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

NCT07575750 | Not Yet Recruiting

• 2 other identifiers: ICO-2025-142026-a00387-44
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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 (1). 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 (2). 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 (3,4). 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 (5,6). 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 (7,8). We would like to study the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) for patients with aromatase inhibitor-induced arthralgia

Conditions

Breast Cancer; Aromatase Inhibitor-induced Arthralgia

Keywords

Aromatase inhibitors; aromatase inhibitor-induced arthralgia; Breast cancer; transcutaneous auricular vagus nerve stimulation (taVNS); vagus nerve stimulation device

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 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 Outcomes (1)

• Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 3 months

  3 months

Study Arms (2)

Experimental arm

EXPERIMENTAL

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)

Control arm

SHAM COMPARATOR

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)

Interventions

Active taVNS (TENS ECO Plus) DEVICE

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.

Experimental arm

Sham taVNS (TENS ECO Plus) DEVICE

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.

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Polyarticular and symmetrical pain that developed or worsened after the initiation of AI therapy and has persisted for at least 1 month;
• 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;
• Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2;
• Patient covered by a social security system;
• Patient mastering the French language and able to complete the evaluation questionnaires;
• Signed written informed consent form.

You may not qualify if:

• Patients who have previously used an electrostimulation device for pain management;
• Use of vagus nerve stimulation prior to the study;
• Patients who have received auriculotherapy for the same indication within the previous 4 weeks or who plan to initiate such treatment during the study;
• Symptomatic orthostatic hypotension (according to investigator) or recurrent vasovagal syncope or history of vagotomy;
• 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);
• Current treatment with beta-blocker drugs;
• Patient under guardianship or unable to give informed consent;
• Patient unable to undergo medical follow-up for geographical, social or psychopathological reasons.

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (1)

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44805, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• François-Xavier PILOQUET, MD

  Institut de Cancérologie de l'Ouest

  PRINCIPAL INVESTIGATOR

Central Study Contacts

François Xavier PILOQUET, MD

CONTACT

+33240679900; françois-xavier.piloquet@ico.unicancer.fr

Marine TIGREAT

CONTACT

marine.tigreat@ico.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, investigators, and outcome assessors were blinded to treatment assignment. Both the active and sham taVNS devices were identical in appearance and interface. The sham device displayed the same signals and indicators as the active device but delivered no active stimulation. This design ensured maintenance of blinding for all masked roles throughout the study
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: May 8, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 8, 2026

Record last verified: 2026-04

Locations

FR (1)