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Axial SpondyloarthritisESNV-SPANCT04286373

Efficacy of Non-invasive Vagus Nerve Stimulation for Axial Spondyloarthritis Resistant to Biotherapies

A study of Axial Spondyloarthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

The primary objective of the study is to study the change in SpA disease activity, according to ASAS20 definition (Anderson et al., 2001), after 8 weeks of VNS treatment versus placebo non-specific stimulation (control group). Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Axial Spondyloarthritis
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
1 siteFrance
Study dates
Sep 2025to Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient from 18 to 90 years with axial SpA, meeting the ASAS classification criteria, followed for at least one year, with presence of radiological sacro-illitis (ankylosing spondylitis) or not;
  • Patient suffering active SpA, with or without treatment, having a total BASDAI score ≥ 4 (0-10) at baseline and a score of global pain ≥ 4 (0-10);
  • SpA insufficiently relieved despite optimal drug management for at least 6 months including at least 2 different NSAIDs at the maximum tolerated dose for at least 3 months (or less in case of intolerance) and at least two lines of biotherapies or discontinued SpA treatments due to intolerance, contraindication.

Who cannot join

  • Patient under guardianship;
  • Cardiac arrhythmia;
  • Patients with cochlear implant;
  • Patients with known heart disease;
  • Hypotension;
  • Asthmatic patients;
Show all 12Show fewer
  • Refusal to participate in the study or to sign the informed consent;
  • Pregnant or breastfeed woman;
  • No affiliation to a social security scheme;
  • Previous VNS treatment;
  • Incapacity to attend the weekly appointment during the study period;
  • 12- Head trauma with fracture of rock. In case of skin lesions of the left ear, recruitment will be delayed until these lesions are healed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Eric AZABOU, MD, PhD contact

+ 33 1 47 10 79 40

eric.azabou@aphp.fr

France1 site

  • Neurophysiology and Neuromodulation Unit, Department of Physiology, Raymond Poincaré Hospital, APHP

    Garches, Hauts-de-seine, 92380

Other trials in France

About this study

Official title: Randomized Cross Over Study Assessing the Effectiveness of Non-invasive Vagus Nerve Stimulation in Patients With Axial Spondyloarthritis Resistant to Biotherapies

The primary objective of the study is to study the change in SpA disease activity, according to ASAS20 definition (Anderson et al., 2001), after 8 weeks of VNS treatment versus placebo non-specific stimulation (control group).

The secondary objectives of the Clinical Investigation are to show differences in disease evolution between the active and placebo periods of 8 weeks treatment with active VNS versus placebo VNS of the following items:

  1. Change in disease activity according to "ASAS40" criteria
  2. Obtaining a partial remission according to the ASAS definition
  3. Change in BASFI
  4. Change in C-reactive protein (CRP)serum level and erythrocytes sedimentation rate (ESR),
  5. Change in ASDAS_CRP and ASDAS_ESR
  6. Difference in levels of circulating cytokines, IL-6, IL-23, IL-17, IL-33 and of matrix metallopeptidases (MMP3-8-9).
  7. Change in quality of life : assessment according to the following indexes: SF-36, AS Quality of Life (ASQOL)
  8. Change in Health Index of patient with SpA (ASAS HI) and of the Productivity at Work Index (WPI)
  9. Change in fatigue (BASDAI 1st question) and global pain
  10. Change in Anxiety and Depression Assessment (HAD)
  11. Change in BASMI
  12. Change in non-steroidal anti-inflammatory drugs (NSAID) intake score.
Read the detailed description

This multi-center study will be conducted in rheumatology departments of 14 public hospitals in France.

The study is part of the SMART-VNS (TM) project: a Structured Multidisciplinary Program for Advanced Research on the Therapeutic effects of Vagus Nerve Stimulation in inflammatory, infectious, neurological and painful diseases.

