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NCT Number: NCT07593365

Clinical Application of Vagus Nerve Stimulation Combined With Immunoregulatory T Cells in Alleviating Aromatase Inhibitor-Induced Pain

The goal of this clinical trial is to learn whether transcutaneous auricular vagus nerve stimulation, also called taVNS, can help relieve aromatase inhibitor-related joint and muscle pain in adult women with hormone receptor-positive breast cancer.

The main questions this study aims to answer are:

1. Does taVNS reduce pain caused by aromatase inhibitor treatment? 2. Does taVNS improve quality of life, mood symptoms, and the need for pain medicine? 3. What side effects or medical problems occur during treatment?

Researchers will compare active taVNS with sham stimulation. Participants in both groups will receive mild electrical stimulation around the ear, but the sham stimulation will be applied to an area not expected to activate the vagus nerve.

Participants will:

1. Be randomly assigned to active taVNS or sham stimulation 2. Receive one 30-minute treatment session every day for 28 days 3. Complete pain, mood, and quality-of-life questionnaires before treatment, after treatment, and during follow-up 4. Report pain medicine use and any side effects 5. Provide small blood samples to measure inflammatory markers, T-cell profiles, and tumor markers

Participants will be followed for up to 6 months after treatment. For some participants who do not have enough pain relief after taVNS, an optional second-stage study may be offered. In this stage, participants may receive low-dose interleukin-2, also called IL-2, by injection every other day for 2 weeks.

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Key information

Conditions

Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS) Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Pain Alleviation Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Female participants aged over 18 years;
  • Patients with pathologically confirmed stage I-III primary breast cancer;
  • Patients who have recovered from systemic symptoms related to surgery, radiotherapy, or chemotherapy;
  • Patients with estrogen receptor- and/or progesterone receptor-positive breast cancer who are receiving aromatase inhibitor therapy and have aromatase inhibitor-related musculoskeletal pain, with a score greater than 3 on the Worst Pain item of the Brief Pain Inventory (BPI-WP);
  • Patients who have received aromatase inhibitor therapy for more than 30 days and are expected to continue treatment for more than 1 year;
  • Patients who voluntarily agree to participate in this study and sign the informed consent form.

For participants receiving combined IL-2 treatment, the following additional criterion applies:

  • Pain relief rate of less than 50% after taVNS treatment and a lower peripheral blood Treg count than before treatment.

Exclusion criteria

  • Patients with advanced breast cancer;
  • Patients with other significant organ dysfunction, such as major cardiovascular disease, diabetes mellitus, or hyperthyroidism;
  • Patients with other cancers;
  • Patients with a history of fracture or surgery around the painful joint area within the past 6 months;
  • Patients currently receiving corticosteroids or opioid therapy;
  • Patients with contraindications to vagus nerve stimulation;
  • Patients who are unable to communicate normally, such as those with cognitive impairment or hearing impairment;
  • Patients who have participated in another clinical trial within the past 1 month.

For participants receiving combined IL-2 treatment, the following additional exclusion criteria apply:

  • Severe cardiac or renal disease, or hematologic disease;
  • Previous IL-2-related toxic reaction or allergy;
  • Use of other biologic agents or immunosuppressive drugs within the past 1 month;
  • Any other condition that the investigator considers unsuitable for study participation.

Treatment and study plan

Transcutaneous Auricular Vagus Nerve Stimulation

Device

Electrodes will be placed on specific areas of the participant's left external ear that are mainly innervated by the auricular branch of the vagus nerve. The electrodes will be connected to an electrical stimulation device, and stimulation will be delivered at tolerable intensity using preset study parameters. Treatment will be given once daily for 28 consecutive days.

Other names: taVNS

Sham stimulation

Device

Compared with transcutaneous auricular vagus nerve stimulation group, electrodes will be placed on different areas of the participant's left external ear that are not innervated by the auricular branch of the vagus nerve. The electrodes will be connected to an electrical stimulation device, and stimulation will be delivered at tolerable intensity using preset study parameters. Treatment will be given once daily for 28 consecutive days.

Primary outcomes

  1. The pain relief rate of patients at the end of the 4-week treatment period

    Time frame: From enrollment to the end of treatment at 4 weeks.

Secondary outcomes

  1. Pain relief rate at follow-up

    Time frame: At 1, 2, 3, and 6 months after completion of treatment.

  2. Dosage of analgesic drugs

    Time frame: At 1, 2, 3, and 6 months after completion of treatment.

  3. Depression scores

    Time frame: At 1, 2, 3, and 6 months after completion of treatment.

    PHQ-9 is used to measure depression. PHQ-9 ( unabbreviated scale title: Patient Health Questionnaire-9) Minimum Value: 0 Maximum Value: 27 Score Interpretation: Higher scores mean a WORSE outcome. Details:The PHQ-9 is a screening tool for depression. A higher score indicates more severe depressive symptoms. Generally, scores are interpreted as follows: 0-4 (Minimal), 5-9 (Mild), 10-14 (Moderate), 15-19 (Moderately Severe), and 20-27 (Severe) depression.

  4. Anxiety scores

    Time frame: At 1, 2, 3, and 6 months after completion of treatment.

    GAD-7 is used to measure anxiety. GAD-7 (unabbreviated scale title: Generalized Anxiety Disorder-7) Minimum Value: 0 Maximum Value: 21 Score Interpretation: Higher scores mean a WORSE outcome. Details:The GAD-7 measures the severity of generalized anxiety disorder. A higher score reflects more frequent and severe anxiety symptoms. Typical interpretations are: 0-4 (Minimal), 5-9 (Mild), 10-14 (Moderate), and 15-21 (Severe) anxiety.

  5. Quality of life score

    Time frame: At 1, 2, 3, and 6 months after completion of treatment.

    Quality of life assessed by the EuroQol 5-Dimension 5-Level questionnaire and EuroQol Visual Analogue Scale

    Description:

    Quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) and the EuroQol Visual Analogue Scale (EQ VAS). For the EQ-5D-5L descriptive system, scores range from 5 to 25, with higher scores indicating worse health status. For the EQ VAS, scores range from 0 to 100, with higher scores indicating better self-rated health status.

  6. Plasma inflammatory marker levels

    Time frame: Baseline, immediately after completion of treatment, and 6 months after completion of treatment.

  7. The proportion of T cells in the blood

    Time frame: Baseline, immediately after completion of treatment, and 6 months after completion of treatment.

  8. The count of T cells in the blood

    Time frame: Baseline, immediately after completion of treatment, and 6 months after completion of treatment.

Other outcomes

  1. Tumor marker levels

    Time frame: Baseline, immediately after completion of treatment, and 6 months after completion of treatment.

  2. Adverse events and serious adverse events

    Time frame: Adverse events and serious adverse events will be recorded throughout the study.

Study contacts

Contact information is provided by the study sponsor or research team.

Pei Li, M.D

CONTACT

[email protected]

+86-13126762029

Yi Feng, M.D

CONTACT

[email protected]

+86-010-88325590

Sponsors and collaborators

Lead sponsor

Peking University People's Hospital

Other

Collaborators

  • National Natural Science Foundation of China

Registry information

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
May 18, 2026
Registry last updated
May 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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