Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Aromatase Inhibitor-induced Arthralgia (AIA) (AROVAGUE)

May 20, 2026 updated by: Institut Cancerologie de l'Ouest

Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Aromatase Inhibitor-induced Arthralgia (AIA): a Phase 2, Randomized, Monocentric, taVNS Versus Sham, Double Blind

Breast cancer (BCa) is the most common cancer in women. The majority of BCa are hormone receptor positive and substantial benefits have been demonstrated for adjuvant endocrine therapies in reducing recurrence and extending survival in women.

Aromatase inhibitors (AI) are commonly prescribed for women diagnosed with hormone receptor positive BCa. In parallel with this improvement in survival, women may experience a frequent adverse effect from AI therapy with arthralgia, or joint pain and stiffness. AI-induced arthralgia (AIA) is experienced by about 50 % of recipients.

The main AIA symptoms are joint pain and stiffness, mainly in the hands, wrists, and knees, symmetrically.

Although AIA can occur at any time after initiating AI, the median time to onset is approximately 6 weeks with peak symptoms at 6 months.

Additionally, AIA impairs quality of life (QoL) and pain severity is associated with premature discontinuation and non-adherence to AI therapy which in turn is significantly associated with increased mortality in BCa patients.

Declining levels of oestrogen induced by AI results in increased production of proinflammatory cytokines hitting chondrocytes resulting in joint pain and swelling.

The autonomic nervous system (ANS) plays an important role in the regulation of inflammation. Dysregulation of the ANS is observed in women treated for BCa.

Acupuncture, exercise, duloxetine, … have potential to improve AIA in BCa survivors, however, few studies have attempted to compare different modalities, resulting in a lack of evidence-based decision making for these interventions.

A novel, non-invasive, wearable vagus nerve stimulation device has been created and has the potential to modulate proinflammatory cytokine production and reduce inflammation by affecting the functioning of the autonomic nervous system.

Some studies have demonstrated the safety and efficacy of this device after several weeks of treatment, on the intensity of pain secondary to rheumatic diseases after several weeks of treatment.

We would like to study the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) for patients with aromatase inhibitor-induced arthralgia

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Menopausal women receiving an aromatase inhibitor (AI) as adjuvant treatment for breast cancer (letrozole (Femara), anastrozole (Arimidex) or exemestane (Aromasin)). The same AI must have been the same during the 4 weeks preceding inclusion and not be intended to be changed during the study period;
  2. Polyarticular and symmetrical pain that developed or worsened after the initiation of AI therapy and has persisted for at least 1 month;
  3. Score greater than 4 within 7 days before randomization (range,0-10; higher scores indicate greater pain) on the average pain item of the Brief Pain Inventory-Short Form (BPI-SF) as reported by patient;

  4. Patients receiving stable background analgesic treatment for AIA may be included, provided that this treatment has remained stable and that no new medication has been initiated prior to inclusion, as follows:

    • Analgesic treatment: stable for at least 2 weeks before inclusion, with no initiation of new medication.
    • Antidepressant treatment, including serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., duloxetine, venlafaxine): stable for at least 4 weeks before inclusion, with no initiation of new medication."
  5. Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2;
  6. Patient covered by a social security system;
  7. Patient mastering the French language and able to complete the evaluation questionnaires;
  8. Signed written informed consent form.

Exclusion Criteria:

  1. Patients who have previously used an electrostimulation device for pain management;
  2. Use of vagus nerve stimulation prior to the study;
  3. Patients who have received auriculotherapy for the same indication within the previous 4 weeks or who plan to initiate such treatment during the study;
  4. Symptomatic orthostatic hypotension (according to investigator) or recurrent vasovagal syncope or history of vagotomy;
  5. Previously implanted electrically active medical devices (eg, cardiac pacemakers or automatic implantable cardioverter defibrillators), or significant electrocardiogram abnormalities (cardiac rhythm disturbances, atrioventricular block >first degree or total bundle branch block);
  6. Current treatment with beta-blocker drugs;
  7. Patient under guardianship or unable to give informed consent;
  8. Patient unable to undergo medical follow-up for geographical, social or psychopathological reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental arm: active device

Participants assigned to the active taVNS arm received a transcutaneous auricular vagus nerve stimulation device delivering active electrical stimulation to the left auricular branch of the vagus nerve.

Stimulation intensity was progressively adjusted in 1-mA increments until the participant reported a slight pricking or tingling sensation or reached the maximum intensity.

Daily stimulation sessions were performed at home according to the study schedule
Device: Active taVNS (TENS ECO Plus)
Active taVNS delivered through a transcutaneous auricular vagus nerve stimulation device applied to the left ear. The device provides active electrical stimulation according to predefined stimulation parameters. Participants perform daily home stimulation sessions for the duration of the study.
Sham Comparator: Control arm : sham device

Participants assigned to the sham taVNS arm received an identical device with the same appearance and display as the active device but delivering no active electrical stimulation.

Stimulation intensity was simulated without producing perceptible electrical output, maintaining blinding of participants and staff.

Daily home sessions followed the same schedule and instructions as in the active arm
Device: Sham taVNS (TENS ECO Plus)
Sham taVNS delivered through a device identical in appearance and display to the active device but delivering no active electrical stimulation. Participants perform daily home sessions following the same schedule as the active group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 6 Weeks
Time Frame: 6 weeks

The primary endpoint is the proportion of participants who achieve a ≥30% reduction from baseline in the Brief Pain Inventory - Average Pain (BPI-AP) score.

The BPI-AP corresponds to the participant's average pain intensity over the past 7 days.

Baseline is defined as the BPI-AP score collected before initiation of the 6-week taVNS intervention.

Effectiveness of taVNS will be evaluated by comparing the response rate (≥30% pain reduction) at Week 6 with baseline values.
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 3 months
Time Frame: 3 months

The primary endpoint is the proportion of participants who achieve a ≥30% reduction from baseline in the Brief Pain Inventory - Average Pain (BPI-AP) score.

The BPI-AP corresponds to the participant's average pain intensity over the past 7 days.

Baseline is defined as the BPI-AP score collected before initiation of the 6-week taVNS intervention.

Effectiveness of taVNS will be evaluated by comparing the response rate (≥30% pain reduction) at 3 months with baseline values
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Cancerologie de l'Ouest

Investigators

  • Principal Investigator: François-Xavier PILOQUET, MD, Institut de cancerologie de l'ouest

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

May 4, 2026

First Submitted That Met QC Criteria

May 4, 2026

First Posted (Actual)

May 8, 2026

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICO-2025-14
  • 2026-a00387-44 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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