Ignite Creation Date:
2025-12-26 @ 11:48 AM
Ignite Modification Date:
2025-12-26 @ 11:48 AM
Study NCT ID:
NCT04520516
Status:
COMPLETED
Last Update Posted:
2025-09-16
First Post:
2020-08-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Auricular Vagus Nerve Stimulation in Painful and Inflammatory Erosive Hand Osteoarthritis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010003', 'term': 'Osteoarthritis'}, {'id': 'D059352', 'term': 'Musculoskeletal Pain'}], 'ancestors': [{'id': 'D001168', 'term': 'Arthritis'}, {'id': 'D007592', 'term': 'Joint Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D012216', 'term': 'Rheumatic Diseases'}, {'id': 'D009135', 'term': 'Muscular Diseases'}, {'id': 'D010146', 'term': 'Pain'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'SUPPORTIVE_CARE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 148}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-04-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2022-06-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-09-10', 'studyFirstSubmitDate': '2020-08-17', 'studyFirstSubmitQcDate': '2020-08-17', 'lastUpdatePostDateStruct': {'date': '2025-09-16', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2020-08-20', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-06-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'W0-W12 change in the WOMAC for other osteoarthritis sites (hips, knees) if present at inclusion.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Effectiveness of the blinding procedure and the ease of use of the device', 'timeFrame': 'Week 12', 'description': '* Patient satisfaction with the treatment, assessed on a 5-point scale (from very satisfied to not at all satisfied).\n* Ease of use assessed on a 4-point scale (from very easy to very difficult).\n* Indication by patients whether they believe they received the active or sham device. d. Indication by the investigator whether they believe the patient received the active or sham device.'}, {'measure': 'Change in HOAMRIS subscores of synovitis and subchondral bone marrow edema using MRI examination', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Clinical efficacy (primary endpoint and the OMERACT-OARSI response) according clinical, biological or radiographic characteristics at inclusion', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Correlation between baseline biological biomarkers and clinical response in the active group', 'timeFrame': 'Week 12'}], 'primaryOutcomes': [{'measure': 'Change from Day 0 to Week 12 of self-reported hand pain', 'timeFrame': '12 weeks', 'description': '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?"'}], 'secondaryOutcomes': [{'measure': 'AUStralian CANadian Osteoarthritis Hand Index (AUSCAN)(pain, function, stiffness).', 'timeFrame': 'Between week 0 and week 12', 'description': 'AUStralian CANadian Osteoarthritis Hand Index (AUSCAN) 3.1 pain, function and stiffness subscores (for each subscore: 0-100 mm scale)'}, {'measure': 'Modified Functional Index for Hand OsteoArthritis (FIHOA)', 'timeFrame': 'Between week 0 and week 12 vvv', 'description': 'scale minimum 0 , and maximum 30.'}, {'measure': 'Cochin Hand Function Scale.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Percentage of patients below the Patient Acceptable Symptom State (PASS) of pain (VAS<40/100)', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'EuroQoL EQ-5D.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Hospital Anxiety and Depression Scale (HAD).', 'timeFrame': 'Between week 0 and week 12 vvvvvvv'}, {'measure': 'Fatigue intensity on a 0-100 mm VAS', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Number of painful hand joints (0-30) under pressure.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Number of swollen hand joints (0-30).', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Patient Global Assessment (PGA) of health status on a 0-100 mm VAS.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'DN-4 Questionnaire evaluating neuropathic pain.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Change over time of VAS pain.', 'timeFrame': 'Week 0, Week 4, Week 8, and Week 12'}, {'measure': 'Change over time of FIHOA.', 'timeFrame': 'Week 0, Week 4, Week 8, and Week 12'}, {'measure': 'Change over time of AUSCAN (pain, stiffness, and function).', 'timeFrame': 'Week 0, Week 4, Week 8, and Week 12'}, {'measure': 'Percentage of patients with symptom levels below which they consider their condition acceptable (PASS), defined by a VAS <40/100', 'timeFrame': 'Week 12'}, {'measure': 'Proportion of OMERACT-OARSI responders.', 'timeFrame': 'Week 12'}, {'measure': 'Percentage of responders according to the Patient Global Impression of Change (PGIC) score', 'timeFrame': 'Week 12'}, {'measure': 'Total paracetamol consumption (g) divided by treatment duration using a patient-filled diary.', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Change in percentage in serum inflammatory or pain-related markers', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Change in serum cartilage degradation markers (Coll2-1 (a marker of type II collagen denaturation), Coll2-1-NO2).', 'timeFrame': 'Between week 0 and week 12'}, {'measure': 'Proportion of side effects', 'timeFrame': '4 weeks, 8 weeks and 12 weeks', 'description': 'report of side effects during the study period'}, {'measure': "Average daily use duration and cumulative use duration of the Vagustim device since the last visit, collected from the device's tracking system before each visit.", 'timeFrame': 'Between week 0 and week 12'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Musculoskeletal pain', 'Osteoarthritis', 'Neuromodulation'], 'conditions': ['Osteoarthritis', 'Musculoskeletal Pain', 'Erosive Osteoarthritis']}, 'referencesModule': {'references': [{'pmid': '41380709', 'type': 'DERIVED', 'citation': 'Courties A, Tuffet S, Cormier G, Roux CH, Ornetti P, Pers YM, Gottenberg JE, Lespessailles E, Chapurlat R, Arniaud D, Rannou F, Wendling D, Eymard F, Mathieu S, Richette P, Saraux A, Marotte H, Poursac N, Rat AC, Bastard JP, Fellahi S, Henrotin Y, Minssen L, Deprouw C, Nguyen C, Touati A, Berard L, Rousseau A, Simon T, Maheu E, Berenbaum F, Sellam J. Transcutaneous auricular vagus nerve stimulation versus sham stimulation in patients with erosive hand osteoarthritis (ESTIVAL): a randomised, multicentre, double-blind, sham-controlled trial. Lancet Rheumatol. 2025 Dec 8:S2665-9913(25)00226-7. doi: 10.1016/S2665-9913(25)00226-7. Online ahead of print.'}, {'pmid': '35318234', 'type': 'DERIVED', 'citation': 'Courties A, Deprouw C, Rousseau A, Berard L, Touati A, Kalsch J, Villevieille M, Maheu E, Miquel A, Simon T, Berenbaum F, Sellam J; ESTIVAL study group. Transcutaneous vagus nerve stimulation in erosive hand osteoarthritis: protocol for the randomised, double-blind, sham-controlled ESTIVAL trial. BMJ Open. 2022 Mar 22;12(3):e056169. doi: 10.1136/bmjopen-2021-056169.'}]}, 'descriptionModule': {'briefSummary': "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.\n\nAuricular transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic strategy that may reduce inflammation and pain level.\n\nESTIVAL is a 12 weeks randomized sham-controlled trial investigating the symptomatic efficacy and safety of tVNS in patients with symptomatic and inflammatory EHOA.\n\ntVNS 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.\n\nThe active and sham device's will display similar appearance but the sham one will not give electric signal.", 'detailedDescription': "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.\n\nCurrent 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.\n\nStimulation 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.\n\nBesides 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.\n\nWe 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.\n\nESTIVAL is a 12 weeks randomized sham-controlled trial investigating the symptomatic efficacy and the safety of tVNS in patients with symptomatic and inflammatory EHOA.\n\ntVNS 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.\n\nExploratory 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.\n\nA 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years\n* Symptomatic HOA according to the American College of Rheumatology criteria\n* Erosive HOA according to hand radiographs performed in routine practice showing ≥1 erosive digital joint based on Verbruggen-Veys scoring definition\n* Hand pain level ≥ 40/100 mm on VAS at inclusion at least half of days of the 30 last days\n* At least ≥1 symptomatic IP joint with clinical soft swelling or erythema at inclusion\n* reported inadequate response or adverse effects or contraindication with existing medication (including acetaminophen, oral NSAIDs)\n* Informed written consent\n* 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.\n\nExclusion Criteria:\n\n* Isolated thumb-base OA (i.e., rhizarthrosis)\n* Predominance of the pain in the thumb base rather than digital pain\n* Other inflammatory joint disease (e.g. gout, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, Lyme disease)\n* Psoriasis\n* Current skin disease of the left ear (e.g., eczema, urticarial lesion, skin infection, external otitis)\n* Ear canal not adapted to apply the auricular electrode\n* Known history of cardiac rhythm disturbances, atrio-ventricular block \\> first degree, or total bundle branch block\n* Symptomatic orthostatic hypotension or repeated vasovagal syncope history\n* History of vagotomy\n* Severe Asthma\n* Treated sleep apnea\n* Existence of a pain syndrome of the upper limbs, which would interfere with the monitoring of pain\n* Fibromyalgia\n* Use of other electrically active medical devices (e.g. pacemaker, TENS for chronic pain)\n* 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\n* Any new hand OA treatment in the previous 2 months, including physiotherapy and provision of new hand splint.\n* Planned hand surgery in the next 3 months.\n* Use of any investigational (unlicensed) drug within 3 months prior to screening.\n* 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\n* Pregnant or breastfeeding woman\n* Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom\n* Use of VNS before the study\n* Use of NSAIDs or paracetamol less than 48h before the D0 visit'}, 'identificationModule': {'nctId': 'NCT04520516', 'acronym': 'ESTIVAL', 'briefTitle': 'Auricular Vagus Nerve Stimulation in Painful and Inflammatory Erosive Hand Osteoarthritis', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Trial of Auricular Vagus Nerve Stimulation in Painful and Inflammatory Erosive Hand Osteoarthritis', 'orgStudyIdInfo': {'id': 'APHP200014'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'tVNS active device', 'description': 'VAGUSTIM device from Schwa-Medico Length of use : 12 weeks', 'interventionNames': ['Device: Active VAGUSTIM device']}, {'type': 'SHAM_COMPARATOR', 'label': 'Sham tVNS device', 'description': 'Sham VAGUSTIM device from Schwa-Medico Length of use : 12 weeks', 'interventionNames': ['Device: Sham VAGUSTIM device']}], 'interventions': [{'name': 'Active VAGUSTIM device', 'type': 'DEVICE', 'description': 'Settings: 25 Hz stimulation, 100 microsec pulse width, intensity escalation up to 8 mA or below if tingling sensation, 20 min/day of stimulation in one daily session', 'armGroupLabels': ['tVNS active device']}, {'name': 'Sham VAGUSTIM device', 'type': 'DEVICE', 'description': 'The sham device : no electrical signal for VNS will be delivered.', 'armGroupLabels': ['Sham tVNS device']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75012', 'city': 'Paris', 'country': 'France', 'facility': 'Service de Rhumatologie - Hôpital Saint Antoine', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'overallOfficials': [{'name': 'Jérémie SELLAM, Professor', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Assistance Publique - Hôpitaux de Paris'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'Schwa medico (device lending)', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}