Treatment Resistant Depression and Vagus Nerve Stimulation
NCT ID: NCT05952674
Last Updated: 2025-05-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
166 participants
INTERVENTIONAL
2024-09-19
2030-08-19
Brief Summary
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Depression has a major impact on quality of life, socio-professional functioning and healthcare consumption.
Sometimes, TRD is part of a bipolar illness. In this case, the challenge is even bigger because antidepressants are no well tolerated, further reducing the therapeutic options in case of resistance, the severity and duration of the depressive episodes are the main factors explaining the deterioration of the quality of life and the increasing cost of cares for these patients.
The standard treatment for TRD is electroconvulsive therapy (ECT), which results in a response in 60 to 70% of cases after a few weeks of treatment. However, the improvement is often transient and 40% of patients relapse within 6 months of the initial ECT session. Moreover, ECT is often not well tolerated. This therapeutic impasse therefore makes TRD a priority public health target to which it is urgent to provide a realistic medico-economical response.
The literature suggests that Vagus Nerve Stimulation (VNS) has unique kinetics of efficacy in depression, particularly in preventing long-term recurrences, and therefore responding to the lack of effective maintenance treatment in TRD. In fact, the benefits of VNS gradually accumulate over 12-24 months, which makes it complementary to more incisive treatments like ECT. Finally, its efficacy-tolerance profile appears to be similar in uni and bipolar TRD, giving VNS a potentially unique place in the therapeutic arsenal in psychiatry.
The DepVNS hypothesis is that VNS is a medico-economically efficient therapeutic option to overcome the therapeutic impasse in which patients suffering from uni and bipolar DR currently find themselves due to the frequency of relapses under treatment.
The primary objective is to estimate, from a collective point of view, the incremental cost-utility ratio of VNS to treat patients suffering from RD.
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Detailed Description
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Depression has a major impact on quality of life, socio-professional functioning and healthcare consumption. According to the World Health Organization (WHO), depression will be the second cause of healthcare costs in the world by 2020. RD alone accounts for 30 to 40% of the annual cost of depression.
Sometimes, TRD is part of a bipolar illness, a psychiatric condition characterized by the alternation of depressive and maniac episodes that affects 4% of the population. In this case, the challenge is even bigger because (1) antidepressants are no well tolerated, further reducing the therapeutic options in case of resistance, (2) the severity and duration of the depressive episodes are the main factors explaining the deterioration of the quality of life and the increasing cost of cares for these patients. Bipolar RD currently accounts for 20% of all psychiatric spending.
The standard treatment for TRD is electroconvulsive therapy (ECT), which results in a response in 60 to 70% of cases after a few weeks of treatment. However, the improvement is often transient and 40% of patients relapse within 6 months of the initial ECT session. Moreover, ECT is often not well tolerated because of the frequency and the intensity of the memory disorders associated, the repetition of anesthesia and hospitalizations and its social stigma. Refusals and requests to stop ECT are therefore common even when it is effective, as these constraints are sometimes experienced as being unbearable in the long-term. This therapeutic impasse therefore makes TRD a priority public health target to which it is urgent to provide a realistic medico-economical response.
The literature suggests that Vagus Nerve Stimulation (VNS) has unique kinetics of efficacy in depression, particularly in preventing the long-term recurrences, and therefore responding to the lack of effective maintenance treatment in TRD. In fact, the benefits of VNS gradually accumulate over 12-24 months, which makes it complementary to more incisive treatments like ECT. Finally, its efficacy-tolerance profile appears to be similar in uni and bipolar TRD, giving VNS a potentially unique place in the therapeutic arsenal in psychiatry. VNS has been approved for over 15 years as a treatment for RD in the Unites States and Great-Britain.
The hypothesis is that VNS is a medico-economically efficient therapeutic option to overcome the therapeutic impasse in which patients suffering from uni and bipolar DR currently find themselves due to the frequency of relapses under treatment.
