- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04520516
Auricular Vagus Nerve Stimulation in Painful and Inflammatory Erosive Hand Osteoarthritis (ESTIVAL)
Trial of Auricular Vagus Nerve Stimulation in Painful and Inflammatory Erosive Hand Osteoarthritis
Erosive hand osteoarthritis (EHOA) is a difficult-to-treat subtype of HOA characterized by local and systemic low-grade inflammation as well as by high level of pain and of disability.
Auricular transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic strategy that may reduce inflammation and pain level.
ESTIVAL is a 12 weeks randomized sham-controlled trial investigating the symptomatic efficacy and safety of tVNS in patients with symptomatic and inflammatory EHOA.
tVNS will be performed using a transcutaneous electrical nerve stimulation (TENS) device connected to an auricular electrode stimulating the cutaneous area of the left ear innervated by the auricular ascendant branch of the vagus nerve.
The active and sham device's will display similar appearance but the sham one will not give electric signal.
Study Overview
Status
Intervention / Treatment
Detailed Description
Symptomatic hand osteoarthritis (HOA) affects 8-16% of the general population above 50 years and involves interphalangeal (IP) joints. HOA symptoms include pain, stiffness and are responsible for disability and substantial burden. Erosive HOA (EHOA) (10% prevalence among symptomatic HOA from the general population and 40-50% prevalence in tertiary centers) is the most severe HOA phenotype characterized by inflammatory flares, more IP joint destruction, pain, soft swelling joints (ie, synovitis), and more disability (similar to rheumatoid arthritis (RA)) than its non-erosive counterpart.
Current symptomatic pharmacological treatments of HOA or EHOA have a poor efficacy on pain (ie, paracetamol) or safety issues (ie, non-steroidal anti-inflammatory drugs (NSAIDs)) in this aging population with frequent comorbidities. Systemic and joint inflammation contribute to EHOA but 4 studies using TNF inhibitors, 2 using hydroxychloroquine, 1 using methotrexate and 1 using a new anti-IL1α/β failed to show any efficacy on pain in HOA or in EHOA. Therefore, innovative therapeutic approaches are awaited.
Stimulation of the vagus nerve (VNS), belonging to parasympathetic system, dampens pro-inflammatory cytokines production by splenic macrophages, through to the binding of acetylcholine neurotransmitter to α7nicotinic receptor on macrophages: this is the cholinergic anti-inflammatory pathway (CAP). VN stimulation (VNS) by cervical implantable device activating CAP has given promising results in refractory RA patients. Beyond its anti-inflammatory effects, VNS is analgesic in chronic pain disorders (headache, fibromyalgia). However, the use of such implantable device is limited by the need of cervical surgery and subsequent potential side effects.
Besides implantable devices, VNS may be also performed using transcutaneous VNS (tVNS) of the ascendant auricular branch of the VN that selectively innervates the cutaneous zone of cymba conchae at the left ear. Auricular tVNS avoids invasive neurosurgery and its potential side effects and is less expensive than implantable VNS, making it an attractive candidate for neurostimulation. Auricular tVNS has given positive results in chronic migraine and is currently tested in RA, Crohn's disease, widespread pain, irritable bowel syndrome and musculoskeletal pain related to systemic lupus.
We hypothesize that auricular tVNS using a transcutaneous electrical nerve stimulation (TENS) device could be a novel, simple and well-tolerated analgesic and anti-inflammatory treatment of symptomatic (i.e., painful) and inflammatory EHOA.
ESTIVAL is a 12 weeks randomized sham-controlled trial investigating the symptomatic efficacy and the safety of tVNS in patients with symptomatic and inflammatory EHOA.
tVNS will be performed using an active or sham transcutaneous electrical nerve stimulation (TENS) device connected to an auricular electrode stimulating the cutaneous area of the left ear innervated by the auricular ascendant branch of the vagus nerve.
Exploratory and ancillary studies will include i) changes of serum biomarkers of inflammation and of cartilage degradation that will be assess at inclusion and at week 12 ii) hand MRI at W0 and W12 of the most symptomatic joint at inclusion for HOAMRIS socring at W0 and W12 for the center of Saint Antoine.
A phone call at D7± 3 days by the clinical research technician or the clinical nurse or the doctor who has performed the education during the D0 visit to check the proper use of the device.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Paris, France, 75012
- Service de Rhumatologie - Hôpital Saint Antoine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥ 18 years
- Symptomatic HOA according to the American College of Rheumatology criteria
- Erosive HOA according to hand radiographs performed in routine practice showing ≥1 erosive digital joint based on Verbruggen-Veys scoring definition
- Hand pain level ≥ 40/100 mm on VAS at inclusion at least half of days of the 30 last days
- At least ≥1 symptomatic IP joint with clinical soft swelling or erythema at inclusion
- reported inadequate response or adverse effects or contraindication with existing medication (including acetaminophen, oral NSAIDs)
- Informed written consent
- Patient affiliated to a social security scheme NB: Clinical inflammation, ultrasound abnormalities and radiographic erosions have not have to be present in the same joint.
