EVNS-SpA: Efficacy of Non-invasive Vagus Nerve Stimulation for Treatment of Axial Spondyloarthritis Resistant to Biotherapies
Study Details
Study Description
Brief Summary
The primary objective of the study is to demonstrate a greater proportion of patients with significant improvement, according to ASAS20 definition, after 12 weeks of vagus nerve stimulation (VNS) treatment than with placebo non-specific stimulation (control group).
The secondary objectives of the study are to show differences in improvement between the active and placebo periods of treatment with active SNV and SNV placebo of the following items:
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Improvement according to "ASAS40" criteria
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Obtaining a partial remission according to the ASAS definition
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Improvement of BASFI
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Decrease of C-reactive protein (CRP) serum level and erythrocytes sedimentation rate (ESR),
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Improvement of ASDAS_CRP and ASDAS_ESR
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Difference in levels of circulating cytokines: IL-6, IL-23, IL-17, IL-33 and of matrix metallopeptidases (MMP3-8-9)
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Improvement of quality of life: assessment according to the following indexes: SF-36, AS Quality of Life (ASQOL)
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Improvement of Health Index of patient with SpA (ASAS HI) and of the Productivity at Work Index (WPI)
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Improvement of fatigue (BASDAI 1st question) and global pain
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Improvement of Anxiety and Depression Assessment (HAD)
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Improvement of BASMI
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Decrease of non-steroidal anti-inflammatory drugs (NSAID) intake score.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The efficacy of non-invasive VNS therapy in patients with axial SpA has never been studied. This study will assess the benefit-risk balance of the therapy through a randomized double-blind cross over clinical trial.
This multi-center study will be conducted in rheumatology departments of 17 public hospitals in France.
A transcutaneous vagus nerve stimulator Tens Eco 2 SCHWA MEDICO™ France will be used in this study. Before the beginning of the study, a VNS practical training seminar will be organized in order for all future investigators.
All patients eligible for this study must have been previously treated according to national and international guidelines for patients with axial SpA. Adult patients with axial SpA diagnosed and followed for at least one year, insufficiently relieved despite optimal drug management, including at least two lines of biotherapies tested for at least 6 months, will be enrolled in this study.
The duration of participation (treatment + follow-up) for each patient: 7 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active stimulation then placebo stimulation VNS active for 12 weeks, then VNS placebo for 12 weeks. The VNS placebo stimulation period being the control one. |
Device: active stimulation then placebo stimulation
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.
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.
|
| Experimental: Placebo stimulation then active stimulation VNS placebo for 12 weeks, then VNS active for 12 weeks. The VNS placebo stimulation period being the control one. |
Device: placebo stimulation then active stimulation
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.
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.
|
Outcome Measures
Primary Outcome Measures
- Change according to the ASAS Response Criteria (ASAS 20) [At baseline and week 12]
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.
Secondary Outcome Measures
- Improvement according to "ASAS40" criteria [at baseline, 3 months, 4 months ans 7 months]
A 40% improvement "ASAS40" after VNS treatment
- Partial remission [at baseline, 3 months, 4 months ans 7 months]
Partial remission according to the ASAS definition
- Improvement of BASFI [at baseline, 3 months, 4 months ans 7 months]
- Serum CRP level [at baseline, 3 months, 4 months ans 7 months]
Changes of C-reactive protein (CRP) serum level
- Serum ESR [at baseline, 3 months, 4 months ans 7 months]
Changes of serum erythrocytes sedimentation rate (ESR)
- ASDAS_CRP [at baseline, 3 months, 4 months ans 7 months]
Changes of ASDAS_CRP
- ASDAS_ESR [at baseline, 3 months, 4 months ans 7 months]
Changes of ASDAS_ESR
- Circulating cytokines level of IL-6, IL-17, IL-23, IL-33, and MMP-3-8-9 [at baseline, 3 months, 4 months ans 7 months]
Difference in levels of circulating cytokines: IL-6, IL-23,IL-17, IL-33 and of matrix metallopeptidases (MMP3-8-9)
- Quality of life: SF-36 [at baseline, 3 months, 4 months ans 7 months]
Assessement of quality of life: according to the following indexes: SF-36
- Quality of life: AS Quality of Life (ASQOL) [at baseline, 3 months, 4 months ans 7 months]
Assessement of quality of life: according to the AS Quality of Life (ASQOL).
- ASAS-HI [at baseline, 3 months, 4 months ans 7 months]
Change of Health Index of patient with SpA (ASAS HI)
- WPI Productivity Index [at baseline, 3 months, 4 months ans 7 months]
Change of Health Index of patient with the WPI Productivity Index
- Fatigue severity evaluation [at baseline, 3 months, 4 months ans 7 months]
A visual analogue scale (VAS) will be used to evaluate fatigue severity
- Global Pain assessment [at baseline, 3 months, 4 months ans 7 months]
Global Pain assessment will be used.
- Anxiety and Depression Assessment [at baseline, 3 months, 4 months ans 7 months]
Anxiety and Depression Assessment : HAD
- BASMI [at baseline, 3 months, 4 months ans 7 months]
- Non-steroidal anti-inflammatory drugs (NSAID) intake score [at baseline, 3 months, 4 months ans 7 months]
Change of non-steroidal anti-inflammatory drugs (NSAID) intake score
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult patient with axial SpA, meeting the ASAS classification criteria, followed for at least one year, with presence of radiological sacro-iliitis (ankylosing spondylitis) or not;
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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);
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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.
Exclusion Criteria:
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Patient under guardianship;
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Cardiac arrhythmia;
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Refusal to participate in the study or to sign the informed consent;
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Pregnant or breastfeed woman;
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No affiliation to a social security scheme;
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Previous VNS treatment;
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Incapacity to attend the weekly appointment during the study period.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Neurophysiology Laboratory, Department of Physiology and Functional Explorations, Raymond Poincaré Hospital, APHP | Garches | Hauts-de-seine | France | 92380 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
- Principal Investigator: Eric AZABOU, MD, PhD, Clinical Neurophysiology Laboratory, Department of Physiology and Functional Explorations, Raymond Poincaré Hospital, APHP
- Study Director: Maxime Breban, MD, PhD, Department of Rheumatology, Ambroise Paré Hospital, APHP
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PHRC 18 0460