Treatment Resistant Depression and Vagus Nerve Stimulation

NCT05952674 | Recruiting DMC

• 1 other identifier: APHP200066
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 23

Brief Summary

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.

Conditions

Treatment Resistant Depression (TRD)

Keywords

Treatment Resistant Depression (TRD); Vagus Nerve Stimulation (VNS); Best Medical Treatment (BMT)

Outcome Measures

Primary Outcomes (1)

• Cost-utility of VNS

  Incremental cost-utility ratio of the Vagus Nerve Stimulation (group VNS + optimal medical treatment) in comparison to the control group (optimal medical treatment only) within 24 months of VNS placement

  Month 24

Secondary Outcomes (37)

• Efficacy of the VNS

  Month 24

• Efficacy of the VNS

  Month 24

• Efficacy of the VNS

  Month 24

• Efficacy of the VNS

  Month 24

• Efficacy of the VNS

  Months: 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24

Study Arms (2)

Vagus Nerve Stimulation (VNS) + Best Medical Treatment (BMT)

EXPERIMENTAL

Along with the Optimal Medical Treatment for resistant depression, the VNS + BMT arm will be implanted a medical device of VNS.

Device: Vagus Nerve Stimulation (VNS)

Best Medical Treatment

ACTIVE COMPARATOR

The BMT arm will only receive the Optimal Medical Treatment for resistant depression.

Other: Best Medical Treatment

Interventions

Vagus Nerve Stimulation (VNS) DEVICE

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.

Vagus Nerve Stimulation (VNS) + Best Medical Treatment (BMT)

Best Medical Treatment OTHER

Best Medical Treatment for resistant depression.

Best Medical Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• Know pregnancy or breastfeeding
• Schizophrenia, schizoaffective disorder or persistent delusional disorder (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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• LivaNova: collaborator

Study Sites (23)

CHU Angers

Angers, 49933, France

ACTIVE NOT RECRUITING

Centre Hospitalier Charles Perrens

Bordeaux, 33076, France

RECRUITING

CHU Caen

Caen, 14000, France

NOT YET RECRUITING

CHU Clermont-Ferrand, Hôpital Gabriel Montpied

Clermont-Ferrand, 63000, France

RECRUITING

AP-HP. Nord - Université de Paris, Hôpital Louis Mourier

Colombes, 92700, France

WITHDRAWN

APHP. Hôpitaux Universitaires Henri Mondor, Hôpital Henri Mondor

Créteil, 94000, France

NOT YET RECRUITING

CHU Dijon, Hôpital Le Bocage

Dijon, 21000, France

RECRUITING

CHU Grenoble Alpes

Grenoble, 38700, France

RECRUITING

AP-HP. Centre - Université de Paris, Hôpital Corentin-Celton

Issy-les-Moulineaux, France

WITHDRAWN

AP-HP. Université Paris Saclay, Hôpital Bicêtre

Le Kremlin-Bicêtre, 94270, France

WITHDRAWN

CHU Lille

Lille, 59037, France

RECRUITING

Hospices Civils de Lyon, Hôpital Pierre Wertheimer

Lyon, 69677, France

NOT YET RECRUITING

Assistance Publique Hôpitaux de Marseille, Hôpital de la Conception

Marseille, 13005, France

NOT YET RECRUITING

CHU de Nantes, Hôtel Dieu

Nantes, 44093, France

RECRUITING

CHU Nice, Hôpital Pasteur 1

Nice, 06001, France

RECRUITING

AP-HP. Sorbonne Université, Hôpital La Pitié Salpetrière

Paris, 75013, France

ACTIVE NOT RECRUITING

GHU Paris Psychiatrie & Neuroscience, site Saint Anne

Paris, 75014, France

RECRUITING

Centre Hospitalier Henri Laborit

Poitiers, 86021, France

NOT YET RECRUITING

Centre Hospitalier Guillaume Regnier

Rennes, 35703, France

NOT YET RECRUITING

CHU Rouen, Centre Hospitalier du Rouvray

Rouen, 76300, France

RECRUITING

CHU Saint-Etienne

Saint-Etienne, 42055, France

RECRUITING

CHU Toulouse, Hôpital de Psychiatrie

Toulouse, 31059, France

RECRUITING

CHRU Tours, Clinique Psychiatrique Universitaire

Tours, 37540, France

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Vagus Nerve Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Officials

• Philippe DOMENECH, MD, MSc

  GHU Paris Psychiatrie & Neurosciences (site Sainte-Anne)

  STUDY DIRECTOR

Central Study Contacts

Philippe DOMENECH, MD, MSc

CONTACT

(0) 1 45 65 76 65; philippe.domenech@ghu-paris.fr

Fabien VINCKIER, MD, MSc

CONTACT

(0) 1 45 65 84 52; f.vinckier@ghu-paris.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: None of the parties involved in this research will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Best Medical Treatment only (BMT arm).

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: July 19, 2023
• Study Start: September 19, 2024
• Primary Completion (Estimated): August 26, 2028
• Study Completion (Estimated): August 19, 2030
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (23)