FibromyalgiaR61VNSNCT07904351
Toward Biomarker-Guided Fibromyalgia Treatment With Non-Invasive Vagus Nerve Stimulation
A study testing Transcutaneous Vagus Nerve Stimulation in people with Fibromyalgia, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Fibromyalgia is a syndrome with clinical symptoms that affect multiple systems of the body. Although basic science research and clinical research trials have been carried out, the cause and the mechanism of fibromyalgia are still unknown. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Transcutaneous Vagus Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2026to 31 Aug 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is 18 to 80 years old, including both male and female subjects.
- Subject has a documented diagnosis of FM for at least three months. This requirement is to avoid the uncertainty of an unstable pain condition and to minimize the study variation.
- Subject has a pain score of 4 or above (numeric pain score: 0 - 10 from no pain to worst pain).
Who cannot join
- Subject has current cardiac arrhythmia or had implanted cardiac pacemaker or AICD device.
- Subject has major psychiatric disorder required hospitalization in the last 3 months.
- Subject has active infection at the site of device application.
- Subject has recurrent syncope symptoms within the past three months.
- Subject is pregnant.
- Subject has had VNS treatment within the past two months.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Lucy Chen, M.D. contact
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
Melissa Difuntorum, B.S., 6177246102, mdifuntorum@mgh.harvard.edu
Lucy Chen, M.D., llchen@mgh.harvard.edu
About this study
Fibromyalgia is a syndrome with clinical symptoms that affect multiple systems of the body. Although basic science research and clinical research trials have been carried out, the cause and the mechanism of fibromyalgia are still unknown. The goal of current medical treatment is to relieve symptoms and improve quality of life. Recent clinical and experimental studies have shown that stimulation of the vagus nerve has a potential to help pain syndromes. In this study, we aim to evaluate the effects of using transcutaneous vagus nerve stimulation (tVNS) on treating pain and other symptoms in fibromyalgia patients. We will do this by using the VagaCalm device.
Read the detailed description
Fibromyalgia is a chronic condition that can cause widespread pain, fatigue, sleep problems, anxiety, and depression. While current treatments can help manage symptoms, many people continue to experience significant discomfort and reduced quality of life.
This study will evaluate whether transcutaneous vagus nerve stimulation (tVNS), a non-invasive therapy that delivers mild electrical stimulation to the outer ear, can help reduce pain and other symptoms in people with fibromyalgia. The vagus nerve helps regulate communication between the brain and the body and may play a role in pain processing.
A total of 105 participants will take part in this 6-week study. Participants will receive either active tVNS treatment or a sham (inactive) treatment for comparison. Researchers will assess changes in pain and other fibromyalgia-related symptoms using questionnaires and pain sensitivity testing. Additional assessments will include pressure pain testing, mechanical pain sensitivity testing using Von Frey filaments, dietary questionnaires, the Bristol Stool Chart, and stool sample collection.
The study will also measure levels of intestinal alkaline phosphatase (IAP) in stool samples to investigate whether IAP could serve as a biomarker for fibromyalgia and whether it may be associated with symptom severity or response to treatment. Participants will complete a follow-up phone call approximately 8 weeks after enrollment to assess pain levels and any side effects.
The findings may improve understanding of fibromyalgia, help identify potential biological markers of the condition, and evaluate a non-invasive treatment approach for symptom management.
- Conditions
- Fibromyalgia
- Being tested
- Transcutaneous Vagus Nerve Stimulation
- Keywords
- Vagus nerve stimulation, Pain, Fibromyalgia symptoms
- Medical subject headings
- Fibromyalgia, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Vagus Nerve StimulationDevice
30 minutes stimulation, twice per day for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Transcutaneous Vagus Nerve Stimulation (tVNS) | Experimental | Receive tVNS 30 minutes per session, twice/day for 6 weeks and maintain regular medication treatment without change. Post study follow up will occur 2 weeks after completing the 6-week treatment. Receives: Device: Transcutaneous Vagus Nerve Stimulation |
| Sham Control Group | No intervention | Receive sham point stimulation 30 minutes per session, twice/day for 6 weeks and maintain regular medication treatment without change. Post study follow up will occur 2 weeks after completing the 6-week treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Score
The SF-MPQ-2 assesses pain quality and intensity across multiple pain domains and includes a general pain intensity rating. Participants rate pain severity on a scale from 0 (none) to 10 (worst possible). Higher scores indicate greater pain severity.
Measured: Week 0 and Week 6
Secondary outcomes (8)
Multidimensional Fatigue Inventory
The Multidimensional Fatigue Inventory (MFI-20) is a 20-item self-report questionnaire that assesses general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Participants rate statements using a 5-point Likert scale. Higher total scores indicate greater fatigue.
Measured: Week 0 and Week 6
Revised Fibromyalgia Impact Questionnaire (FIQR) Total Score
The Revised Fibromyalgia Impact Questionnaire (FIQR) is a 21-item self-report measure assessing fibromyalgia-related function, overall impact, and symptoms during the previous 7 days. Total scores range from 0 to 100, with higher scores indicating greater fibromyalgia symptom burden and functional impairment.
