Transcutaneous Vagus Nerve Stimulation in SLE (TvSSLE)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect many parts of the body, including the joints and muscles, leading to persistent pain and fatigue. Even when the disease is relatively well-controlled, these symptoms can significantly impact a person’s quality of life. Traditional medications used in lupus often suppress the immune system, which can cause serious side effects. There is an urgent need to develop new ways to manage lupus-related pain and fatigue without the risks of immunosuppressive drugs. Dr. Aranow will conduct a trial to evaluate the effects and durability of an innovative approach —stimulating the vagus nerve— as a potential way to treat pain and fatigue in lupus. This could provide a revolutionary, drug-free option for patients who struggle with persistent symptoms.

A key player in the body’s communication system, the vagus nerve is a highway that carries information to and from the brain to various internal organs like the heart, lungs, and digestive system. It plays a role in regulating inflammation, heart rate, and digestion, and research shows that stimulating the vagus nerve can help treat conditions like epilepsy, depression, and migraines. Dr. Aranow will assess the effects of vagus nerve stimulation on pain and fatigue using a device on the skin just outside the ear, where a branch of the vagus nerve is located. 18 people with SLE will receive non-painful vagus nerve stimulation for 5 minutes a day for 28 days, and the change in pain from baseline (before treatment) to day 29 will be assessed. Participants will then be monitored for an additional 28 days without stimulation to determine if the benefits last after stopping the treatment. Dr. Aranow will also explore potential mechanisms by which vagus nerve stimulation reduces pain and fatigue.

What this means for people with lupus

This innovative approach could offer a safe, non-invasive option to relieve pain and fatigue, which are among the most challenging symptoms of lupus. With promising early results and limited treatment options currently available for these symptoms, Dr. Aranow’s approach has the potential to make a significant difference in the lives of people with lupus.

Musculoskeletal (MS) pain and fatigue are common symptoms of patients with Systemic Lupus Erythematosus (SLE) affecting up to 95% and contributing to a reduced quality of life. Safe and efficacious treatment remains an unmet need for these disease manifestations. Stimulation of the vagus nerve results in beneficial effects in patients. We recently completed a short, small scale, randomized, sham-controlled, double blind clinical trial of transauricular vagus nerve stimulation (taVNS) in patients with SLE. The clinical benefit on MS pain and fatigue was dramatic. We now propose a randomized sham controlled clinical trial assessing the efficacy and durability of a longer exposure to taVNS (28 days in comparison to the 4 day exposure in the previous trial) in patients with MS pain. In this clinical trial we will also explore potential biologic mechanisms and pathways by which taVNS exerts ifs effects in SLE, including potential effects on gut permeability and the microbiome. This study proposes a randomized, double-blind, sham controlled clinical trial to evaluate transcutaneous, noninvasive stimulation of the vagus nerve through its auricular branch (taVNS) in patients with SLE and MS pain. We will randomize 18 SLE patients with MS pain = 4 on an anchored 10cm Visual Analog Scale for pain and MS activity defined by SLEDAI-2K arthritis or a BILAG MS score = C to receive taVNS or sham stimulation (SS), 2:1. Both subjects and the evaluating investigator will be blind to the treatment allocation. Subjects will receive 5 minutes of stimulation daily for 28 days and will be followed off treatment for 28 days. The primary endpoint is the change in pain from baseline to day 29, using a within subject analysis; durability will be examined through day 59. Safety will be monitored throughout the trial by assessments of adverse events. Subjects will complete weekly evaluations assessing pain, pain intensity, pain interference and fatigue. Disease activity (SLEDAI-2K, BILAG 2004, Physician Global Assessment (PGA), cutaneous activity (CLASI) and tender and swollen joint counts) and patient assessments of quality of life, and global assessment of disease (PtGA) will be captured at baseline, day 28 and day 56. Determination of subjects achieving a SRI-4 (SLE Response Index-4) or LLDAS (Low Lupus Disease Activity State) will additionally be assessed at days 29 and 57. Potential mechanisms of taVNS will be explored and will include evaluation of neuropeptides, neurotrophins, tryptophan pathway metabolites, immunometabolomics as well as analyses of gut permeability and stool microbiome. We have identified an industrial partner for future collaborations, who is interested in commercializing this therapeutic approach to reduce pain and fatigue in SLE. Documentation needed to support a future submission for regulatory approval will be transferred to this partner.