Effect of Auricular Vagal Nerve Electrical Stimulation on Post-Treatment Lyme Disease Syndrome

NCT04938687 | Completed Results

• 1 other identifier: 2021P000566
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is to assess if respiratory-gated auricular vagal nerve stimulation (RAVANS) can improve symptoms of post-treatment Lyme disease syndrome

Conditions

Post-Treatment Lyme Disease Syndrome

Outcome Measures

Primary Outcomes (1)

• Horowitz Lyme-Multiple Systemic Infectious Disease Syndrome Questionnaire

  This 55-item questionnaire evaluates the frequency, severity, and incidence of Lyme symptoms as well as assessing one's perceived overall health. Minimum value:0 Maximum value: 114 The higher number indicates more symptoms

  Before treatment (baseline) and Post treatment ( at the end of 2-week treatment)

Secondary Outcomes (12)

• Sedentary Behaviors Questionnaire

  Before treatment (baseline) and Post treatment (at the end of 2-week treatment)

• Fatigue Symptom Inventory

  Before treatment (baseline) and Post treatment (at the end of 2-week treatment)

• Brief Pain Inventory-Pain 24 Hours

  Before treatment (baseline) and Post treatment (at the end of 2-week treatment)

• Beck Depression Inventory

  Before treatment (baseline) and Post treatment (at the end of 2-week treatment)

• Beck Anxiety Inventory

  Before treatment (at baseline) and after treatment (at the end of 2-week treatment)

Study Arms (2)

RAVANS

EXPERIMENTAL

active RAVANS, 20 minutes each treatment, 3 times per week for 2 weeks

Device: respiratory-gated auricular vagal afferent nerve stimulation (RAVANS)

Sham stimulation

SHAM COMPARATOR

Sham-stimulation, 20 minutes each treatment, 3 times per week for 2 weeks

Device: Sham RAVANS

Interventions

respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) DEVICE

non-painful electrical stimulation of the auricle

Also known as: transcutaneous vagus nerve stimulation

RAVANS

Sham RAVANS DEVICE

sham stimulation

Sham stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults of all genders ≥ 18 years
• History of Lyme disease treated with antibiotics, and current PTLDS diagnosed by a physician
• Evidence of past B. burgdorferi infection based on positive results from both enzyme immunoassay and Western blot testing.
• Ability to provide informed consent,
• willing to maintain current PTLDS treatment regimen during participation in the study (if on long-term antibiotics or supplements for PTLDS management).

You may not qualify if:

• History of other neurological disorder that in the judgement of the investigator could interfere with the treatment or the interpretation of the results (e.g., epilepsy, history of stroke, tumor, brain tissue damaging pathologies etc.).
• Current psychotic disorder (e.g., schizophrenia).
• Current acute illness or infection (e.g. cold or flu).
• History of recurrent vaso-vagal syncope
• Bradycardia defined as resting heart rate \<50bpm
• Implanted electronic device (e.g., pacemaker, neurostimulator)
• Use of immunosuppressive medication such as prednisone, TNF medications within 2 weeks of the visit or anticipated use during the study.
• Current use of anti-inflammatory steroid use.
• Pregnancy

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead

Related Publications (9)

• Aranow C, Atish-Fregoso Y, Lesser M, Mackay M, Anderson E, Chavan S, Zanos TP, Datta-Chaudhuri T, Bouton C, Tracey KJ, Diamond B. Transcutaneous auricular vagus nerve stimulation reduces pain and fatigue in patients with systemic lupus erythematosus: a randomised, double-blind, sham-controlled pilot trial. Ann Rheum Dis. 2021 Feb;80(2):203-208. doi: 10.1136/annrheumdis-2020-217872. Epub 2020 Nov 3.

  PMID: 33144299 BACKGROUND

• Dantzer R, Konsman JP, Bluthe RM, Kelley KW. Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent? Auton Neurosci. 2000 Dec 20;85(1-3):60-5. doi: 10.1016/S1566-0702(00)00220-4.

  PMID: 11189027 BACKGROUND

• Ek M, Kurosawa M, Lundeberg T, Ericsson A. Activation of vagal afferents after intravenous injection of interleukin-1beta: role of endogenous prostaglandins. J Neurosci. 1998 Nov 15;18(22):9471-9. doi: 10.1523/JNEUROSCI.18-22-09471.1998.

  PMID: 9801384 BACKGROUND

• Embers ME, Hasenkampf NR, Jacobs MB, Tardo AC, Doyle-Meyers LA, Philipp MT, Hodzic E. Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding. PLoS One. 2017 Dec 13;12(12):e0189071. doi: 10.1371/journal.pone.0189071. eCollection 2017.

  PMID: 29236732 BACKGROUND

• Garcia RG, Lin RL, Lee J, Kim J, Barbieri R, Sclocco R, Wasan AD, Edwards RR, Rosen BR, Hadjikhani N, Napadow V. Modulation of brainstem activity and connectivity by respiratory-gated auricular vagal afferent nerve stimulation in migraine patients. Pain. 2017 Aug;158(8):1461-1472. doi: 10.1097/j.pain.0000000000000930.

  PMID: 28541256 BACKGROUND

• Kong J, Fang J, Park J, Li S, Rong P. Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives. Front Psychiatry. 2018 Feb 5;9:20. doi: 10.3389/fpsyt.2018.00020. eCollection 2018.

  PMID: 29459836 BACKGROUND

• Napadow V, Edwards RR, Cahalan CM, Mensing G, Greenbaum S, Valovska A, Li A, Kim J, Maeda Y, Park K, Wasan AD. Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation. Pain Med. 2012 Jun;13(6):777-89. doi: 10.1111/j.1526-4637.2012.01385.x. Epub 2012 May 8.

  PMID: 22568773 BACKGROUND

• VanElzakker MB. Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis. Med Hypotheses. 2013 Sep;81(3):414-23. doi: 10.1016/j.mehy.2013.05.034. Epub 2013 Jun 19.

  PMID: 23790471 BACKGROUND

• Zubcevik N, Mao C, Wang QM, Bose EL, Octavien RN, Crandell D, Wood LJ. Symptom Clusters and Functional Impairment in Individuals Treated for Lyme Borreliosis. Front Med (Lausanne). 2020 Aug 21;7:464. doi: 10.3389/fmed.2020.00464. eCollection 2020.

  PMID: 32974369 BACKGROUND

MeSH Terms

Conditions

Post-Lyme Disease Syndrome

Condition Hierarchy (Ancestors)

Lyme Disease; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Borrelia Infections; Spirochaetales Infections; Tick-Borne Diseases; Vector Borne Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Qing Mei Wang, MD, PhD
• Organization: Spaulding Rehabilitation Hospital

wang.qingmei@mgh.harvard.edu

(617) 952-5299

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Stroke Biological Recovery Laboratory

Model Details: randomized, double blinded, sham-controlled

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 24, 2021
• Study Start: May 31, 2022
• Primary Completion: August 11, 2024
• Study Completion: April 25, 2025
• Last Updated: February 12, 2026
• Results First Posted: November 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share