Clinical trial NCT05704153: Modelling and Control of Non-invasive Vagus Nerve Stimulation for Autoimmune Diseases (1A)
Official title: Modelling and Control of Non-invasive Vagus Nerve Stimulation for Autoimmune Diseases (1A)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Systemic Lupus Erythematosus
Autoimmune Disorder
Vagus Nerve Autonomic Disorder
Keywords: Parasympathetic Nervous System
Vagus Nerve Stimulation
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: Universitat de Girona
name: Hospital Mutua de Terrassa
name: Imperial College London
name: Johns Hopkins University
First posted: 2023-01-30
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: VaNeSA is a multicentre, national, randomized, double-blind, parallel-group, placebo-controlled, outpatient study.
Primary purpose: SCREENING

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Haemoglobin below 9.0 gm/dL (by the most recent CBC) as anaemia is related to no- neurogenic orthostatic hypotension and increases cardiovascular symptoms in COMPASS 31 scale
* Comorbid disease that may require administration of corticosteroid use.
* Inability to comply with study and follow-up procedures.
* Known cardiac arrhythmia, severe cardiac disease or neurodegenerative disease.
* Known or confirmed at baseline screening peripheral or autonomic nervous system involvement, including LES-related, toxic polyneuropathies, metabolic neuropathies (including diabetes), etc.
* Previous experience with vagus nerve stimulation devices

Primary outcomes:
measure: Number of patients with Systemic Lupus Erythematosus with clinical and analytic change after non-invasive vagus nerve stimulation (nVNS) at different waveform parameters
timeFrame: Visit 1(baseline, exploratory study, up to 30days prior to first nVNS)
Secondary outcomes:
measure: Blood count
timeFrame: 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
measure: Erythrocyte sedimentation rate
timeFrame: 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
measure: C-reactive protein
timeFrame: 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
measure: Anti-dsDNA
timeFrame: 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
measure: C3, C4
timeFrame: 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
measure: Tumoral necrosis factor (TNF), Interleukin (IL) -6, IL-10 and Il1B
timeFrame: 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
measure: High mobility group box 1 protein (HMGB1)
timeFrame: 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
measure: Alpha interferon (IFNα)
timeFrame: 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
measure: EuroQol-5D (EQ-5D-5L),
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels and 1 month after nVNS.
measure: Lupus Patient-Reported Outcome (LupusPRO)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Lupus Quality of Life (LupusQoL)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Fatigue Severity Scale (FSS)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Composite Autonomic Symptom Score (Compass-31)
timeFrame: 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
measure: 28-joint count
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Physician's Global Assessment (PGA)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Patients' Global Assessment (PtGA)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Numeric scale ranges (NRS)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: Visual Analog Scale (VAS)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: High-frequency power, low-frequency power
timeFrame: 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
measure: LF to HF power ratio
timeFrame: 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
measure: Cardiovagal evaluation. (Composite autonomic scoring scale)
timeFrame: 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
measure: Vasalva ratio
timeFrame: 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
measure: Sympathetic evaluation (Composite autonomic scoring scale)
timeFrame: 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
measure: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
measure: BILAG-2004
timeFrame: Baseline, days 1-2-3-4-5 of nVNS, after five days of nVNS, after 2 weeks of nVNS, after3 weeks of nVSN. Additionally, 2 and 3months after stimulation if the biomarkers and scales of activity do not return to baseline levels
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic
Study officials:
References: