Post-Treatment Lyme DiseaseNCT05776251
taVNS for Persistent Symptoms From Lyme Disease
A study testing taVNS in people with Post-Treatment Lyme Disease, run by Columbia University at 1 site in United States.
Trial summary
This study is one of the first studies to investigate a non-antibiotic approach to the treatment of symptoms that persist after antibiotic treatment for Lyme disease (PTLS). Transcutaneous auricular vagus nerve stimulation (taVNS) offers the potential of being an effective and non-toxic approach to reduce the burden… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post-Treatment Lyme Disease
- What is being tested?
- taVNS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2023to Dec 2026
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of either Definite or Highly Probable Past Lyme disease diagnosed and treated by a health care provider more than 6 months previously.
- Have one or more current symptoms attributed to Lyme disease that were also present during the initial 6-month period after diagnosis and antibiotic treatment of Lyme disease.
- Individuals reporting that current symptoms cause clinically significant distress or impairment in functioning.
- Previously treated for Lyme disease with at least two courses of antibiotics considered appropriate for Lyme disease.
- Individuals who agree to not start a new medical or psychiatric treatment (that might impact study outcomes) for their chronic symptoms during the course of this study (unless deemed necessary by their primary care physician (PCP)).
- Individuals whose current treatment (that might impact study outcomes) has been stable for at least 6 weeks prior to baseline visit.
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- Lives in the U.S. and owns a smartphone, tablet or computer with Internet access.
- Able to read and understand English to be able to provide informed consent.
- Able and willing to come to Columbia University Irving Medical Center in NYC for 3-5 study visits.
- Willingness to have a 12-lead electrocardiogram (EKG) when evaluated on site and, if an EKG was conducted in the past year, willingness to try to obtain that EKG for us to review.
- Current moderate to severe fatigue. At least moderate intensity at study screening (a score of 4 or more on the Fatigue Severity Scale (FSS)).
- Ability to allocate sufficient time for the treatment sessions, including 6 sessions that will be monitored during work hours (8 am to 6 pm).
Who cannot join
- Current or past history of cardiovascular disorder(s) (coronary artery disease, peripheral artery disease, stroke, aortic disease, or other major cardiac condition). A history within the last year of unexplained fainting spells or of vasovagal syncope or feeling faint in response to medical settings or pain. Symptomatic bradycardia, orthostatic (postural) hypotension not correctable by fluid intake (i.e., a drop of >20 mm Hg systolic, 10 mm Hg diastolic or both), or persistent hypotension (BP below 90 mmHg systolic).
- Abnormal EKG findings (e.g., significant bradycardia) considered significant by a cardiologist.
- A diagnosed current major central nervous system disease (e.g., multiple sclerosis (MS), epilepsy, neurodegenerative diseases, ischemic stroke, Parkinson's, traumatic brain injury with cognitive impairment, etc.) or a history of brain surgery or brain tumors.
- A current psychiatric disorder that might impact treatment compliance (e.g., bipolar disorder, psychosis, substance abuse).
- Suicidal ideation with method, plan or intent in the last 6 months or a lifetime history of suicidal behavior.
- Current moderate-severe or severe depression (T-score of 65 or higher on the PROMIS-Emotional Distress-Depression SF) at screening.
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- Current serious unstable medical illness.
- Currently taking opiate-based medication or have taken antibiotics in the last 6 weeks for tick-borne illness.
- Ear-related: a) facial or ear pain; b) recent ear trauma; c) damage to left or right ear or anatomy that does not allow taVNS; d) ear infection (otitis media or externa); e) scar or inflammation on ear; f) Cochlear implants.
- Currently or recently (within 6 months) in a clinical trial of an investigational medicinal product or another medical device.
- Females who are pregnant or planning to become pregnant during the course of this study.
- Unable to connect to the Internet during treatment phase.
- Individuals with an active external or implanted electrical medical device (e.g., cardiac pacemaker, hearing aid implant) or any metal implant above the level of the neck.