The primary objective is to estimate, from a collective point of view, the incremental cost-utility ratio of VNS to treat patients suffering from RD.
The secondary objectives are evaluating the efficacy and the security of the VNS, as well as positioning the VNS in comparison with ECT that is currently the standard treatment for TRD.
This is a national multicenter comparative, open, randomized, controlled, two-parallel group clinical trial evaluating the medico-economic impact of VNS in resistant depression population. Patients (166) suffering from resistant depression will be enrolled over a 24-month period and will be randomized in a (1:1) ratio to receive either Vagus Nerve Stimulation (VNS) along with the Best Medical Treatment (VNS+BMT arm) or the Optimal Medical Treatment only (BMT arm).
Patients meeting all eligibility criteria will be enrolled in the study.
All subjects will be followed by the investigators or designee of the investigator during the whole study period by visits on site.
Number of visits/participant: Both arms will attend: selection visit (VS), inclusion visit (VI) and randomization visit (R), M0, M2, M4, M6, M8, M10, M12, M14, M16, M18, M20, M22 and M24. After the inclusion visit, the experimental arm (VNS + BMT) will further attend a neurosurgical and anesthetic consultation before being hospitalized for the VNS system placement. The patient will finally be hospitalized in psychiatry for about 5 days for switching the device on. If the target intensity has not been reached during this hospitalization, an adjustment visit is planned every month for 6 months in order to progressively increase the stimulation intensity until the target or a therapeutic response. If the target or the therapeutic response is obtained, the settings adjustments rhythm will be at the indiscretion of the psychiatrist. If at the end of the 6 first visits (M1 to M6), the target intensity couldn't be reached or in absence of a satisfying clinical response, a visit will be planned every 3 months (consultation or hospitalization) to keep optimizing the VNS.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Vagus Nerve Stimulation (VNS) + Best Medical Treatment (BMT)
Along with the Optimal Medical Treatment for resistant depression, the VNS + BMT arm will be implanted a medical device of VNS.
Vagus Nerve Stimulation (VNS)
The surgical intervention for the implantation of the VNS medical device is performed by a neurosurgeon under general anesthesia and lasts about an hour. Two incisions are made on the left: one incision to implant an electrode wrapped around the vagus nerve, the other incision to implant the stimulator. The electrode and the stimulator are connected by a cable tunneled. The cardiac tolerance is usually tested at the end of the surgery by turning on the neurostimulator for a few minutes. The stimulator is turned on about two weeks after the implantation, and after the neurosurgeon has checked the quality of healing. The settings used in first intention are standardized and derived from the parameters usually used for the treatment of epilepsies: a pulse width of 250μs, a stimulation frequency of 30Hz, and a 30sec stimulation cycle (ON) every 5min (OFF). Intensity is progressively increased by steps of 0.25mA to reach the 1.5-2mA range, depending on stimulation-induced side effects.
Best Medical Treatment
The BMT arm will only receive the Optimal Medical Treatment for resistant depression.
Best Medical Treatment
Best Medical Treatment for resistant depression.
Interventions
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Vagus Nerve Stimulation (VNS)
The surgical intervention for the implantation of the VNS medical device is performed by a neurosurgeon under general anesthesia and lasts about an hour. Two incisions are made on the left: one incision to implant an electrode wrapped around the vagus nerve, the other incision to implant the stimulator. The electrode and the stimulator are connected by a cable tunneled. The cardiac tolerance is usually tested at the end of the surgery by turning on the neurostimulator for a few minutes. The stimulator is turned on about two weeks after the implantation, and after the neurosurgeon has checked the quality of healing. The settings used in first intention are standardized and derived from the parameters usually used for the treatment of epilepsies: a pulse width of 250μs, a stimulation frequency of 30Hz, and a 30sec stimulation cycle (ON) every 5min (OFF). Intensity is progressively increased by steps of 0.25mA to reach the 1.5-2mA range, depending on stimulation-induced side effects.
Best Medical Treatment
Best Medical Treatment for resistant depression.