After informed consent, patients will be included in the Clinical Investigation by rheumatologists during routine consultations. Included patients will be randomised in two groups differing by the sequence in which the treatments are to be administered: Group A: VNS active for 8 weeks, then VNS placebo for 8 weeks; and Group B: VNS placebo for 8 weeks then VNS active for 8 weeks. In order to maintain the blind, investigators administering the stimulation will be different from those evaluating the patients, and the latter will be blinded to the treatment administered. A transcutaneous vagus nerve stimulator Tens Eco Plus SCHWA MEDICO™ will be used in this Clinical Investigation during the active VNS periods. The active VNS stimulation will be applied in the hollow of the left outer ear on the auricular branch of the vagus nerve (cymba conchae), a session of 1 hour of stimulation per week, at a weak intensity value (between 2 to 5 mA). During the placebo VNS periods, VNS placebo stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at a different site: the left ear lobule according to previously published methods (Frangos et al., 2015, Fang et al., 2017). All randomized patients will be followed up until the end of their stimulation periods. Data collection for the assessment of endpoints will be performed by biochemistry tests and questionnaires in all patients at the first and the last visit of each period.

Being tested
active stimulation then placebo stimulation, placebo stimulation then active stimulation
Keywords
axial spondyloarthritis, vagus nerve stimulation
Medical subject headings
Axial Spondyloarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • active stimulation then placebo stimulationDevice

    The active VNS stimulation will be applied in the hollow of the left outer ear on the auricular branch of the vagus nerve (cymba conchae), a session of 1 hour of stimulation per week, at a weak intensity value (between 2 to 5 mA), depending on the tolerance of each patient.

    A transcutaneous vagus nerve stimulator Tens Eco Plus SCHWA MEDICO™ France with the Garches Azabou-Bao vagal electrode (the G electrode) will be used in this Clinical Investigation.

    VNS placebo stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at a different site: the left ear lobule according to previously published methods (Fang et al. 2017, Frangos et al. 2015).

    The two stimulation periods will be separated by a 4 weeks wash-out period.

  • placebo stimulation then active stimulationDevice

    VNS placebo stimulation will be performed under the same conditions and parameters as active VNS stimulation, but at a different site: the left ear lobule according to previously published methods (Fang et al. 2017, Frangos et al. 2015).

    The active VNS stimulation will be applied in the hollow of the left outer ear on the auricular branch of the vagus nerve (cymba conchae), a session of 1 hour of stimulation per week, at a weak intensity value (between 2 to 5 mA), depending on the tolerance of each patient.

    A transcutaneous vagus nerve stimulator Tens Eco Plus SCHWA MEDICO™ France with the Garches Azabou-Bao vagal electrode (the G electrode) will be used in this Clinical Investigation.

    The two stimulation periods will be separated by a 4 weeks wash-out period.

Study groups in NCT04286373
Study groupRoleWhat they receive
Group A: active stimulation then placebo stimulationExperimentalVNS active stimulation: Use of device (Tens Eco Plus SCHWA MEDICO™) for 8 weeks, then VNS placebo for 8 weeks. The two stimulation periods will be separated by a 4 +/- 1 weeks wash-out period. The VNS placebo stimulation period being the control one.
Receives: Device: active stimulation then placebo stimulation
Group B: placebo stimulation then active stimulationExperimentalVNS placebo for 8 weeks, then VNS active stimulation Use of device (Tens Eco Plus SCHWA MEDICO™) for 8 weeks. The two stimulation periods will be separated by a 4 +/- 1 weeks wash-out period. The VNS placebo stimulation period being the control one.
Receives: Device: placebo stimulation then active stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change according to the ASAS Response Criteria (ASAS 20)

    Assessement of efficacy of VNS treatment: for SpA patients under VNS treatment and under placebo non-specific stimulation, to demonstrate improvement of VNS treatment, according to ASAS20 definition, greater than placebo non-specific stimulation.

    ASAS20 Response is defined as follows: an improvement of 20% compared to baseline and an absolute improvement from baseline of at least 1 unit, in 3 of the 4 ASAS domains: as well as no baseline deterioration of 20% and of at least one unit in the fourth domain.