- Individuals who have had surgery to cut the vagus nerve in the neck (cervical vagotomy).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Lyme and Tick-Borne Diseases Research Center
New York, New York, 10032
Brian A. Fallon, MD, 646-774-7503, baf1@columbia.edu
Mara Kuvaldina, PhD, 646-774-7503, mk4480@cumc.columbia.edu
About this study
Official title: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for Persistent Symptoms From Lyme Disease: a Feasibility, Tolerability, and Safety Study
This study is one of the first studies to investigate a non-antibiotic approach to the treatment of symptoms that persist after antibiotic treatment for Lyme disease (PTLS). Transcutaneous auricular vagus nerve stimulation (taVNS) offers the potential of being an effective and non-toxic approach to reduce the burden of multisystem symptoms in patients with PTLS. This study seeks to address an important goal: to assess the safety, feasibility, and tolerability of a new non-invasive, non-pharmacologic treatment for patients with symptoms that persist despite prior antibiotic treatment for Lyme disease.
Read the detailed description
Musculoskeletal pain, fatigue, and cognitive and mood problems are common persistent disabling symptoms among individuals with post-treatment Lyme Disease. Each year in the United States, approximately 476,000 individuals are newly diagnosed with Lyme disease and 10-20% of these go on to have persistent or relapsing symptoms that are not responding to the current best antibiotic therapies.
Individuals with persistent infection are likely to respond best to additional antibiotic therapy. Individuals with post- infectious causes require other approaches - such as ones that impact ongoing inflammation or altered neural circuits and metabolism. Safe and effective treatment for these individuals with persistent symptoms represents a prominent unmet need.
Vagus nerve stimulation (VNS) may be a treatment with considerable impact for patients with post-treatment Lyme disease. The vagus nerve (the 10th and longest cranial nerve) impacts the central nervous system, the autonomic nervous system (e.g, heart, lungs, digestive tract), and the systemic inflammatory response. It has also been shown to play a role in cognition, pain, mood disorders, inflammation, and immune function. Research over the last 2 decades has demonstrated that electrical stimulation of the vagus nerve can have multiple salutary effects in both animal models of disease and human illness. Until very recently, VNS has been considered an invasive intervention, reserved for patients with refractory disease, as it requires surgery to implant the device; this approach is costly and puts patients at risk of infection and other complications. These factors have limited the accessibility and broad application of VNS. A non-invasive approach to VNS would increase affordability, accessibility, and decrease risk. This is now possible. The first non-invasive external VNS device was cleared by the FDA for the treatment of cluster headaches and migraines in 2017.
- Conditions
- Post-Treatment Lyme Disease
- Being tested
- taVNS
- Keywords
- Lyme Disease, Vagus Nerve Stimulation, taVNS, Fatigue, Post-Treatment Lyme Disease
- Medical subject headings
- Post-Lyme Disease Syndrome, Lyme Disease, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
taVNSDevice
Includes the use of Soterix Medical Device, which consists of a handheld "smart-phone" size device. There are two electrodes (designed for studies in infants) with small patches that the participant places on the external ear (the cymbals conchae and the tragus). The stimulation intensity is personalized for each participant based on perceptual threshold.
| Study group | Role | What they receive |
|---|---|---|
| PTLD - active taVNS | Experimental | Participants with Post-treatment Lyme Disease (PTLD) will start with 40 sessions (i.e., 4 weeks of Monday to Friday, twice daily treatments that last 1 hour each session) to receive transcutaneous auricular Vagus Nerve Stimulation (taVNS). If compliance is less than 70% in the open label treated participants, then the investigators will modify the treatment design accordingly. Receives: Device: taVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment Rate
To assess feasibility of conducting a study of taVNS for patients with persistent symptoms after Lyme disease, recruitment will be calculated from the number of participants in the study.
