Recruiting NCT05952674

Treatment Resistant Depression and Vagus Nerve Stimulation

No phase Interventional Treatment Resistant Depression (TRD)

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Vagus Nerve Stimulation (VNS), Best Medical Treatment.
Who it may be relevant to: Registry conditions: Treatment Resistant Depression (TRD). Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: France
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Resistant Depression and Vagus Nerve Stimulation : a Medico-economic, Multicenter, Randomized and Open Trial

Overview

Depression is a common illness, affecting 17% of the population over the course of a lifetime. A third of depressions relapses and progresses to recurrence and resistance to treatments. Despite the optimization of antidepressant medical strategies, 20 to 40% of depressions do not respond to treatment. This is particularly worrying as 6% of non-responder patients will die by committing suicide. 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.

Detailed description

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.

Interventions

Device 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 stim
Other Best Medical Treatment
Best Medical Treatment for resistant depression.

Primary outcome measures

Cost-utility of VNS [Time frame: Month 24]

Secondary outcome measures (12)

Efficacy of the VNS [Time frame: Month 24]
Efficacy of the VNS [Time frame: Month 24]
Efficacy of the VNS [Time frame: Month 24]
Efficacy of the VNS [Time frame: Month 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]
Efficacy of the VNS [Time frame: Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24]

Eligibility criteria

Inclusion criteria

Patients aged 18 years and older ;
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/(Es)Ketamine/TMS and criteria A before the start treatment or ECT/(Es)Ketamine/TMS dependency
Patients who, after the nature of the study has been explained to them, have given written consent

Exclusion criteria

Know pregnancy or breastfeeding
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 research not authorized by the coordinating investigator or the scientific lead. 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

Secondary Exclusion Criteria:

Surgical contraindication to the VNS
Positive β-HCG (results obtained after the informed consent is signed but before the randomization)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment

Study locations

France · 24 centers

CHU Angers — Angers
Centre Hospitalier Charles Perrens — Bordeaux
CHU Caen — Caen
CHU Clermont-Ferrand, Hôpital Gabriel Montpied — Clermont-Ferrand
AP-HP. Nord - Université de Paris, Hôpital Louis Mourier — Colombes
APHP. Hôpitaux Universitaires Henri Mondor, Hôpital Henri Mondor — Créteil
CHU Dijon, Hôpital Le Bocage — Dijon
CHU Grenoble Alpes — Grenoble
… and 16 more centers

Identifiers

NCT: NCT05952674 · APHP200066

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