Eligibility Criteria
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Inclusion Criteria
* Childbearing women must have an efficient contraception for the whole study period
* Diagnosis of recurrent depressive trouble or persistent depressive disorder or bipolar disorder (according to DSM-5)
* Start of disorder (defined by the occurrence of the first thymus episode: characterized depressive disorder or maniac episode with or without mixed characteristics) for 5 years or more
* At least one of the following criteria:
* Criterion A: current characterized depressive disorder and characterized depressive disorder for at least 12 months during the last 24 months despite at least four treatments lines at appropriate dosage and duration
* Criterion B: current treatment by ECT and criteria A before the start of the ECT treatment or ECT dependency criteria
* Patients who, after the nature of the study has been explained to them, have given written consent
Exclusion Criteria
* Schizophrenia, schizoaffective disorder or persistent delusional disorder (DSM-5)
* Characterized depressive disorder with psychotic characteristics within 3 months before the inclusion (DSM-5)
* Concomitant participation to another interventional clinical trial, excepted eventual ancillary researches validated by the study scientific committee. Participation to non-interventional researches is allowed.
* Patients receiving enforced cares (ASPDT, ASPPI, ASPDRE, etc.)
* Non-affiliation to a social security regimen or any other social protection regimen
* Disability, according to the investigator, to understand the study or refusal to sign the study consent form (non-francophone patient, cognitive disorders)
* Anticipated disability to attend all the visits, treatments and measures planned by the protocol: severe personality disorder, severe substance addiction, severe intellectual development disorder. In any of those cases, the notion of severity is at the indiscretion of the investigator
* Surgical contraindication to the VNS
* Positive β-HCG (results obtained after the informed consent is signed but before the randomization)
18 Years
ALL
No
Sponsors
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LivaNova
INDUSTRY
Assistance Publique - Hôpitaux de Paris
OTHER
Responsible Party
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Principal Investigators
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Philippe DOMENECH, MD, MSc
Role: STUDY_DIRECTOR
GHU Paris Psychiatrie & Neurosciences (site Sainte-Anne)
Locations
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CHU Angers
Angers, , France
Centre Hospitalier Charles Perrens
Bordeaux, , France
CHU Caen
Caen, , France
CHU Clermont-Ferrand, Hôpital Gabriel Montpied
Clermont-Ferrand, , France
AP-HP. Nord - Université de Paris, Hôpital Louis Mourier
Colombes, , France
APHP. Hôpitaux Universitaires Henri Mondor, Hôpital Henri Mondor
Créteil, , France
CHU Dijon, Hôpital Le Bocage
Dijon, , France
CHU Grenoble Alpes
Grenoble, , France
AP-HP. Centre - Université de Paris, Hôpital Corentin-Celton
Issy-les-Moulineaux, , France
AP-HP. Université Paris Saclay, Hôpital Bicêtre
Le Kremlin-Bicêtre, , France
CHU Lille
Lille, , France
Hospices Civils de Lyon, Hôpital Pierre Wertheimer
Lyon, , France
Assistance Publique Hôpitaux de Marseille, Hôpital de la Conception
Marseille, , France
CHU de Nantes, Hôtel Dieu
Nantes, , France
CHU Nice, Hôpital Pasteur 1
Nice, , France
AP-HP. Sorbonne Université, Hôpital La Pitié Salpetrière
Paris, , France
GHU Paris Psychiatrie & Neuroscience, site Saint Anne
Paris, , France
Centre Hospitalier Henri Laborit
Poitiers, , France
Centre Hospitalier Guillaume Regnier
Rennes, , France
CHU Rouen, Centre Hospitalier du Rouvray
Rouen, , France
CHU Saint-Etienne
Saint-Etienne, , France
CHU Toulouse, Hôpital de Psychiatrie
Toulouse, , France
CHRU Tours, Clinique Psychiatrique Universitaire
Tours, , France
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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APHP200066
Identifier Type: -
Identifier Source: org_study_id
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