Measured: Week 0 and Week 6
Supplemental Gastrointestinal Symptom Questionnaire Score
The Supplemental Gastrointestinal Symptom Questionnaire assesses gastrointestinal symptoms, including abdominal pain, bloating, abnormal bowel movements, irritable bowel syndrome diagnosis, and stool characteristics. Higher scores indicate greater gastrointestinal symptom burden.
Measured: Week 0 and Week 6
Empirical Dietary Inflammatory Index (EDII) Score
The Empirical Dietary Inflammatory Index (EDII) is a dietary assessment questionnaire that evaluates the inflammatory potential of dietary intake based on the frequency of consumption of specific food and beverage categories. Higher scores indicate a more pro-inflammatory dietary pattern.
Measured: Week 0 and Week 6
Medical Outcomes Study Questionnaire Short Form 36 (SF-36)
The SF-36 is a 36-item self-report measure of health-related quality of life assessing physical functioning, role limitations, bodily pain, general health, vitality, social functioning, emotional well-being, and mental health. Higher scores indicate better health status and quality of life.
Measured: Week 0 and Week 6
Medical Outcomes Study (MOS) Sleep Scale Score
The MOS Sleep Scale is a 12-item self-report questionnaire that assesses sleep disturbance, sleep adequacy, daytime somnolence, sleep quantity, and other sleep-related problems experienced during the previous 4 weeks. Higher scores indicate greater sleep disturbance and poorer sleep quality.
Measured: Week 0 and Week 6
Blood inflammation marker
Collect blood samples for cytokine level assessment.
Measured: Week 0 and Week 6
Assessment of Gut Microbiome Changes Through Genomic and Phenotypic Analysis
Collect stool samples to analyze bacterial composition and metabolomic profiles of the gut microbiome.
Measured: Week 0 and Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2026
- Study start15 Oct 2026 (estimated)
- Primary completion30 Jul 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 8-weeks of clinical study with a total of 105 subjects, randomized into 2 groups (70 subjects in tVNS and 35 subjects in control group)
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Lucy Chen, Massachusetts General Hospital
- Investigators
- Lucy Chen, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07904351
- Sponsor's protocol ID
- 2026P002572
- Other IDs
- 1R61AR086955-01A1
- Acronym
- R61VNS
- Status last verified
- Sep 2026
- First submitted
- 23 Oct 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Maffei ME. Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies. Int J Mol Sci. 2020 Oct 23;21(21):7877. doi: 10.3390/ijms21217877.
PubMed 33114203Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I. Headache. 2016 Jan;56(1):71-8. doi: 10.1111/head.12647. Epub 2015 Sep 14.
PubMed 26364692Moisset X, Lanteri-Minet M, Fontaine D. Neurostimulation methods in the treatment of chronic pain. J Neural Transm (Vienna). 2020 Apr;127(4):673-686. doi: 10.1007/s00702-019-02092-y. Epub 2019 Oct 21.
PubMed 31637517
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Toward Biomarker-Guided Fibromyalgia Treatment With Non-Invasive Vagus Nerve Stimulation
- ClinicalTrials.gov ID
- NCT07904351
- Acronym / sponsor ID
- R61VNS / 2026P002572
- Conditions
- Fibromyalgia
- Keywords
- Vagus nerve stimulation, Pain, Fibromyalgia symptoms
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 15 Oct 2026 (estimated)
- Primary completion
- 30 Jul 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 29 Oct 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.
Fibromyalgia is a syndrome with clinical symptoms that affect multiple systems of the body. Although basic science research and clinical research trials have been carried out, the cause and the mechanism of fibromyalgia are still unknown. The goal of current medical treatment is to relieve symptoms and improve quality of life. Recent clinical and experimental studies have shown that stimulation of the vagus nerve has a potential to help pain syndromes. In this study, we aim to evaluate the effects of using transcutaneous vagus nerve stimulation (tVNS) on treating pain and other symptoms in fibromyalgia patients. We will do this by using the VagaCalm device.
Detailed description
Fibromyalgia is a chronic condition that can cause widespread pain, fatigue, sleep problems, anxiety, and depression. While current treatments can help manage symptoms, many people continue to experience significant discomfort and reduced quality of life.
This study will evaluate whether transcutaneous vagus nerve stimulation (tVNS), a non-invasive therapy that delivers mild electrical stimulation to the outer ear, can help reduce pain and other symptoms in people with fibromyalgia. The vagus nerve helps regulate communication between the brain and the body and may play a role in pain processing.
A total of 105 participants will take part in this 6-week study. Participants will receive either active tVNS treatment or a sham (inactive) treatment for comparison. Researchers will assess changes in pain and other fibromyalgia-related symptoms using questionnaires and pain sensitivity testing. Additional assessments will include pressure pain testing, mechanical pain sensitivity testing using Von Frey filaments, dietary questionnaires, the Bristol Stool Chart, and stool sample collection.
