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NCT03959111

Auricular Vagus Nerve Stimulation for Chronic Pain

Completed NA Results posted Last updated 11 March 2026
What this trial tests

NA trial testing Stimulation at Location 1 in Low Back Pain in 70 participants. Completed in 30 April 2024.

Timeline
17 October 2019
Primary endpoint
30 April 2024
30 April 2024

Quick facts

Lead sponsorMassachusetts General Hospital
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment70
Start date17 October 2019
Primary completion30 April 2024
Estimated completion30 April 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Massachusetts General Hospital

Who can join

Adults 18 to 65, any sex, with Low Back Pain. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Low Back Pain Intensity Primary · 1 month

This is a uni-dimensional measure of chronic low back pain intensity. It uses an 11-point numeric scale (0 indicate no pain, and 10 indicates max level of pain that can be imagined). We will use it to measure the patient's average pain intensity in the past week, which will be measured at the beginning and end of the study.

GroupValue95% CI
Ear Stimulation (Area With VN)1.24± 1.73
Ear Stimulation (Area Without VN)1.73± 1.23
Roland-Morris Disability Questionnaire Score Secondary · 1 months

The Roland-Morris Disability Questionnaire (RMDQ) is a widely used self-reported measure of physical disability specifically designed for individuals with low back pain. The questionnaire assesses the impact of back pain on daily activities. The total score ranges from 0 to 24, where: 0 indicates no disability, 24 indicates severe disability.

GroupValue95% CI
Ear Stimulation (Area With VN)2.3± 4.1
Ear Stimulation (Area Without VN)1.7± 3.9
Patient-Reported Outcomes Measurement Information System (PROMIS) Scores Secondary · baseline and post-treatment

The PROMIS, funded by the NIH, is a system containing reliable, flexible, precise, and responsive assessment tools that have been widely validated in numerous samples. 29 items covering seven domains and one additional question about pain intensity. Here we focus on Pain Interference (4 items, raw score range 4-20, T-score range roughly 41-76, mean and SD in chronic pain patients is 67.1 and 5.79. The 67.1indicates the population mean in chronic pain patients with a standard deviation of 5.79 based on publication PMCID: PMC8412832). Higher T-scores = more pain interference. We compared pre- an

GroupValue95% CI
Ear Stimulation (Area With VN)3.5± 6.0
Ear Stimulation (Area Without VN)4.4± 4.9
The Pennebaker Inventory of Limbic Languidness Secondary · Baseline

The Pennebaker Inventory of Limbic Languidness (PILL) is a self-report questionnaire assessing the frequency of common physical symptoms. Participants rate how often they have experienced each symptom over a specified retrospective period using a 5-point Likert scale. The PILL includes a broad range of symptoms, including pain-related items (e.g., headache, back pain, sore muscles). The PILL was administered at baseline only to characterize baseline symptom sensitivity/awareness and to reduce participant burden. Total scores are computed as the sum of 53 items rated from 1-5 (total score range

GroupValue95% CI
Ear Stimulation (Area With VN)103.2± 32.1
Ear Stimulation (Area Without VN)98.9± 28.0
Resting State Functional Connectivity Changes of the PAG Secondary · 1 month

Resting state functional connectivity refers to the statistical relationship between the time-series activity of different brain regions as measured by functional MRI (fMRI). Functional connectivity changes of the periaqueductal gray (PAG) at rest refer to alterations in the neural communication between the PAG and other brain regions when a subject is not actively engaged in a task. The PAG, located in the midbrain, plays a critical role in pain modulation, defensive behavior, and autonomic regulation.

GroupValue95% CI
Ear Stimulation (Area With VN)0.1± 0.1
Ear Stimulation (Area Without VN)-0.1± 0.1
Resting State Functional Connectivity of the Medial and Lateral Hypothalamus Secondary · 1 month

Resting state functional connectivity refers to the statistical relationship between the time-series activity of different brain regions as measured by functional MRI (fMRI). Functional connectivity changes of the medial and lateral hypothalamus at rest refer to alterations in the neural communication between the two regions and other brain regions when a subject is not actively engaged in a task.

GroupValue95% CI
Ear Stimulation (Area With VN)0.1± 0.1
Ear Stimulation (Area Without VN)-0.03± 0.1
CBF as Measured by ASL Secondary · 1 month

Changes in cerebral blood flow were evaluated by comparing pre-to-post change between the real and sham groups. Statistically significant clusters identified in this comparison are reported in the Results Data Tables, including a cluster located in the precentral gyrus.

GroupValue95% CI
Ear Stimulation (Location 1)-8.4± 15.87
Ear Stimulation (Location 2)2.87± 14.46
Inflammation Biomarkers Secondary · 1 month

Changes in inflammatory biomarker levels of PD1 between baseline and week 4

GroupValue95% CI
Ear Stimulation (Area With VN).01± 44.99
Ear Stimulation (Area Without VN)4.76± 41.33

Adverse events — posted to ClinicalTrials.gov

Time frame: Over the 4-week intervention. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ear Stimulation (Area With VN)
Serious: 0/36 (0%)
Deaths: 0/36
Ear Stimulation (Area Without VN)
Serious: 0/34 (0%)
Deaths: 0/34
Other adverse events (5 terms — click to expand)

ReactionSystemEar Stimulation (Area With…Ear Stimulation (Area With…
lightheadedNervous system disorders
HeadacheNervous system disorders
appendicitisGastrointestinal disorders
Tingling in armsNervous system disorders
NauseaGastrointestinal disorders

Data from ClinicalTrials.gov NCT03959111 adverse events section.

Sponsor's own description

This proposal aims to investigate the treatment effect and underlying mechanism of transcutaneous acupuncture stimulation on chronic low back pain. We believe that this study, if successful, will provide new treatment options for chronic low back pain, reduce the use of opioid analgesics in chronic pain management, and enhance our understanding of the underlying mechanism of nerve stimulation treatment, as well as the pathophysiology and development of chronic pain.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Transcutaneous auricular nerve stimulation modulates the functional connectivity of the descending pain modulation system and reward network in patients with chronic low back pain.
    Li T, Wu Y, Li Y, Hodges SA, et al · · 2025 · cited 3× · PMID 40461351 · DOI 10.1016/j.neurot.2025.e00611
  2. Both Transcutaneous Auricular Vagus Nerve Stimulation and Great Auricular Nerve Stimulation Modulate Functional and Structural Connectivity of Brainstem Nuclei in Chronic Low Back Pain.
    Li Y, Li T, Yan K, Wu J, et al · · 2026 · PMID 41091086 · DOI 10.1016/j.neurom.2025.08.415

Verify or expand the search:

Other recruiting trials for Low Back Pain

Currently open trials in the same condition.

Other Massachusetts General Hospital trials

Trials by the same sponsor.

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