Exclusion Criteria:
- Isolated thumb-base OA (i.e., rhizarthrosis)
- Predominance of the pain in the thumb base rather than digital pain
- Other inflammatory joint disease (e.g. gout, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, Lyme disease)
- Psoriasis
- Current skin disease of the left ear (e.g., eczema, urticarial lesion, skin infection, external otitis)
- Ear canal not adapted to apply the auricular electrode
- Known history of cardiac rhythm disturbances, atrio-ventricular block > first degree, or total bundle branch block
- Symptomatic orthostatic hypotension or repeated vasovagal syncope history
- History of vagotomy
- Severe Asthma
- Treated sleep apnea
- Existence of a pain syndrome of the upper limbs, which would interfere with the monitoring of pain
- Fibromyalgia
- Use of other electrically active medical devices (e.g. pacemaker, TENS for chronic pain)
- Use of oral, intramuscular or intra-articular or intravenous steroids, other anti-synovial agents (e.g. slow-acting anti-rheumatic drugs such as methotrexate, sulfasalazine), intra-articular hyaluronic acid to the hand joints within the last 3 months
- Any new hand OA treatment in the previous 2 months, including physiotherapy and provision of new hand splint.
- Planned hand surgery in the next 3 months.
- Use of any investigational (unlicensed) drug within 3 months prior to screening.
- Evidence of serious uncontrolled concomitant medical condition, including cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, gastro-intestinal disease or epilepsy, which in the opinion of the investigator makes them unsuitable for the study
- Pregnant or breastfeeding woman
- Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom
- Use of VNS before the study
- Use of NSAIDs or paracetamol less than 48h before the D0 visit
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: tVNS active device
VAGUSTIM device from Schwa-Medico Length of use : 12 weeks
|
20min/day of stimulation at 25 Hz Frequency, 50 microsec pulse width with intensity escalation up to 15 mA or below in case of auricular discomfort
|
Sham Comparator: Sham tVNS device
Sham VAGUSTIM device from Schwa-Medico Length of use : 12 weeks
|
The sham device : no electrical signal for VNS will be delivered.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from Day 0 to Week 12 of self-reported hand pain
Time Frame: 12 weeks
|
Change from Day 0 to Week 12 of self-reported hand pain in the previous 48 hours measured on a 100 mm visual analogue scale (VAS) : "How much pain in your hands did you experience during the past 48 h?"
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
AUStralian CANadian Osteoarthritis Hand Index (AUSCAN) 3.1
Time Frame: 12 weeks
|
AUStralian CANadian Osteoarthritis Hand Index (AUSCAN) 3.1 pain, function and stiffness subscores (for each subscore: 0-100 mm scale)
|
12 weeks
|
Function
Time Frame: 12 weeks
|
Modified Functional Index for Hand OsteoArthritis (FIHOA) scale minimum 0 , and maximum 30.
|
12 weeks
|
global response to treatment (on pain, function and global assessment)
Time Frame: 12 weeks
|
proportion of OMERACT-OARSI responders
|
12 weeks
|
Percentage of patients below the Patient Acceptable Symptom State (PASS) of pain (VAS<40/100)
Time Frame: 12 weeks
|
12 weeks
|
|
side effects
Time Frame: 4, 8 and 12 weeks
|
report of side effects during the study period
|
4, 8 and 12 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jérémie SELLAM, Professor, Assistance Publique - Hôpitaux de Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- APHP 200014
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Osteoarthritis
-
Sanford HealthActive, not recruitingKnee Osteoarthritis | Hip Osteoarthritis | Shoulder Osteoarthritis | Ankle Osteoarthritis | Wrist OsteoarthritisUnited States
-
University of EdinburghHospital for Special Surgery, New YorkRecruitingKnee Osteoarthritis | Hip Osteoarthritis | Shoulder OsteoarthritisUnited Kingdom
-
Medical University of WarsawUnknownOsteoarthritis | Knee Osteoarthritis | Hip Osteoarthritis | Glenohumeral OsteoarthritisPoland
-
Medical University of WarsawUnknownOsteoarthritis | Knee Osteoarthritis | Hip Osteoarthritis | Glenohumeral OsteoarthritisPoland
-
University of California, San FranciscoStanford University; Robert Wood Johnson FoundationCompletedKnee Osteoarthritis | Hip OsteoarthritisUnited States
-
University of VermontCompletedOsteoarthritis of Knee | Osteoarthritis Of HipUnited States
-
Hospital for Special Surgery, New YorkRoyal Infirmary of EdinburghRecruitingKnee Osteoarthritis | Hip Osteoarthritis | Shoulder OsteoarthritisUnited States, United Kingdom
-
Ottawa Hospital Research InstituteNot yet recruitingKnee Osteoarthritis | Hip Osteoarthritis
-
University Hospital, LilleCompleted
-
Massachusetts General HospitalNewton-Wellesley Hospital; The New England Baptist HospitalCompletedKnee Osteoarthritis | Hip OsteoarthritisUnited States
Clinical Trials on Active VAGUSTIM device
-
Istanbul Gelisim UniversityNot yet recruitingVagus Nerve Stimulation | Electroencephalography | Electromyography
-
Cedars-Sinai Medical CenterNational Institutes of Health (NIH); Indiana UniversityRecruitingAtrial FibrillationUnited States
-
ReShape LifesciencesUnknownObesityUnited States, Australia
-
Case Western Reserve UniversityHighland Instruments, Inc.RecruitingDiabetic Neuropathies | Chronic PainUnited States
-
Neurovalens Ltd.NRI Institute of Medical SciencesRecruiting
-
Temple UniversityNational Institute of Allergy and Infectious Diseases (NIAID)RecruitingDiarrhea | Respiratory Viral Infection | Gastrointestinal Infection | Waterborne DiseasesUnited States
-
CoolTech LLCTerminatedMigraine | Migraine Without Aura | Migraine With Aura | Episodic MigraineUnited States
-
TheranicaCompleted
-
CentraCareElectroCore INCCompletedTraumatic Brain Injury | Acute Brain InjuriesUnited States
-
Virility Medical Ltd.Sintesi Research SrlCompleted