Image courtesy of Mara Kuvaldina, PhD
Lyme disease is a complex infection that starts with flu-like symptoms but can progress through later stages to impact the heart, nervous system, and joints. Many cases of Lyme disease clear up if diagnosed and treated immediately, but some 10-20% of patients go on to experience persistent symptoms. “These patients are suffering and their quality of life is poor,” says Dr. Brian Fallon, Director of the Lyme and Tick-Borne Diseases Research Center at Columbia University Irving Medical Center. Key symptoms plaguing these patients include fatigue, musculoskeletal and neuropathic pain, and cognitive problems. These patients are looking for relief, and a new study by Dr. Fallon’s team is exploring vagus nerve stimulation as a potential approach for persistent symptoms.
The study involves transcutaneous auricular vagus nerve stimulation (taVNS), which means mild electrical pulses are applied to the outer ear to stimulate the vagus nerve. Some studies in autoimmune and inflammatory conditions suggest that vagus nerve stimulation may help reduce pain and fatigue. Selected VNS devices are FDA-approved for epilepsy, rheumatoid arthritis, and treatment-resistant depression, with certain non-invasive devices also cleared for migraine and cluster headache. Other uses remain under investigation. “Recent studies suggest that vagus nerve stimulation may have beneficial effects on mood, and may also influence sleep and cognition, though evidence in these areas is still emerging,” says Dr. Fallon. “These are the research findings that made me eager to launch a study of vagus nerve stimulation for people with long Lyme.”
The vagus nerve is the longest cranial nerve in the body, extending from the brainstem through the neck, thorax, and abdomen. Dr. Fallon explains that from the brainstem emerge two vagus nerve bundles. “Each bundle contains about 100,000 nerve fibers that serve as bidirectional communication highways between the body and brain, innervating most of our major internal organs including the heart, lungs, intestines, spleen, and liver.” He explains that the vagus nerve plays a major role in the autonomic nervous system and also contributes to immune regulation by modulating inflammatory responses.
While we don’t yet know exactly, we do know that the Lyme disease bacteria, Borrelia burgdorferi, can lead to cranial nerve dysfunction, most commonly affecting the facial nerve, though involvement of other cranial nerves is less well characterized.
Vagus nerve stimulation uses tiny electrical pulses. In the past, this required surgical implantation of a device right on the nerve. Newer, non-invasive devices target branches of the vagus nerve on the surface of the outer ear or along the neck. The Columbia study involves a small hand-held device about the size of a cell phone that provides the stimulation to the outer surface of the ear at two different locations that are known to contain branches of the auricular vagus nerve.
The Columbia Clinical Trials study, led by Dr. Fallon and his team, is a trial involving four weeks of at-home treatment with a cell-phone sized device and a wire that extends to a patch on your ear, Monday-Friday, twice daily, for an hour at a time. “Everybody gets active stimulation, personalized based on comfort,” Dr. Fallon says. “People might experience a slight tingling during stimulation but often this becomes imperceptible during the treatment.” He notes that “a large systematic review in 2018 of all prior published studies concluded that transcutaneous vagus nerve stimulation is generally safe and well-tolerated, with the most common side effect being local skin discomfort during ear stimulation in about 18% of patients.”
In addition to the at-home treatment, the study requires three in-person visits to Columbia. The first is to confirm eligibility and the second and third are to conduct assessment and training. Blood samples will be collected before and after treatment.
The study is open to people ages 18-65 with a well-documented history of Lyme disease and persistent fatigue. The study is nearing completion, but the researchers hope to enroll another 12 people over the next six months.
“Because this is the first study of vagus nerve stimulation for long Lyme, we have much to learn,” says Dr. Fallon. Questions the researchers hope to answer are: Will people be able to allocate time for 1 hour twice-daily for the stimulation sessions? Could taVNS offer similar therapeutic effects in long Lyme patients as VNS has shown in other conditions? Which symptom profiles change and which self-report measures would be most sensitive in detecting change?
Dr. Fallon explains, “Because this pilot study is small in size and not sham-controlled, we cannot test efficacy; some people may get better by chance or due to the typical waxing and waning of symptoms.” Blood samples collected before and after treatment will be used to assess whether there are markers associated with clinical response or with change over time. These biomarkers, if found and validated as predictors of response, would be important for clinical care, as clinicians may then be able to recommend this treatment to people who are more likely to benefit – a goal of personalized medicine.
People who are between 18-65 with a well-documented history of Lyme disease and persistent fatigue are encouraged to apply. See the study recruitment page to learn more.
During the four weeks, the study coordinator and physicians monitor patient progress remotely and are available for any questions.
Ongoing research into the chronic manifestations of Lyme disease is crucial to improving patient outcomes. Though the taVNS study is a pilot clinical study, participants will help contribute to public health knowledge about vagus nerve stimulation and Lyme disease. Study participants will receive a $250 stipend for completing the four-week study.
Global Lyme Alliance (GLA) helped establish the Columbia Lyme and Tick-Borne Diseases Research Center in partnership with the Lyme Disease Association. GLA’s early funding supported the development of essential infrastructure, laying the groundwork for research. With significant later support from the Steven and Alexandra Cohen Foundation, the center was able to launch pilot studies and advance clinical research into treatments for those with persistent symptoms following Lyme disease. This collective support has helped make ongoing clinical trials, like those highlighted in this series, possible.
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