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

DEVICE

Soterix 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.

DEVICE

Soterix 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.

BEHAVIORAL

Sleep Quality

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

BEHAVIORAL

Neurocognitive and mental health outcomes

Measured using CNS Vital Signs and DASS-21.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.