search
Back to results

Efficacy of Non-invasive Vagus Nerve Stimulation for Axial Spondyloarthritis Resistant to Biotherapies (ESNV-SPA II)

Primary Purpose

Axial Spondyloarthritis

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
active stimulation then placebo stimulation
placebo stimulation then active stimulation
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Axial Spondyloarthritis focused on measuring axial spondyloarthritis, vagus nerve stimulation

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group A: active stimulation then placebo stimulation

Group B: placebo stimulation then active stimulation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Improvement according to "ASAS40" criteria
A 40% improvement "ASAS40" after VNS treatment
Partial remission
Partial remission according to the ASAS definition
Improvement of BASFI
Serum CRP level
Changes of C-reactive protein (CRP) serum level
Serum ESR
Changes of serum erythrocytes sedimentation rate (ESR)
ASDAS_CRP
Changes of ASDAS_CRP
ASDAS_ESR
Changes of ASDAS_ESR
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)
Quality of life: SF-36
Assessement of quality of life: according to the following indexes: SF-36
Quality of life: AS Quality of Life (ASQOL)
Assessement of quality of life: according to the AS Quality of Life (ASQOL).
ASAS-HI
Change of Health Index of patient with SpA (ASAS HI)
WPI Productivity Index
Change of Health Index of patient with the WPI Productivity Index
Fatigue severity evaluation
A visual analogue scale (VAS) will be used to evaluate fatigue severity
Global Pain assessment
Global Pain assessment will be used.
Anxiety and Depression Assessment
Anxiety and Depression Assessment : HAD
BASMI
Non-steroidal anti-inflammatory drugs (NSAID) intake score
Change of non-steroidal anti-inflammatory drugs (NSAID) intake score

Full Information

First Posted
January 31, 2020
Last Updated
August 25, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
search

1. Study Identification

Unique Protocol Identification Number
NCT04286373
Brief Title
Efficacy of Non-invasive Vagus Nerve Stimulation for Axial Spondyloarthritis Resistant to Biotherapies
Acronym
ESNV-SPA II
Official Title
Randomized Cross Over Study Assessing the Effectiveness of Non-invasive Vagus Nerve Stimulation in Patients With Axial Spondyloarthritis Resistant to Biotherapies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Axial Spondyloarthritis
Keywords
axial spondyloarthritis, vagus nerve stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A: active stimulation then placebo stimulation
Arm Type
Experimental
Arm Description
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.
Arm Title
Group B: placebo stimulation then active stimulation
Arm Type
Experimental
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
active stimulation then placebo stimulation
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
placebo stimulation then active stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change according to the ASAS Response Criteria (ASAS 20)
Description
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.
Time Frame
At baseline and week 12
Secondary Outcome Measure Information:
Title
Improvement according to "ASAS40" criteria
Description
A 40% improvement "ASAS40" after VNS treatment
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Partial remission
Description
Partial remission according to the ASAS definition
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Improvement of BASFI
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Serum CRP level
Description
Changes of C-reactive protein (CRP) serum level
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Serum ESR
Description
Changes of serum erythrocytes sedimentation rate (ESR)
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
ASDAS_CRP
Description
Changes of ASDAS_CRP
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
ASDAS_ESR
Description
Changes of ASDAS_ESR
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Circulating cytokines level of IL-6, IL-17, IL-23, IL-33, and MMP-3-8-9
Description
Difference in levels of circulating cytokines: IL-6, IL-23,IL-17, IL-33 and of matrix metallopeptidases (MMP3-8-9)
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Quality of life: SF-36
Description
Assessement of quality of life: according to the following indexes: SF-36
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Quality of life: AS Quality of Life (ASQOL)
Description
Assessement of quality of life: according to the AS Quality of Life (ASQOL).
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
ASAS-HI
Description
Change of Health Index of patient with SpA (ASAS HI)
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
WPI Productivity Index
Description
Change of Health Index of patient with the WPI Productivity Index
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Fatigue severity evaluation
Description
A visual analogue scale (VAS) will be used to evaluate fatigue severity
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Global Pain assessment
Description
Global Pain assessment will be used.
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Anxiety and Depression Assessment
Description
Anxiety and Depression Assessment : HAD
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
BASMI
Time Frame
at baseline, 3 months, 4 months ans 7 months
Title
Non-steroidal anti-inflammatory drugs (NSAID) intake score
Description
Change of non-steroidal anti-inflammatory drugs (NSAID) intake score
Time Frame
at baseline, 3 months, 4 months ans 7 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eric AZABOU, MD, PhD
Phone
+ 33 1 47 10 79 40
Email
eric.azabou@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric AZABOU, MD, PhD
Organizational Affiliation
Neurophysiology and Neuromodulation Unit, Department of Physiology, Raymond Poincaré Hospital, APHP
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Maxime Breban, MD, PhD
Organizational Affiliation
Department of Rheumatology, Ambroise Paré Hospital, APHP
Official's Role
Study Director
Facility Information:
Facility Name
Neurophysiology and Neuromodulation Unit, Department of Physiology, Raymond Poincaré Hospital, APHP
City
Garches
State/Province
Hauts-de-seine
ZIP/Postal Code
92380
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34276328
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs