taVNS for Persistent Symptoms From Lyme Disease

Inclusion Criteria:

• History of either Definite or Highly Probable Past Lyme disease diagnosed andtreated by a health care provider more than 6 months previously.

• Have one or more current symptoms attributed to Lyme disease that were also presentduring the initial 6-month period after diagnosis and antibiotic treatment of Lymedisease.

• Individuals reporting that current symptoms cause clinically significant distress orimpairment in functioning.

• Previously treated for Lyme disease with at least two courses of antibioticsconsidered appropriate for Lyme disease.

• Individuals who agree to not start a new medical or psychiatric treatment (thatmight impact study outcomes) for their chronic symptoms during the course of thisstudy (unless deemed necessary by their primary care physician (PCP)).

• Individuals whose current treatment (that might impact study outcomes) has beenstable for at least 6 weeks prior to baseline visit.

• 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 3-5study visits.

• Willingness to have a 12-lead electrocardiogram (EKG) when evaluated on site and, ifan EKG was conducted in the past year, willingness to try to obtain that EKG for usto 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 sessionsthat will be monitored during work hours (8 am to 6 pm).

Exclusion Criteria:

• Current or past history of cardiovascular disorder(s) (coronary artery disease,peripheral artery disease, stroke, aortic disease, or other major cardiaccondition). A history within the last year of unexplained fainting spells or ofvasovagal syncope or feeling faint in response to medical settings or pain.Symptomatic bradycardia, orthostatic (postural) hypotension not correctable by fluidintake (i.e., a drop of >20 mm Hg systolic, 10 mm Hg diastolic or both), orpersistent hypotension (BP below 90 mmHg systolic).

• Abnormal EKG findings (e.g., significant bradycardia) considered significant by acardiologist.

• A diagnosed current major central nervous system disease (e.g., multiple sclerosis (MS), epilepsy, neurodegenerative diseases, ischemic stroke, Parkinson's, traumaticbrain injury with cognitive impairment, etc.) or a history of brain surgery or braintumors.

• A current psychiatric disorder that might impact treatment compliance (e.g., bipolardisorder, psychosis, substance abuse).

• Suicidal ideation with method, plan or intent in the last 6 months or a lifetimehistory of suicidal behavior.

• Current moderate-severe or severe depression (score of 15 and higher) on the PatientHealth Questionnaire-8 (PHQ-8) at screening.

• Current serious unstable medical illness.

• Currently taking opiate-based medication or have taken antibiotics in the last 6weeks for tick-borne illness.

• Ear-related: a) facial or ear pain; b) recent ear trauma; c) damage to left or rightear or anatomy that does not allow taVNS; d) ear infection (otitis media orexterna); e) scar or inflammation on ear; f) Cochlear implants.

• Currently or recently (within 6 months) in a clinical trial of an investigationalmedicinal product or another medical device.

• Females who are pregnant or planning to become pregnant during the course of thisstudy.

• 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 theneck.

• Individuals who have had surgery to cut the vagus nerve in the neck (cervicalvagotomy).