Non-invasive Vagus Nerve Stimulation for Chronic Musculoskeletal Pain

Starting soon · Not applicable · Has a placebo group

Conditions studied: Chronic Musculoskeletal Pain, Autonomic Dysfunction, Dysautonomia

In brief

Chronic musculoskeletal (MSK) pain affects an estimated 20-33% of the global population and is frequently associated with autonomic nervous system dysfunction, characterised by symptoms such as orthostatic intolerance, palpitations, gastrointestinal dysmotility, and fatigue. Conventional treatments often fail to address this autonomic component, limiting their effectiveness. This pilot study investigates whether non-invasive vagus nerve stimulation (nVNS) using the gammaCore Sapphire device can reduce autonomic symptom severity and improve pain in adults with chronic MSK pain and confirmed autonomic dysfunction. RESTORE-MSK is a randomised, single-blind, sham-controlled, crossover pilot study. Twelve participants with chronic MSK pain (lasting 12 weeks or longer) and autonomic dysfunction (COMPASS-31 score of 17 or more) will be recruited from musculoskeletal clinics at Chapel Allerton Hospital, Leeds. Participants will be randomly allocated to receive either active nVNS or sham stimulation first, followed by a 2-week washout period, then crossover to the alternative treatment. Each treatment period lasts 14 days, with participants self-administering the device twice daily (morning and evening). The primary outcome is change in autonomic symptom severity measured by the Composite Autonomic Symptom Score-31 (COMPASS-31). Secondary outcomes include physiological response to the NASA Lean Test, pain severity and interference (Brief Pain Inventory), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (EQ-5D-5L), intervention acceptability, and recruitment feasibility. This pilot study aims to establish feasibility and proof of concept for a larger randomised controlled trial investigating nVNS as a non-pharmacological treatment option for chronic MSK pain with autonomic dysfunction.

Key facts

Study ID

NCT07409363

Run by

University of Leeds

People needed

12

Starts

2026-05-14

Expected to finish

2026-07-31

Last updated by the study team

2026-05-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Individuals diagnosed with musculoskeletal (MSK) conditions and currently experiencing MSK pain lasting for 12 weeks or longer, in line with the ICD-11 criteria for chronic pain.
• Identified as having autonomic dysfunction (AD) defined as a score of 17 or more on the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire.
• Ability to understand and willingness to sign a written informed consent document.
• Stated willingness to comply with all study procedures and be available for the duration of the study (approximately 6 weeks).
• Ability to read and understand English sufficiently to complete study questionnaires.

You may not qualify if…

• Pregnancy (self-reported; safety of nVNS in pregnancy not established).
• Advanced heart disease, including: severe heart failure (NYHA Class III-IV), myocardial infarction within the preceding 6 months, or ongoing investigations for cardiac arrhythmias.
• Use of an active implantable medical device, including: cardiac pacemaker, implantable cardioverter-defibrillator (ICD), cochlear implant, hearing aid implant, or any other implanted electronic device.
• Concurrent use of another electrical stimulation device, including: transcutaneous electrical nerve stimulation (TENS) unit, muscle stimulator, or any other portable electronic stimulation device.
• Inability to provide informed consent.

Where it is running

• Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust, Chapeltown Road, Leeds, LS7 4SA, United Kingdom — Leeds, West Yorkshire, United Kingdom

Full record on ClinicalTrials.gov

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