhejiang, China, 322000
      • The Fourth Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults age ≥18
• Confirmed diagnosis of epilepsy (based on 2014 definition by ILAE)
• Having comorbidity with mild-moderate depression (confirmed diagnosis by a psychiatrist)
• Willing and able to provide informed conset

Exclusion Criteria:

• Those experiencing status epilepticus or frequent seizures requiring emergency medication within the year prior to recruitment
• Those with severe depression or anxiety who are in urgent need of psychiatric care
• Those who are imminently suicidal or unable to keep themselves safe
• Those experiencing severe cognitive difficulties with day-to-day memory, attention, and ability to learn basic information
• Those having a pacemaker, a invasive vagus nerve stimulator, or a metal implant
• The pinna is not suitable for earplugs
• Pregnancy

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
Experimental: "xinlepai","taVNS" 25Hz; The "xinlepai", a transcutaneous auricular vagus nerve stimulator (taVNS), was used with a stimulation frequency of 25Hz, combined with conventional treatment. Use 3 times daily for 30 minutes each time.	Device: Intervention; taVNS 25Hz+routine treatment, three times daily, 30 mins
Sham Comparator: "xinlepai","taVNS" 1Hz; The "xinlepai", a transcutaneous auricular vagus nerve stimulator (taVNS), was used with a stimulation frequency of 1Hz, combined with conventional treatment. Use 3 times daily for 30 minutes each time.	Device: Sham Comparator; taVNS 1Hz+routine treatment, three times daily, 30 mins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression response proportion	depression response proportion=(number of responders/total number of group patients)*100%, depression response defined as ≥50% reduction in HAMD-17 scores at 20th week	at 20th week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression remission proportion	depression remission proportion=(number of remission patients/total number of group patients)*100%, depression remission defined as HAMD-17 scores ≤ 7	at 20th week
Anxiety	Changes in the 14-item Hamilton Anxiety Scale (HAMA-14) score from baseline.The total score of the HAMA-14 ranges from 0 to 56, with the higher the score, the more serious the anxiety.	at 20th week
Seizure frequency	change from baseline in seizure frequency (times per week)	at 20th week
Seizure severity	change from baseline in Liverpool Seizure Severity Scale (LSSS) scores.The total score of the LSSS ranges from 0 to 11 points, and the higher the score, the higher the severity of seizures	at 20th week
Sleep quality	change from baseline in Pittsburgh Sleep Quality Index (PSQI) scores.The total score of PSQI ranges from 0 to 21, with the higher the score, the worse the sleep quality.	at 20th week
Suicidality	change from baseline in the Mini-International Neuropsychiatric Interview (MINI) Suicide Risk Module scores.The MINI Suicide Risk Module has an overall score ranging from 0 to 33, with higher scores associated with higher suicide risk.	at 20th week
Quality of life	change from baseline in quality of life in epilepsy inventory-31 scale, which has a total of 31 items divided into 7 aspects and 1 overall entry, the higher the score, the higher the quality of life.	at 20th week
Adverse events	patient-reported adverse events	at 4th 、8th、12th、16th、20th 、22th week

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Ningbo Medical Center Lihuili Hospital; First Affiliated Hospital of Zhejiang University; The Fourth Affiliated Hospital of Zhejiang University School of Medicine; Jinhua Second Hospital
• Investigators: Principal Investigator: yi guo, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 17, 2024
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: depression; epilepsy; transcutaneous auricular vagus nerve stimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Behavioral Symptoms; Depression; Epilepsy
• Other Study ID Numbers: 2023-0182

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No