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

NCT04286373 | Not Yet Recruiting DMC

• 2 other identifiers: APHP1806022020-A00379-30
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Conditions

Axial Spondyloarthritis

Keywords

axial spondyloarthritis; vagus nerve stimulation

Outcome Measures

Primary Outcomes (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.

  At baseline and week 12

Secondary Outcomes (17)

• Improvement according to "ASAS40" criteria

  at baseline, 3 months, 4 months ans 7 months

• Partial remission

  at baseline, 3 months, 4 months ans 7 months

• Improvement of BASFI

  at baseline, 3 months, 4 months ans 7 months

• Serum CRP level

  at baseline, 3 months, 4 months ans 7 months

• Serum ESR

  at baseline, 3 months, 4 months ans 7 months

Study Arms (2)

Group A: active stimulation then placebo stimulation

EXPERIMENTAL

VNS 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.

Device: active stimulation then placebo stimulation

Group B: placebo stimulation then active stimulation

EXPERIMENTAL

VNS 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.

Device: placebo stimulation then active stimulation

Interventions

active stimulation then placebo stimulation DEVICE

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.

Group A: active stimulation then placebo stimulation

placebo stimulation then active stimulation DEVICE

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.

Group B: placebo stimulation then active stimulation

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patient under guardianship;
• Cardiac arrhythmia;
• Patients with cochlear implant;
• Patients with known heart disease;
• Hypotension;
• Asthmatic patients;
• 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;
• Head trauma with fracture of rock. In case of skin lesions of the left ear, recruitment will be delayed until these lesions are healed.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

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

Garches, Hauts-de-seine, 92380, France

Location

Related Publications (1)

• 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.

  PMID: 34276328 DERIVED

MeSH Terms

Conditions

Axial Spondyloarthritis

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Eric AZABOU, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Maxime Breban, MD, PhD

  Department of Rheumatology, Ambroise Paré Hospital, APHP

  STUDY DIRECTOR

Central Study Contacts

Eric AZABOU, MD, PhD

CONTACT

+ 33 1 47 10 79 40; eric.azabou@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 27, 2020
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)