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Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)NCT07593365

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

A study testing transcutaneous auricular vagus nerve stimulation in people with Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS) and Breast Cancer, run by Peking University People's Hospital at 1 site in China.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
transcutaneous auricular vagus nerve stimulation
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
216 participants
Where
1 siteChina
Study dates
6 May 2026to 31 Dec 2029
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

  • 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.

Who cannot join

  • 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;
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site
  • Peking University People's Hospital

    Beijing, Beijing Municipality, 100044

    Pei Li, M.D, +86-13126762029, pli@stu.pku.edu.cn

Other trials in China

About this study

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:

Read more
  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.

Being tested
transcutaneous auricular vagus nerve stimulation, sham stimulation
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • transcutaneous auricular vagus nerve stimulationDevice

    Also called taVNS

    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.

  • sham stimulationDevice

    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.

Study groups in NCT07593365
Study groupRoleWhat they receive
transcutaneous auricular vagus nerve stimulation groupActive comparatorElectrodes 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.
Receives: Device: transcutaneous auricular vagus nerve stimulation
sham stimulation groupSham comparatorCompared 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.
Receives: Device: sham stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (8)
  1. Pain relief rate at follow-up

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

  2. Dosage of analgesic drugs

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

  3. Depression scores

    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.

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

  4. Anxiety scores

    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.

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

  5. Quality of life score

    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.

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

  6. Plasma inflammatory marker levels

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

  7. The proportion of T cells in the blood

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

  8. The count of T cells in the blood

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2026
  2. Study start6 May 2026 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
216 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07593365
Sponsor's protocol ID
2026PHB256-001
Other IDs
82571385
Status last verified
May 2026
First submitted
5 May 2026
Last updated
18 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: To protect patient privacy and ensure the security of clinical data, the individual participant data (IPD) collected in this study will be used only for scientific analysis and publication related to this trial. No public disclosure, sharing, or uploading to public repositories is planned. Therefore, IPD will not be made available.

Publications

  • Zhang S, Zhao Y, Qin Z, Han Y, He J, Zhao B, Wang L, Duan Y, Huo J, Wang T, Wang Y, Rong P. Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Insomnia Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2024 Dec 2;7(12):e2451217. doi: 10.1001/jamanetworkopen.2024.51217.

    PubMed 39680406
  • Zhang Q, Hresko ME, Picton LK, Su L, Hollander MJ, Nunez-Cruz S, Zhang Z, Assenmacher CA, Sockolosky JT, Garcia KC, Milone MC. A human orthogonal IL-2 and IL-2Rbeta system enhances CAR T cell expansion and antitumor activity in a murine model of leukemia. Sci Transl Med. 2021 Dec 22;13(625):eabg6986. doi: 10.1126/scitranslmed.abg6986. Epub 2021 Dec 22.

    PubMed 34936380
  • Ren Z, Zhang A, Sun Z, Liang Y, Ye J, Qiao J, Li B, Fu YX. Selective delivery of low-affinity IL-2 to PD-1+ T cells rejuvenates antitumor immunity with reduced toxicity. J Clin Invest. 2022 Feb 1;132(3):e153604. doi: 10.1172/JCI153604.

    PubMed 35104810
  • Miao M, Li Y, Huang B, Chen J, Jin Y, Shao M, Zhang X, Sun X, He J, Li Z. Treatment of Active Idiopathic Inflammatory Myopathies by Low-Dose Interleukin-2: A Prospective Cohort Pilot Study. Rheumatol Ther. 2021 Jun;8(2):835-847. doi: 10.1007/s40744-021-00301-3. Epub 2021 Apr 14.

    PubMed 33852146
  • Zhang X, Miao M, Zhang R, Liu X, Zhao X, Shao M, Liu T, Jin Y, Chen J, Liu H, Zhang X, Li Y, Zhou Y, Yang Y, Li R, Yao H, Liu Y, Li C, Li Y, Ren L, Su Y, Sun X, He J, Li Z. Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial. Signal Transduct Target Ther. 2022 Mar 7;7(1):67. doi: 10.1038/s41392-022-00887-2.

