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NCT Number: NCT07689981

The Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation in Individuals With Tiletamine Use Disorder

Participants diagnosed with tiletamine use disorder will be assigned to active or sham taVNS for 5 days. Clinical outcomes ( e.g., behavioral paradigms measures and clinical scales ) and physiological markers (e.g., EEG and ECG) will be evaluated at baseline, post-treatment, and 3-month follow-ups to determine therapeutic efficacy and mechanisms of action.

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Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

Tiletamine use disorder has emerged as a significant public health concern characterized by persistent psychological craving and high relapse rates. This randomized, double-blind, sham-controlled clinical trial aims to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) can reduce craving levels and improve other outcomes in individuals with tiletamine dependence. Multimodal assessments including electroencephalography (EEG), electrocardiography (ECG) , behavioral paradigms measures and clinical scales will be conducted before and after the treatment.

This study seeks to establish a non-invasive vagus nerve stimulation strategy for substance use disorders and explore the treatment mechanism.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-60 years ≥6 years of education[7.1] DSM-5 diagnosis of substance use disorder related to tiletamine Tiletamine use ≥6 months and ≥1 time/week Ability to provide informed consent Willingness to complete follow-up assessments

Exclusion criteria

  • Severe cognitive impairment History of epilepsy, brain injury, neurological disease or serious psychiatric disease Use of cognition-enhancing medications within 6 months Other psychoactive substance abuse within past 5 years (except nicotine) Metal implants in the head or severe skin sensitivity

Treatment and study plan

Transcutaneous Auricular Vagus Nerve Stimulation

Device

The stimulation duration is 40 minutes per session, administered four times daily for 5 consecutive days (20 sessions in total).

Sham stimulation

Device

Identical device appearance and parameters, with minimal sensory stimulation and no vagal activation. The treatment schedule is identical to that of the active group.

Primary outcomes

  1. Change of depressive symptoms

    Time frame: Baseline, immediately after the intervention,one month after the intervention

    The PHQ-9, fully known as the Patient Health Questionnaire-9, is a self-report assessment tool developed based on the diagnostic criteria in the American Diagnostic and Statistical Manual of Mental Disorders for screening and evaluating the severity of depression. The scale consists of nine items corresponding to the core symptoms of depression. Respondents rate the frequency of symptoms experienced over the past two weeks on a scale of 0 to 3. The total score ranges from 0 to 27, with higher scores indicating potentially more severe depressive symptoms.

Secondary outcomes

  1. Change of stress symptoms

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    PSS stands for the Perceived Stress Scale. It is used to assess an individual's subjective perceptions of stress and the frequency of stress-related thoughts and feelings over the past month. The scale consists of 14 items, with derived 10-item and 4-item versions also available, and uses a five-point scoring system from 0 to 4, ranging from "never" to "very often". It provides a quick measure of an individual's perceived stress level. The total score ranges from 0 to 56, corresponding to three stress levels: normal (0-28), elevated (29-42), and high (43-56). The scale helps identify stress status and provides guidance for adjusting support resources.

  2. Change of the sleep quality

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    Sleep quality will be measured by the Pittsburgh Sleep Quality Index (PSQI). The total score of PSQI ranges from 0 to 21, in which higher scores mean poorer sleep quality.

  3. Change of the anxiety symptoms

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The GAD-7 is a self-report scale for assessing anxiety symptoms. It consists of seven items assessing: 1. nervousness or anxiety; 2. uncontrollable worry; 3. excessive worry; 4. difficulty relaxing; 5. restlessness; 6. irritability; and 7. a sense of imp

  4. Change of the risky decision-making performance

    Time frame: Baseline, immediately after the intervention

    Risky decision-making performance will be assessed using the Balloon Analogue Risk Task (BART). Higher average pumps in the BART indicate greater risk-taking propensity. Electroencephalography (EEG) will be used to measure neural electrical signals, where increases in relevant electrophysiological indicators may reflect heightened individual sensitivity to negative feedback. Higher frequency of continued dice rolls indicates greater risk propensity. Neural activity features related to the task will be analyzed, with specific patterns associated with risk evaluation and reward processing.

