Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia
Feasibility and Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia
2 other identifiers
interventional
40
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Mar 2026
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2025
CompletedFirst Posted
Study publicly available on registry
September 24, 2025
CompletedStudy Start
First participant enrolled
March 31, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
April 24, 2026
April 1, 2026
1.7 years
August 26, 2025
April 23, 2026
Conditions
Outcome Measures
Primary Outcomes (16)
Mean Change in Subjective Sleep Quality
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.
Baseline, 2-weeks, 8-weeks
Mean change in clinical insomnia score
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.
Baseline, 2-weeks, 8-weeks
Occurrence of side effects
Patient Report of Incidence of Side Effects (PRISE). Descriptive statistics of the change between baseline and 2 and 8 weeks will be reported.
Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7
Adherence to intervention
Number of tVNS sessions performed. Descriptive statistics of adherence at 2 weeks and 8 weeks will be reported.
2-weeks, 8-weeks
Mean change in Processing Speed (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Executive Function (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Simple Attention (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Reaction Time (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Sustained Attention (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Working Memory (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Complex Attention (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Cognitive Flexibility (age adjusted z-score)
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.
Baseline, 2-Weeks, 8-weeks
Mean change in Depression, Anxiety, and Stress (scales)
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.
Baseline, 2-Weeks, 8-weeks
Mean Change in Heart Rate Variability (ms)
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.
Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Mean Change in Sleep Onset Latency (minutes)
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.
Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Mean Change in Waking Events (count)
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.
Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Study Arms (2)
Verum tVNS (Active Treatment)
EXPERIMENTALParticipants randomized to receive 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.
Sham tVNS (Placebo Comparator)
SHAM COMPARATORParticipants randomized to receive sham stimulation using the same Soterix device, but with no active electrical stimulation. The procedure mimics the verum condition in duration and setup.
Interventions
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.
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.
Receive Pittsburgh Sleep Quality Index (PSQI); Insomnia Severity Index (ISI); Sleep diaries; Actigraphy via Fitbit Charge 5
Measured using CNS Vital Signs and DASS-21.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- Neuropathy (Cranial Nerves) (CTCAE \>2)
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Justin E Tanner, PhD
St. Jude Children's Research Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- DEVICE FEASIBILITY
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 26, 2025
First Posted
September 24, 2025
Study Start
March 31, 2026
Primary Completion (Estimated)
December 1, 2027
Study Completion (Estimated)
December 1, 2029
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available at the time of article publication.
- Access Criteria
- Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.