Modelling and Control of Non-invasive Vagus Nerve Stimulation for Autoimmune Diseases (1A)

NCT05704153 | Recruiting FDA Device

• 1 other identifier: PID2020-117171RA-I00-1A
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this clinical trial is to evaluate the causality relationship between the non vagus nerve stimulation waveform parameters and the therapeutic effect. Thus, unlocking a pathway to optimize parameters that maximize the benefits of therapy and minimize unwanted side effects. The experimental design includes the analysis of physiological signals, clinical biomarkers of disease, and clinical outcomes to determine the most effective measures for the monitoring, optimization, and personalization of non vagus nerve stimulation in systemic lupus erythematosus disease.

Conditions

Systemic Lupus Erythematosus; Autoimmune Disorder; Vagus Nerve Autonomic Disorder

Keywords

Parasympathetic Nervous System; Vagus Nerve Stimulation

Outcome Measures

Primary Outcomes (1)

• Number of patients with Systemic Lupus Erythematosus with clinical and analytic change after non-invasive vagus nerve stimulation (nVNS) at different waveform parameters

  We will develop an nVNS platform with an integrated nVNS decision support system, including nVNS and physiological wearable sensors, that will optimize nVNS waveform parameters to maximize the therapeutic effect while minimizing unwanted side effects. Therapeutic effect and side effects will be measured by clinical, neurophysiological and analytic tests as described in "secondary outcome measures".

  Visit 1(baseline, exploratory study, up to 30days prior to first nVNS)

Secondary Outcomes (27)

• Blood count

  Baseline, after five days of stimulation and 1 month after stimulation. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels

• Erythrocyte sedimentation rate

  Baseline, after five days of stimulation and 1 month after stimulation. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels

• C-reactive protein

  Baseline, after five days of stimulation and 1 month after stimulation. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels

• Anti-dsDNA

  Baseline, after five days of stimulation and 1 month after stimulation. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels

• C3, C4

  Baseline, after five days of stimulation and 1 month after stimulation. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels

Study Arms (3)

Sham

SHAM COMPARATOR

Control group to be subjected to sham stimulation.

Device: Sham Intervention

30 hertz (Hz) Stimulation

EXPERIMENTAL

Group of patients treated via 30Hz transcutaneous electrical nerve stimulation

Device: Parasym 30Hz

1Hz Stimulation

EXPERIMENTAL

Group of patients treated via 1Hz transcutaneous electrical nerve stimulation

Device: Parasym 1Hz

Interventions

Parasym 1Hz DEVICE

Transcutaneous auricular vagus nerve stimulation of 1Hz

1Hz Stimulation

Parasym 30Hz DEVICE

Transcutaneous Auricular Vagus Nerve Stimulation of 30Hz

30 hertz (Hz) Stimulation

Sham Intervention DEVICE

Sham stimulation

Sham

Eligibility Criteria

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

You may qualify if:

• Systemic lupus erythematosus (SLE) (defined by the American College of Rheumatology- or SLICC criteria)
• Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale
• BILAG C on Musculoskeletal Domain of the BILAG 2004
• If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone or equivalent) for at least 28 days before baseline,
• If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline
• Able and willing to give written informed consent and comply with the requirements of the study protocol.

You may not qualify if:

• Treatment with rituximab within one year of baseline as it is related to lymphocyte depletion that could alter the result of the biomarker study (subjects with previous treatment with rituximab can enter study only with documentation of B cell repletion).
• Treatment with cyclophosphamide within 2 months of baseline as it is related to lymphocyte depletion that could alter the result of the biomarker study.
• Expectation to increase steroids and/or immunosuppressive treatment.
• Anti-phospholipid syndrome.
• Fibromyalgia (fibromyalgia will be defined as a score \> 13 on the Fibromyalgia Symptom Scale), chronic fatigue syndrome.
• Treatment with an anti-cholinergic or sympathicomimetic medication, including over the counter medications.
• Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
• Joint replacement within 60 days prior to study enrolment or planned within the course of the study.
• Any planned surgical procedure requiring general anaesthesia within the course of the study.
• Intra-articular cortisone injections within 28 days of the start of study.
• Chronic inflammatory disorders apart from SLE affecting the joints.
• Investigational drug and/or treatment during the 28 days or seven half-lives of the investigational drug prior to the start of study drug dosing (Day 0), whichever is the greater length of time.
• Active infection including hepatitis B, hepatitis C or HIV at baseline due to high prevalence of neuropathy.
• Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention.
• Pregnancy or lactation.

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• Universitat de Girona: collaborator
• Hospital Mutua de Terrassa: collaborator
• Imperial College London: collaborator
• Johns Hopkins University: collaborator

Study Sites (1)

Hospital Clinic

Barcelona, 08036, Spain

RECRUITING

Related Publications (1)

• Contreras I, Navarro-Otano J, Rodriguez-Pinto I, Guemes A, Alves E, Rios-Garces R, Espinosa G, Alejaldre A, Beneyto A, Ramkissoon CM, Vehi J, Cervera R. Optimizing Noninvasive Vagus Nerve Stimulation for Systemic Lupus Erythematosus: Protocol for a Multicenter Randomized Controlled Trial. JMIR Res Protoc. 2023 Oct 13;12:e48387. doi: 10.2196/48387.

  PMID: 37831494 DERIVED

Related Links

• Framework of the general project lead by Iván Contreras : VaNeSA

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases

Central Study Contacts

Judith Navarro, MD

CONTACT

0034; JNAVARR1@clinic.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Neurologist

Model Details: VaNeSA is a multicentre, national, randomized, double-blind, parallel-group, placebo-controlled, outpatient study.

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: January 30, 2023
• Study Start: September 30, 2022
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)