  5. Changes in Negative Reinforcement Learning Behaviour

    Time frame: Baseline, immediately after the intervention,

    A negative reinforcement learning paradigm was used to assess avoidance-reversal learning behaviour. Behavioural response bias and learning rate were used to characterise negative reinforcement behavioural traits and negative reinforcement learning ability. EEG was recorded simultaneously, and changes in relevant electrophysiological indicators may serve as electrophysiological markers of changes in negative reinforcement learning behaviour.

  6. The change of alcohol craving

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    Alcohol craving will be measured by the alcohol craving Visual Analog Scale (VAS). The total score of VAS ranged from 0 to 10, in which higher scores mean a higher level of alcohol craving.

  7. The change of alcohol use

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The AUDIT (the Alcohol Use Disorders Identification Test) consists of 10 items covering drinking frequency, alcohol consumption, alcohol dependence-related symptoms, and adverse consequences caused by alcohol use. Respondents complete the questionnaire based on their recent drinking behaviour, with each item scored according to different response levels. The total score ranges from 0 to 40. Higher scores indicate a higher risk of alcohol-related problems, and the scale can be used to identify hazardous drinking, harmful drinking, and potential risk of alcohol dependence.

  8. The changes of Resilience

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The China version of the Connor-Davidson Resilience Scale (CD-RISC) consists of 25 items and includes three dimensions: tenacity (13 items), strength (8 items), and optimism (4 items). The scale uses a 5-point Likert scoring method, with scores from 0 to 4 representing "not true at all", "rarely true", "sometimes true", "often true", and "true nearly all the time", respectively. The total score ranges from 0 to 100, with higher scores indicating greater psychological resilience. The internal consistency coefficient of the Chinese version is 0.91.

  9. The condition of childhood experiences

    Time frame: Baseline

    Adverse Childhood Experiences (ACEs) includes 25 clinical items and 3 validity items. The scale uses a 5-point scoring system, ranging from "never true" to "very often true". Each subscale score ranges from 5 to 25 and is calculated by summing the scores of the items within that subscale. The total CTQ score is calculated by summing the subscale scores. Higher scores indicate more severe reported childhood maltreatment.

  10. The change of nicotine dependence

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The FTND is a self-report scale used to assess the severity of nicotine dependence among smokers. The scale usually consists of six items. The total score ranges from 0 to 10, with higher scores indicating more severe nicotine dependence. It can be used to assess the level of smoking addiction and support the development of smoking cessation interventions.

  11. Change of the self-control ability

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    Self-control ability will be measured using the Self-Control Scale (SCS). Higher scores of SCS indicate better self-regulation and impulse control.

  12. The changes of impulsive behavior

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    UPPS-P Impulsive Behavior Scale (UPPS-P) includes 59 items rated on a 4-point Likert scale. Respondents indicate their agreement or disagreement with statements using a 4-point scale (1 = Agree Strongly, 4 = Disagree Strongly). Scoring involves calculating a mean score for each of the five subscales (scaled 1-4) and a total impulsivity score.

  13. The changes of morningness-eveningness

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The Chinese version of the 5-item Morningness-Eveningness Questionnaire (rMEQ-5). The Chinese version of the MEQ-5 consists of five items selected from the Chinese version of the MEQ-19, namely items 1, 7, 10, 18, and 19.

  14. The change of impulsiveness

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The Barratt Impulsiveness Scale (BIS) consists of 30 items. Each item is rated according to the frequency of occurrence using a 4-point scoring method: rarely/never = 1, occasionally = 2, often = 3, and almost always/always = 4.

  15. The change of somatic symptom

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The Somatic Symptom Scale (SSS) consists of 20 items and is a self-report scale using a 4-point rating system (Table 1). A total raw score above 40 is considered positive.

  16. The change of behavioral inhibition/activation

    Time frame: Baseline, immediately after the intervention, one month after the intervention,

    The Behavioral Inhibition/Activation System Scale (BIS/BAS Scale) uses a 4-point scoring system, where 1 indicates "strongly agree" and 4 indicates "strongly disagree". Higher scores indicate greater activation of the behavioral inhibition system and behavioral activation system.

Study contacts

Contact information is provided by the study sponsor or research team.

Jiang Du, M.D, Ph.D

CONTACT

[email protected]

+8618017311220

Sponsors and collaborators

Lead sponsor

Shanghai Mental Health Center

Other

Registry information

Official study title

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Patients With Tiletamine Use Disorder: A Randomized Double-Blind Sham-Controlled Trial

Acronym: taVNS-Tiletami

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Jul 8, 2026
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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