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NCT Number: NCT07191119

Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia

This pilot study will assess the usefulness and potential effectiveness of using transcutaneous auricular vagus nerve stimulation (tVNS) for treating insomnia in adult survivors of childhood acute lymphoblastic leukemia (ALL). Participants will be randomized to receive either active (verum) or inactive (sham) nightly stimulation using a non-invasive earbud device over two time periods: 2 weeks and 8 weeks. The study will assess adherence to the intervention and estimate its effects on sleep quality, stress, and neurocognitive function.

Primary Objective:

Aim 1: To determine a) short-term and b) long-term feasibility of tVNS in terms of participation in ALL Survivors with moderate to severe insomnia.

Aim 2: To estimate the effect size of tVNS on sleep quality, stress, and neurocognitive outcomes in ALL survivors with insomnia.

Exploratory Objectives

Aim 1: To investigate the onset of tVNS effect via actigraphy measures over the intervention epoch.

Aim 2: To estimate the effect size of genetic variants on sleep quality within verum tVNS.

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Key information

Conditions

Survivor of Childhood Cancer Acute Lymphoblastic Leukemia (ALL) Dyssomnias Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Insomnia Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Mental Disorders Neoplasms Neoplasms by Histologic Type Nervous System Diseases Precursor Cell Lymphoblastic Leukemia-Lymphoma Sleep Disorders, Intrinsic Sleep Initiation and Maintenance Disorders Sleep Wake Disorders

Age range

20 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location status: Recruiting

Location contact

Justin E Tanner, PhD

CONTACT

[email protected]

888-226-4343

About this study

Approximately 40 adult survivors of childhood ALL enrolled in the SJLIFE cohort will be recruited. Eligible participants must have moderate to severe insomnia (ISI ≥8). The intervention involves nightly use of a tVNS device for 20 minutes before sleep. Participants will be randomized to receive either active or sham stimulation. Feasibility will be assessed based on adherence rates, and efficacy will be estimated using subjective (PSQI, ISI) and objective (actigraphy, CNS Vital Signs) measures. Exploratory analyses will examine the onset of tVNS effects and the influence of genetic variants (BDNF rs6265, COMT rs4680) on treatment response.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Survivor of Acute Lymphoblastic Leukemia (ALL)
  • Enrolled on SJLIFE
  • Participant was less than 21 years of age at time of diagnosis.
  • Age 20-50 years at the time of enrollment
  • Insomnia Severity Index >=8 (Proxy >=8) confirmed prior to enrollment
  • Access to home Wi-Fi and Smartphone
  • Participant is able to speak and understand the English language
  • Participant is able and willing to give consent

Exclusion criteria

  • Unable to understand the details and requirements of the study (at the discretion of the PI)
  • Female participants who are pregnant or planning to become pregnant
  • Presence of implanted electrical medical devices (i.e. pacemaker)
  • Currently taking medication intended to treat neurocognitive impairment (i.e. stimulants) or medications prescribed for seizure management
  • History of skin irritation or other issues during stimulation of inner ear
  • Currently utilizing a technological intervention for a sleep disorder (e.g. CPAP)
  • Medications and behavioral practices (white noise, night-time yoga, etc) are acceptable as long as the insomnia is persistent.
  • History of a contraindicated health condition including:
  • Syncope (CTCAE >2)
  • Cardiac dysrhythmia (CTCAE >2)
  • Vascular Disease (CTCAE >2)
  • Coronary Artery Disease (CTCAE >2)
  • Active contraindicated heath condition including:
  • Cranial Nerve Disorder (CTCAE >2)
  • Cardiac tachycardia (CTCAE >2)
  • Neuropathy (Cranial Nerves) (CTCAE >2)
  • Neuralgia (Cranial Nerves) (CTCAE >2)
  • Overt Cerebrovascular Accident (CTCAE >2)
  • Seizures (Any in most recent 1 year
  • Currently enrolled or participating in any other neurostimulation or neuromodulation ancillary research studies

Treatment and study plan

Soterix tVNS device

Device

Active transcutaneous auricular vagus nerve stimulation (tVNS) using the Soterix device.