    Measured: At baseline and week 12

Secondary outcomes (17)

  1. Improvement according to "ASAS40" criteria

    A 40% improvement "ASAS40" after VNS treatment

    Measured: at baseline, 3 months, 4 months ans 7 months

  2. Partial remission

    Partial remission according to the ASAS definition

    Measured: at baseline, 3 months, 4 months ans 7 months

  3. Improvement of BASFI

    Measured: at baseline, 3 months, 4 months ans 7 months

  4. Serum CRP level

    Changes of C-reactive protein (CRP) serum level

    Measured: at baseline, 3 months, 4 months ans 7 months

  5. Serum ESR

    Changes of serum erythrocytes sedimentation rate (ESR)

    Measured: at baseline, 3 months, 4 months ans 7 months

  6. ASDAS_CRP

    Changes of ASDAS_CRP

    Measured: at baseline, 3 months, 4 months ans 7 months

  7. ASDAS_ESR

    Changes of ASDAS_ESR

    Measured: at baseline, 3 months, 4 months ans 7 months

  8. Circulating cytokines level of IL-6, IL-17, IL-23, IL-33, and MMP-3-8-9

    Difference in levels of circulating cytokines: IL-6, IL-23,IL-17, IL-33 and of matrix metallopeptidases (MMP3-8-9)

    Measured: at baseline, 3 months, 4 months ans 7 months

  9. Quality of life: SF-36

    Assessement of quality of life: according to the following indexes: SF-36

    Measured: at baseline, 3 months, 4 months ans 7 months

  10. Quality of life: AS Quality of Life (ASQOL)

    Assessement of quality of life: according to the AS Quality of Life (ASQOL).

    Measured: at baseline, 3 months, 4 months ans 7 months

  11. ASAS-HI

    Change of Health Index of patient with SpA (ASAS HI)

    Measured: at baseline, 3 months, 4 months ans 7 months

  12. WPI Productivity Index

    Change of Health Index of patient with the WPI Productivity Index

    Measured: at baseline, 3 months, 4 months ans 7 months

  13. Fatigue severity evaluation

    A visual analogue scale (VAS) will be used to evaluate fatigue severity

    Measured: at baseline, 3 months, 4 months ans 7 months

  14. Global Pain assessment

    Global Pain assessment will be used.

    Measured: at baseline, 3 months, 4 months ans 7 months

  15. Anxiety and Depression Assessment

    Anxiety and Depression Assessment : HAD

    Measured: at baseline, 3 months, 4 months ans 7 months

  16. BASMI

    Measured: at baseline, 3 months, 4 months ans 7 months

  17. Non-steroidal anti-inflammatory drugs (NSAID) intake score

    Change of non-steroidal anti-inflammatory drugs (NSAID) intake score

    Measured: at baseline, 3 months, 4 months ans 7 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2020
  2. Study startSep 2025 (estimated)
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04286373
Sponsor's protocol ID
APHP180602
Other IDs
2020-A00379-30
Acronym
ESNV-SPA
Status last verified
Apr 2025
First submitted
31 Jan 2020
Last updated
27 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Azabou E, Bao G, Costantino F, Jacota M, Lazizi C, Nkam L, Rottman M, Roux AL, Chevallier S, Grimaldi L, Breban M. Randomized Cross Over Study Assessing the Efficacy of Non-invasive Stimulation of the Vagus Nerve in Patients With Axial Spondyloarthritis Resistant to Biotherapies: The ESNV-SPA Study Protocol. Front Hum Neurosci. 2021 Jun 30;15:679775. doi: 10.3389/fnhum.2021.679775. eCollection 2021.

    PubMed 34276328

Questions about this trial

What is this clinical trial studying?

A study of Axial Spondyloarthritis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Eric AZABOU, MD, PhD (+ 33 1 47 10 79 40, eric.azabou@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change according to the ASAS Response Criteria (ASAS 20) (time frame: At baseline and week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04286373, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025.

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