Measured: Up to 4 weeks
Compliance Rate
To assess feasibility of taVNS for patients with persistent symptoms after Lyme disease, compliance will be measured as the number of completed sessions per participant.
Measured: Up to 4 weeks
Drop-out Rate
To assess tolerance to taVNS, the drop-out rate will be calculated from the number of participants who discontinue from the study.
Measured: Up to 4 weeks
Ratings of Treatment Satisfaction (Likert Scale)
To assess tolerance to taVNS, participants will be asked to rate their satisfaction with the treatment experience on a Likert Scale, with 1 (min) indicating "very dissatisfied" to 5 (max), indicating "very satisfied". A higher score indicates a better outcome.
Measured: Up to 4 weeks
Total Number of Treatment Emergent Adverse Events
To assess safety of taVNS, the total number of treatment emergent adverse events will be assessed using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) tool.
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start8 May 2023
- Primary completionNov 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Treatment Lyme DiseaseStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian A Fallon, Columbia University
- Investigators
- Brian A. Fallon, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05776251
- Sponsor's protocol ID
- AAAV3947
- Status last verified
- May 2026
- First submitted
- 8 Mar 2023
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for Persistent Symptoms From Lyme Disease: a Feasibility, Tolerability, and Safety Study
- ClinicalTrials.gov ID
- NCT05776251
- Acronym / sponsor ID
- AAAV3947
- Conditions
- Post-Treatment Lyme Disease
- Keywords
- Lyme Disease, Vagus Nerve Stimulation, taVNS, Fatigue, Post-Treatment Lyme Disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 8 May 2023 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 20 Mar 2023 (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.
This study is one of the first studies to investigate a non-antibiotic approach to the treatment of symptoms that persist after antibiotic treatment for Lyme disease (PTLS). Transcutaneous auricular vagus nerve stimulation (taVNS) offers the potential of being an effective and non-toxic approach to reduce the burden of multisystem symptoms in patients with PTLS. This study seeks to address an important goal: to assess the safety, feasibility, and tolerability of a new non-invasive, non-pharmacologic treatment for patients with symptoms that persist despite prior antibiotic treatment for Lyme disease.
Detailed description
Musculoskeletal pain, fatigue, and cognitive and mood problems are common persistent disabling symptoms among individuals with post-treatment Lyme Disease. Each year in the United States, approximately 476,000 individuals are newly diagnosed with Lyme disease and 10-20% of these go on to have persistent or relapsing symptoms that are not responding to the current best antibiotic therapies.
Individuals with persistent infection are likely to respond best to additional antibiotic therapy. Individuals with post- infectious causes require other approaches - such as ones that impact ongoing inflammation or altered neural circuits and metabolism. Safe and effective treatment for these individuals with persistent symptoms represents a prominent unmet need.
Vagus nerve stimulation (VNS) may be a treatment with considerable impact for patients with post-treatment Lyme disease. The vagus nerve (the 10th and longest cranial nerve) impacts the central nervous system, the autonomic nervous system (e.g, heart, lungs, digestive tract), and the systemic inflammatory response. It has also been shown to play a role in cognition, pain, mood disorders, inflammation, and immune function. Research over the last 2 decades has demonstrated that electrical stimulation of the vagus nerve can have multiple salutary effects in both animal models of disease and human illness. Until very recently, VNS has been considered an invasive intervention, reserved for patients with refractory disease, as it requires surgery to implant the device; this approach is costly and puts patients at risk of infection and other complications. These factors have limited the accessibility and broad application of VNS. A non-invasive approach to VNS would increase affordability, accessibility, and decrease risk. This is now possible. The first non-invasive external VNS device was cleared by the FDA for the treatment of cluster headaches and migraines in 2017.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PTLD - active taVNS | Experimental | Device: taVNSParticipants with Post-treatment Lyme Disease (PTLD) will start with 40 sessions (i.e., 4 weeks of Monday to Friday, twice daily treatments that last 1 hour each session) to receive transcutaneous auricular Vagus Nerve Stimulation (taVNS). If compliance is less than 70% in the open label treated participants, then the investigators will modify the treatment design accordingly. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- History of either Definite or Highly Probable Past Lyme disease diagnosed and treated by a health care provider more than 6 months previously.
