Breast CancerAROVAGUENCT07575750
Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Aromatase Inhibitor-induced Arthralgia (AIA)
A study testing Active taVNS (TENS ECO Plus) in people with Breast Cancer and Aromatase Inhibitor-induced Arthralgia, run by Institut Cancerologie de l'Ouest at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Aromatase Inhibitor-induced Arthralgia
- What is being tested?
- Active taVNS (TENS ECO Plus)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2026to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
- 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 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."
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Marine TIGREAT contact
France1 site
Institut de Cancérologie de l'Ouest
Saint-Herblain, 44805
François-Xavier PILOQUET, MD, françois-xavier.piloquet@ico.unicancer.fr
About this study
Official title: 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.
Read more
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
- Being tested
- Active taVNS (TENS ECO Plus), Sham taVNS (TENS ECO Plus)
- Keywords
- Aromatase inhibitors, aromatase inhibitor-induced arthralgia, Breast cancer, transcutaneous auricular vagus nerve stimulation (taVNS), vagus nerve stimulation device
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm: active device | 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 Receives: Device: Active taVNS (TENS ECO Plus) |
| Control arm : sham device | 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 Receives: Device: Sham taVNS (TENS ECO Plus) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (1)
Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2026
- Study startSep 2026 (estimated)
- Primary completionNov 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François-Xavier PILOQUET, MD, Principal investigator, Institut de Cancérologie de l'Ouest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07575750
- Sponsor's protocol ID
- ICO-2025-14
- Other IDs
- 2026-a00387-44
- Acronym
- AROVAGUE
- Status last verified
- Apr 2026
- First submitted
- 4 May 2026
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Aromatase Inhibitor-induced Arthralgia (AIA): a Phase 2, Randomized, Monocentric, taVNS Versus Sham, Double Blind
- ClinicalTrials.gov ID
- NCT07575750
- Acronym / sponsor ID
- AROVAGUE / ICO-2025-14
- Keywords
- Aromatase inhibitors, aromatase inhibitor-induced arthralgia, Breast cancer, transcutaneous auricular vagus nerve stimulation (taVNS), vagus nerve stimulation device
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 8 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm: active device | Experimental | Device: Active taVNS (TENS ECO Plus)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 |
| Control arm : sham device | Sham comparator | Device: Sham taVNS (TENS ECO Plus)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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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;
- 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 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:
- Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2;
Key exclusion criteria (8 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Experimental arm: active 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. | Device | Control arm : sham device |
Primary outcome
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.
1 secondary outcome
Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 3 months
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marine TIGREAT contact
François-Xavier PILOQUET, MD principal investigator
Institut de Cancérologie de l'Ouest
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active taVNS (TENS ECO Plus) in people with Breast Cancer and Aromatase Inhibitor-induced Arthralgia, run by Institut Cancerologie de l'Ouest at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact François Xavier PILOQUET, MD (+33240679900 ext. +33, françois-xavier.piloquet@ico.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 6 Weeks (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.