Feasibility and Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia
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.
Detailed description
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.
Arms & interventions
- DeviceSoterix tVNS 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.
- DeviceSoterix tVNS device (sham programmed)
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.
- BehavioralSleep Quality
Receive Pittsburgh Sleep Quality Index (PSQI); Insomnia Severity Index (ISI); Sleep diaries; Actigraphy via Fitbit Charge 5
- BehavioralNeurocognitive and mental health outcomes
Measured using CNS Vital Signs and DASS-21.
Outcome measures
Primary
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Eligibility criteria
Study locations (1)
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105