- Have one or more current symptoms attributed to Lyme disease that were also present during the initial 6-month period after diagnosis and antibiotic treatment of Lyme disease.
- Individuals reporting that current symptoms cause clinically significant distress or impairment in functioning.
- Previously treated for Lyme disease with at least two courses of antibiotics considered appropriate for Lyme disease.
- Individuals who agree to not start a new medical or psychiatric treatment (that might impact study outcomes) for their chronic symptoms during the course of this study (unless deemed necessary by their primary care physician (PCP)).
Key exclusion criteria (14 listed)
- Current or past history of cardiovascular disorder(s) (coronary artery disease, peripheral artery disease, stroke, aortic disease, or other major cardiac condition). A history within the last year of unexplained fainting spells or of vasovagal syncope or feeling faint in response to medical settings or pain. Symptomatic bradycardia, orthostatic (postural) hypotension not correctable by fluid intake (i.e., a drop of >20 mm Hg systolic, 10 mm Hg diastolic or both), or persistent hypotension (BP below 90 mmHg systolic).
- Abnormal EKG findings (e.g., significant bradycardia) considered significant by a cardiologist.
- A diagnosed current major central nervous system disease (e.g., multiple sclerosis (MS), epilepsy, neurodegenerative diseases, ischemic stroke, Parkinson's, traumatic brain injury with cognitive impairment, etc.) or a history of brain surgery or brain tumors.
- A current psychiatric disorder that might impact treatment compliance (e.g., bipolar disorder, psychosis, substance abuse).
- Suicidal ideation with method, plan or intent in the last 6 months or a lifetime history of suicidal behavior.
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 |
|---|---|---|
| taVNSIncludes the use of Soterix Medical Device, which consists of a handheld "smart-phone" size device. There are two electrodes (designed for studies in infants) with small patches that the participant places on the external ear (the cymbals conchae and the tragus). The stimulation intensity is personalized for each participant based on perceptual threshold. | Device | PTLD - active taVNS |
Primary outcome
Recruitment Rate
Time frame: Up to 4 weeks
To assess feasibility of conducting a study of taVNS for patients with persistent symptoms after Lyme disease, recruitment will be calculated from the number of participants in the study.
Compliance Rate
Time frame: Up to 4 weeks
To assess feasibility of taVNS for patients with persistent symptoms after Lyme disease, compliance will be measured as the number of completed sessions per participant.
Drop-out Rate
Time frame: Up to 4 weeks
To assess tolerance to taVNS, the drop-out rate will be calculated from the number of participants who discontinue from the study.
Ratings of Treatment Satisfaction (Likert Scale)
Time frame: Up to 4 weeks
To assess tolerance to taVNS, participants will be asked to rate their satisfaction with the treatment experience on a Likert Scale, with 1 (min) indicating "very dissatisfied" to 5 (max), indicating "very satisfied". A higher score indicates a better outcome.
Total Number of Treatment Emergent Adverse Events
Time frame: Up to 4 weeks
To assess safety of taVNS, the total number of treatment emergent adverse events will be assessed using the Systematic Assessment for Treatment Emergent Effects (SAFTEE) tool.
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 6 May 2026.
- Homepage for Columbia University's Lyme and Tick-Borne Diseases Research CenterLink provided by the sponsor.
- Homepage for the Lyme Clinical Trials NetworkLink provided by the sponsor.
- First Step webpage for eligibility assessment for taVNS StudyLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Brian A. Fallon, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing taVNS in people with Post-Treatment Lyme Disease, run by Columbia University 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 12 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 6 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 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 Brian A. Fallon, MD (646-774-7503, baf1@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment Rate (time frame: Up to 4 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2026.