Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Aromatase Inhibitor-induced Arthralgia (AIA) (AROVAGUE)
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
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Marine TIGREAT
- E-mail: marine.tigreat@ico.unicancer.fr
Undersøgelse Kontakt Backup
- Navn: François Xavier PILOQUET, MD
- Telefonnummer: +33 +33240679900
- E-mail: françois-xavier.piloquet@ico.unicancer.fr
Studiesteder
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Saint-Herblain, Frankrig, 44805
- Institut de Cancérologie de l'Ouest
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Kontakt:
- François-Xavier PILOQUET, MD
- E-mail: françois-xavier.piloquet@ico.unicancer.fr
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
Inclusion Criteria:
- 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."
- 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.
Exclusion Criteria:
- 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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Støttende pleje
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
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Eksperimentel: 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 |
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.
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Sham-komparator: 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 |
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.
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Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 6 Weeks
Tidsramme: 6 weeks
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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
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Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Proportion of Participants Achieving ≥30% Reduction in Average Pain Intensity (BPI-AP) From Baseline at 3 months
Tidsramme: 3 months
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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
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Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Ledende efterforsker: François-Xavier PILOQUET, MD, Institut de Cancérologie de l'Ouest
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- ICO-2025-14
- 2026-a00387-44 (Anden identifikator: ID-RCB)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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