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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Mean Change in Subjective Sleep Quality [Time frame: Baseline, 2-weeks, 8-weeks]
• Mean change in clinical insomnia score [Time frame: Baseline, 2-weeks, 8-weeks]
• Occurrence of side effects [Time frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7]
• Adherence to intervention [Time frame: 2-weeks, 8-weeks]
• Mean change in Processing Speed (age adjusted z-score) [Time frame: Baseline, 2-Weeks, 8-weeks]
• Mean change in Executive Function (age adjusted z-score) [Time frame: Baseline, 2-Weeks, 8-weeks]
• Mean change in Simple Attention (age adjusted z-score) [Time frame: Baseline, 2-Weeks, 8-weeks]
• Mean change in Reaction Time (age adjusted z-score) [Time frame: Baseline, 2-Weeks, 8-weeks]
• Mean change in Sustained Attention (age adjusted z-score) [Time frame: Baseline, 2-Weeks, 8-weeks]
• Mean change in Working Memory (age adjusted z-score) [Time frame: Baseline, 2-Weeks, 8-weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Device feasibility

Study locations

United States · 1 center

• St. Jude Children's Research Hospital — Memphis

Identifiers

NCT: NCT07191119 · FANSI · NCI-2025-08555

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