Augmenting Standard-of-care Treatment of Plaque Psoriasis by Neuromodulation

The human body responds to inflammation, such as psoriatic skin lesions, by activating the cholinergic anti-inflammatory pathway. In patients with plaque psoriasis, this pathway is not sufficient to clear the skin lesions. Importantly, the vagus nerve, that is part of the anti-inflammatory pathway, also innervates the ear where it can be activated through non-invasive transcutaneous auricular vagus nerve stimulation (taVNS). This raises the research question if taVNS - added to standard of care - improves the symptoms of plaque psoriasis by augmenting the function of the cholinergic anti-inflammatory pathway. Thus, the aim of this project is to test the hypothesis that daily taVNS applied for 3 months results in anti-inflammatory actions and improvements in the Psoriasis Area and Severity Index (PASI). Potential anti-inflammatory actions of taVNS compared to a sham-taVNS control group will be assessed by plasma cytokine levels, flow cytometry, and cell culture experiments. This project is potentially significant, because it may demonstrate that taVNS lessens the symptoms of plaque psoriasis and, therefore, improves the quality of life of millions of patients.

Study Overview

• Status: Recruiting
• Conditions: Psoriasis Vulgaris
• Intervention / Treatment: Device: Active taVNS; Device: Sham taVNS

Detailed Description

An estimated 20% of psoriasis patients experience treatment failure. Afferent vagal nerve fibers that are part of the anti-inflammatory reflex sense inflammation, such as psoriatic skin lesions. The investigators' pilot data show that transcutaneous auricular vagus nerve stimulation (taVNS) activates afferent nerve fibers within the auricular branch of the vagus nerve to trigger anti-inflammatory reflex responses in healthy individuals. However, it is unknown if taVNS improves plaque psoriasis through the anti-inflammatory reflex. The lack of studies on taVNS in plaque psoriasis constitutes a missed opportunity to reduce treatment failures.

The long-term goal of this research is to establish a neuromodulatory approach to activate the anti-inflammatory reflex in patients with plaque psoriasis to lessen treatment failures. The objective of this study is to test the hypothesis that taVNS elicits anti-inflammatory reflex responses and reduces the severity of plaque psoriasis.

In a single-blinded randomized controlled clinical trial, participants will self-administer taVNS or sham-taVNS (control) daily for a duration of 3 months, while continuing their standard-of-care treatment. At baseline, 7 days, and 1, 2, and 3 months, clinical , autonomic, and inflammatory responses will be assessed.

At the conclusion of this study, the investigators expect to demonstrate anti-inflammatory reflex responses to taVNS and reduced severity of plaque psoriasis. These outcomes are expected to have important positive impact, because they are anticipated to reduce treatment failures in patients with plaque psoriasis.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Harald M Stauss, MD, PhD; Phone Number: 575-674-2327; Email: hstauss@burrell.edu

Study Locations

• United States
  • New Mexico
    • Las Cruces, New Mexico, United States, 88001
      • Recruiting
      • Burrell College of Osteopathic Medicine
      • Contact: Harald M Stauss, MD, PhD; Phone Number: 575-674-2327; Email: hstauss@bcomnm.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older
• Plaque psoriasis diagnosed by a dermatologist

Exclusion Criteria:

• pregnancy
• vestibulocochlear neuronitis or nerve damage
• cardiac arrhythmia
• epilepsy
• anticipated change in medication during the 3-month study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active taVNS; These patients will self-administer transcutaneous auricular vagus nerve stimulation (taVNS).	Device: Active taVNS; A bipolar clip electrode is placed at the cymba conchae of the ear. Through this bipolar clip electrode, afferent nerve fibers within the auricular branch of the vagus nerve will be stimulated. Subjects self-administer the stimulation on a daily basis for 3 months.; Other Names: active transcutaneous auricular vagus nerve stimulation
Sham Comparator: Sham taVNS; These patients will self-administer a sham procedure mimicking the active taVNS procedure.	Device: Sham taVNS; A bipolar clip electrode is placed at the cymba conchae of the ear. However, active stimulation of the afferent nerve fibers within the auricular branch of the vagus nerve will not occur, because the electrode wire is electrically interrupted. Subjects self-administer the sham taVNS on a daily basis for 3 months.; Other Names: sham transcutaneous auricular vagus nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Psoriasis Area and Severity Index from Baseline at 1 Week	Clinical assessment of the severity of plaque psoriasis	After 1 week of treatment.
Change in Psoriasis Area and Severity Index from Baseline at 1 Month	Clinical assessment of the severity of plaque psoriasis	After 1 month of treatment.
Change in Psoriasis Area and Severity Index from Baseline at 2 Months	Clinical assessment of the severity of plaque psoriasis	After 2 months of treatment.
Change in Psoriasis Area and Severity Index from Baseline at 3 Months	Clinical assessment of the severity of plaque psoriasis	After 3 months of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Heart Rate Variability from Baseline at 1 Week	Heart rate variability will be determined from ECG recordings	After 1 week of treatment.
Change in Heart Rate Variability from Baseline at 1 Month	Heart rate variability will be determined from ECG recordings	After 1 month of treatment.
Change in Heart Rate Variability from Baseline at 2 Months	Heart rate variability will be determined from ECG recordings	After 2 months of treatment.
Change in Heart Rate Variability from Baseline at 3 Months	Heart rate variability will be determined from ECG recordings	After 3 months of treatment.
Change in Plasma Cytokine Levels from Baseline at 1 Week	Plasma concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be determined from blood samples.	After 1 week of treatment.
Change in Plasma Cytokine Levels from Baseline at 1 Month	Plasma concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be determined from blood samples.	After 1 month of treatment.
Change in Plasma Cytokine Levels from Baseline at 2 Months	Plasma concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be determined from blood samples.	After 2 months of treatment.
Change in Plasma Cytokine Levels from Baseline at 3 Months	Plasma concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be determined from blood samples.	After 3 months of treatment.
Change from baseline in cytokine release from cultured leukocytes at 1 week	Cytokine concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be measured in supernatant from LPS-stimulated leukocyte cultures.	After 1 week of treatment.
Change from baseline in cytokine release from cultured leukocytes at 1 month	Cytokine concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be measured in supernatant from LPS-stimulated leukocyte cultures.	After 1 month of treatment.
Change from baseline in cytokine release from cultured leukocytes at 2 months	Cytokine concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be measured in supernatant from LPS-stimulated leukocyte cultures.	After 2 months of treatment.
Change from baseline in cytokine release from cultured leukocytes at 3 months	Cytokine concentrations (pg/mL) for 8 different cytokines (GM CSF, IFN-γ, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α) will be measured in supernatant from LPS-stimulated leukocyte cultures.	After 3 months of treatment.

Collaborators and Investigators

• Sponsor: Burrell College of Osteopathic Medicine
• Investigators: Principal Investigator: Harald M Stauss, MD, PhD, Burrell College of Osteopathic Medicine

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: February 4, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: transcutaneous auricular vagus nerve stimulation; inflammation
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: 0090_2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No