    PubMed 35250032
  • He J, Chen J, Miao M, Zhang R, Cheng G, Wang Y, Feng R, Huang B, Luan H, Jia Y, Jin Y, Zhang X, Shao M, Wang Y, Zhang X, Li J, Zhao X, Wang H, Liu T, Xiao X, Zhang X, Su Y, Mu R, Ye H, Li R, Liu X, Liu Y, Li C, Liu H, Hu F, Guo J, Liu W, Zhang WB, Jacob A, Ambrus JL Jr, Ding C, Yu D, Sun X, Li Z. Efficacy and Safety of Low-Dose Interleukin 2 for Primary Sjogren Syndrome: A Randomized Clinical Trial. JAMA Netw Open. 2022 Nov 1;5(11):e2241451. doi: 10.1001/jamanetworkopen.2022.41451.

    PubMed 36355371
  • He J, Zhang X, Wei Y, Sun X, Chen Y, Deng J, Jin Y, Gan Y, Hu X, Jia R, Xu C, Hou Z, Leong YA, Zhu L, Feng J, An Y, Jia Y, Li C, Liu X, Ye H, Ren L, Li R, Yao H, Li Y, Chen S, Zhang X, Su Y, Guo J, Shen N, Morand EF, Yu D, Li Z. Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus. Nat Med. 2016 Sep;22(9):991-3. doi: 10.1038/nm.4148. Epub 2016 Aug 8.

    PubMed 27500725
  • Yang Y, Zhang R, Zhong Z, Li J, Feng Y. Efficacy of transauricular vagus nerve stimulation for the treatment of chemotherapy-induced painful peripheral neuropathy: a randomized controlled exploratory study. Neurol Sci. 2024 May;45(5):2289-2300. doi: 10.1007/s10072-023-07229-2. Epub 2023 Dec 8.

    PubMed 38063922
  • Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.

    PubMed 30217648
  • Abdullahi A, Wong TWL, Ng SSM. Putative role of non-invasive vagus nerve stimulation in cancer pathology and immunotherapy: Can this be a hidden treasure, especially for the elderly? Cancer Med. 2023 Sep;12(18):19081-19090. doi: 10.1002/cam4.6466. Epub 2023 Aug 17.

    PubMed 37587897
  • Shi X, Hu Y, Zhang B, Li W, Chen JD, Liu F. Ameliorating effects and mechanisms of transcutaneous auricular vagal nerve stimulation on abdominal pain and constipation. JCI Insight. 2021 Jul 22;6(14):e150052. doi: 10.1172/jci.insight.150052.

    PubMed 34138761
  • Barbanti P, Grazzi L, Egeo G, Padovan AM, Liebler E, Bussone G. Non-invasive vagus nerve stimulation for acute treatment of high-frequency and chronic migraine: an open-label study. J Headache Pain. 2015;16:61. doi: 10.1186/s10194-015-0542-4. Epub 2015 Jun 30.

    PubMed 26123825
  • Arem H, Sorkin M, Cartmel B, Fiellin M, Capozza S, Harrigan M, Ercolano E, Zhou Y, Sanft T, Gross C, Schmitz K, Neogi T, Hershman D, Ligibel J, Irwin ML. Exercise adherence in a randomized trial of exercise on aromatase inhibitor arthralgias in breast cancer survivors: the Hormones and Physical Exercise (HOPE) study. J Cancer Surviv. 2016 Aug;10(4):654-62. doi: 10.1007/s11764-015-0511-6. Epub 2016 Jan 19.

    PubMed 26782031
  • van Hellemond IEG, Geurts SME, Tjan-Heijnen VCG. Current Status of Extended Adjuvant Endocrine Therapy in Early Stage Breast Cancer. Curr Treat Options Oncol. 2018 Apr 27;19(5):26. doi: 10.1007/s11864-018-0541-1.

    PubMed 29704066

Questions about this trial

What is this clinical trial studying?

A study testing transcutaneous auricular vagus nerve stimulation in people with Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS) and Breast Cancer, run by Peking University People's Hospital at 1 site in China.

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 8 inclusion and 13 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 18 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 China. 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 Yi Feng, M.D (+86-010-88325590, fengyi@pkuph.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07593365, which also lists 14 linked publications.

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 18 May 2026.

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