Stimulation is delivered nightly for 20 minutes at 80% of the participant's discomfort threshold.

Other names: tVNS

Soterix tVNS device (sham programmed)

Device

The sham stimulation used the Soterix device, but without active electrical stimulation. The procedure mimics the verum condition in duration and setup. Inactive stimulation is delivered nightly for 20 minutes at 80% of the participant's discomfort threshold.

Sleep Quality

Behavioral

Receive Pittsburgh Sleep Quality Index (PSQI); Insomnia Severity Index (ISI); Sleep diaries; Actigraphy via Fitbit Charge 5

Neurocognitive and mental health outcomes

Behavioral

Measured using CNS Vital Signs and DASS-21.

Primary outcomes

  1. Mean Change in Subjective Sleep Quality

    Time frame: Baseline, 2-weeks, 8-weeks

    Pittsburgh Sleep Quality Index (PSQI, 0-57 points). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  2. Mean change in clinical insomnia score

    Time frame: Baseline, 2-weeks, 8-weeks

    Insomnia Severity Index (ISI, 0-28 points). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  3. Occurrence of side effects

    Time frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7

    Patient Report of Incidence of Side Effects (PRISE). Descriptive statistics of the change between baseline and 2 and 8 weeks will be reported.

  4. Adherence to intervention

    Time frame: 2-weeks, 8-weeks

    Number of tVNS sessions performed. Descriptive statistics of adherence at 2 weeks and 8 weeks will be reported.

  5. Mean change in Processing Speed (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Symbol Digit Coding Test as the difference between correct responses and errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  6. Mean change in Executive Function (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Shifting Attention Task as the difference between correct responses and errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  7. Mean change in Simple Attention (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Continuous Performance Test as the difference between correct responses and commission errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  8. Mean change in Reaction Time (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Stroop Test as the average of reaction times in the complex and default trials. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  9. Mean change in Sustained Attention (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Four-Part Continuous Performance Test as the difference between correct responses and incorrect responses in Part 2, 3, and 4. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  10. Mean change in Working Memory (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Four-Part Continuous Performance Test as the difference between correct responses and incorrect responses in Part 4 only. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  11. Mean change in Complex Attention (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Evaluated with the Stroop Test (ST), Shifting Attention Test (SAT), and Continuous Performance Test (CPT) as the sum of ST commission errors, SAT errors, CPT commission errors, and CPT omission errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  12. Mean change in Cognitive Flexibility (age adjusted z-score)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Evaluated with the Stroop Test (ST) and Shifting Attention Test (SAT) as the difference between SAT correct responses and the sum of the SAT errors and ST commission errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  13. Mean change in Depression, Anxiety, and Stress (scales)

    Time frame: Baseline, 2-Weeks, 8-weeks

    Evaluated with Depression Anxiety Stress Scale Short Form (DASS SF-21). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported. DASS SF-21 are reported as population z-scores and categorized into five severity ranges: normal, mild, moderately severe, and extremely severe. The severity levels, higher percentiles being more severe, are determined by z-scores from the DASS manual.

  14. Mean Change in Heart Rate Variability (ms)

    Time frame: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks

    Root Mean Square Successive Difference (RMSSD) of heart rate variability. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  15. Mean Change in Sleep Onset Latency (minutes)

    Time frame: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks

    Sleep Onset Latency (time in bed before sleep). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

  16. Mean Change in Waking Events (count)

    Time frame: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks

    Number of Awakenings. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.

Study contacts

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

Justin E Tanner, PhD

CONTACT

[email protected]

888-226-4343

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Registry information

Official study title

Feasibility and Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia

Important dates

Study start
2026
Primary completion
2027
Study completion
2029
First posted
Sep 24, 2025
Registry last updated
Jul 28, 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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