The study will also measure levels of intestinal alkaline phosphatase (IAP) in stool samples to investigate whether IAP could serve as a biomarker for fibromyalgia and whether it may be associated with symptom severity or response to treatment. Participants will complete a follow-up phone call approximately 8 weeks after enrollment to assess pain levels and any side effects.
The findings may improve understanding of fibromyalgia, help identify potential biological markers of the condition, and evaluate a non-invasive treatment approach for symptom management.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 8-weeks of clinical study with a total of 105 subjects, randomized into 2 groups (70 subjects in tVNS and 35 subjects in control group)
| Arm | Type | Receives |
|---|---|---|
| Transcutaneous Vagus Nerve Stimulation (tVNS) | Experimental | Device: Transcutaneous Vagus Nerve StimulationReceive tVNS 30 minutes per session, twice/day for 6 weeks and maintain regular medication treatment without change. Post study follow up will occur 2 weeks after completing the 6-week treatment. |
| Sham Control Group | No intervention | –Receive sham point stimulation 30 minutes per session, twice/day for 6 weeks and maintain regular medication treatment without change. Post study follow up will occur 2 weeks after completing the 6-week treatment. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subject is 18 to 80 years old, including both male and female subjects.
- Subject has a documented diagnosis of FM for at least three months. This requirement is to avoid the uncertainty of an unstable pain condition and to minimize the study variation.
- Subject has a pain score of 4 or above (numeric pain score: 0 - 10 from no pain to worst pain).
Key exclusion criteria (6 listed)
- Subject has current cardiac arrhythmia or had implanted cardiac pacemaker or AICD device.
- Subject has major psychiatric disorder required hospitalization in the last 3 months.
- Subject has active infection at the site of device application.
- Subject has recurrent syncope symptoms within the past three months.
- Subject is pregnant.
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 |
|---|---|---|
| Transcutaneous Vagus Nerve Stimulation30 minutes stimulation, twice per day for 6 weeks | Device | Transcutaneous Vagus Nerve Stimulation (tVNS) |
Primary outcome
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Score
Time frame: Week 0 and Week 6
The SF-MPQ-2 assesses pain quality and intensity across multiple pain domains and includes a general pain intensity rating. Participants rate pain severity on a scale from 0 (none) to 10 (worst possible). Higher scores indicate greater pain severity.
8 secondary outcomes
Multidimensional Fatigue Inventory
Time frame: Week 0 and Week 6
Revised Fibromyalgia Impact Questionnaire (FIQR) Total Score
Time frame: Week 0 and Week 6
Supplemental Gastrointestinal Symptom Questionnaire Score
Time frame: Week 0 and Week 6
Empirical Dietary Inflammatory Index (EDII) Score
Time frame: Week 0 and Week 6
Medical Outcomes Study Questionnaire Short Form 36 (SF-36)
Time frame: Week 0 and Week 6
Medical Outcomes Study (MOS) Sleep Scale Score
Time frame: Week 0 and Week 6
Blood inflammation marker
Time frame: Week 0 and Week 6
Assessment of Gut Microbiome Changes Through Genomic and Phenotypic Analysis
Time frame: Week 0 and Week 6
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 2 Nov 2026.
- Background: PubMed 33114203Maffei ME. Fibromyalgia: Recent Advances in Diagnosis, Classification, Pharmacotherapy and Alternative Remedies. Int J Mol Sci. 2020 Oct 23;21(21):7877. doi: 10.3390/ijms21217877.
- Background: PubMed 26364692Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I. Headache. 2016 Jan;56(1):71-8. doi: 10.1111/head.12647. Epub 2015 Sep 14.
- Background: PubMed 31637517Moisset X, Lanteri-Minet M, Fontaine D. Neurostimulation methods in the treatment of chronic pain. J Neural Transm (Vienna). 2020 Apr;127(4):673-686. doi: 10.1007/s00702-019-02092-y. Epub 2019 Oct 21.
- Individual participant dataSharing planned: No
Related trials for Fibromyalgia
Active, not recruiting
Objective Measurement of Pain Regulation in Individuals Who Have Received Internet-delivered Exposure-based Cognitive Behavior Therapy
Fibromyalgia
Enrolling by invitationPhase 3
Open-Label Safety Study of AXS-14 in Subjects With Fibromyalgia
Fibromyalgia
Recruiting
Exercise Interventions and Dietary Advice in Fibromyalgia and IBS
Fibromyalgia, Irritable Bowel Syndrome
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Recruiting
Auricular Acupuncture for Autonomic Balance and Pain in Fibromyalgia
Fibromyalgia Syndrome
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.
Lucy Chen, M.D. contact
Lucy Chen, M.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous Vagus Nerve Stimulation in people with Fibromyalgia, run by Massachusetts General Hospital at 1 site in United States.
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 3 inclusion and 6 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 2 Nov 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 United States. 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. 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 Melissa Difuntorum, BS (617-724-6102, mdifuntorum@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) Score (time frame: Week 0 and Week 6). 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 NCT07904351, which also lists 3 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 2 Nov 2026.