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Treatment-resistant DepressionFORESEE IIINCT03653858

Efficacy Study of Deep Brain Stimulation in Patients With Treatment Resistant Major Depression

A study testing Vercise GEVIA deep brain stimulation (DBS) system in people with Treatment-resistant Depression, run by University Hospital Freiburg at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of this multicenter, randomized, sham-controlled, double blind (patient and observer blinded) clinical trial is to assess the antidepressant effect of Deep Brain Stimulation (DBS) in patients with treatment resistant major depression using the Boston Scientific implantable Vercise™ GEVIA™ DBS… Read more about this study

Who is it for?
Ages 20 to 75 years
Conditions the study is for
Treatment-resistant Depression
What is being tested?
Vercise GEVIA deep brain stimulation (DBS) system
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
2 sitesin 2 countries
Study dates
3 Sep 2018to 7 Jan 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Major depression (MD), severe, unipolar, or bipolar in an acute depression episode.
  • German mother tongue or fluent.
  • Male or female patients ≥20 and ≤75 years.
  • Hamilton Depression Rating Scale (HDRS-28) score of >21.
  • Global Assessment of Function (GAF) score of <45.
  • At least 4 episodes of depression or one chronic episode >2 years.
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  • Failure to respond to
  • adequate trials of primary antidepressants from at least 3 different classes (>5 weeks at the maximum recommended or tolerated dose) and
  • adequate trials of augmentation/combination of a primary antidepressant (>3 weeks at the usually recommended or maximum tolerated dose) using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) and
  • an adequate trial of electroconvulsive therapy (ECT) (>6 treatments) and an adequate trial of individual psychotherapy (>20 sessions with an experienced psychotherapist).
  • Able to give written informed consent.
  • Compliance to participate in the study.
  • Drug free or on stable drug regimen at least 6 weeks before study entry.

Who cannot join

  • Current or past non-affective psychotic disorder.
  • Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome.
  • Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI), any contraindications to perform a planned MRI to visualize the slMFB.
  • Any surgical contraindications to undergoing DBS like deformed or displaced or not discernable target region, scarring after brain disease (infarction), need for continuous anticoagulation that cannot be bridged in order to obtain normal coagulation, present risks for anesthesia or any brain or scalp injury (even after intracranial surgery).
  • Current or unstably remitted substance abuse (aside from nicotine).
  • Pregnancy, women of childbearing age not using effective contraception and breast feeding women.
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  • History of severe personality disorder.
  • Acute suicidal ideation.
  • Patients with advanced stage cardiovascular disease.
  • Patients under immunosuppressive or chemo therapy because of malignant disease.
  • Patients who had previous intracranial surgery.
  • Patients who are currently under DBS therapy or have implanted any kind of stimulator already.
  • Patients with aneurysm clips.
  • Patients with cochlear implants.
  • Patients with planned diathermy.
  • Persons who are in a relationship of dependence/employment with the sponsor or the investigator.
  • Simultaneous participation or previous participation within 30 days prior to start of screening in a clinical trial involving investigational medicinal product(s) or investigational medical device(s).

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

France1 site

  • Université Grenoble Alpes

    Grenoble, 38043

Other trials in France

Germany1 site

  • University Hospital Freiburg

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

Other trials in Germany

About this study

Official title: Controlled Randomized Clinical Trial to Assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients With Treatment Resistant Major Depression

The primary objective of this multicenter, randomized, sham-controlled, double blind (patient and observer blinded) clinical trial is to assess the antidepressant effect of Deep Brain Stimulation (DBS) in patients with treatment resistant major depression using the Boston Scientific implantable Vercise™ GEVIA™ DBS system compared to sham.

Read the detailed description

The main objective of this clinical trial is to assess the putative antidepressant efficacy of a therapeutic method called Deep Brain Stimulation (DBS) in patients suffering from severe, treatment-resistant depression, i.e. in patients who have not sufficiently improved under established antidepressant therapies (such as psychotherapy, antidepressant drug therapy, and electroconvulsive therapy).

DBS, also known as "brain pacemaker" therapy, is a neurosurgical therapeutic method that is widely established for the treatment of other conditions such as Parkinson's disease. However, DBS is not yet approved for the treatment of patients with depression.

In order to initiate DBS treatment, a neurosurgical procedure is performed in which electrodes are placed in a brain region termed 'medial forebrain bundle' (MFB). The electrodes are then used to stimulate this region with electric pulses. From previous investigations and studies with small numbers of patients, it is believed that DBS might have a positive effect on depressive symptoms in patients treated with the method.

Being tested
Vercise GEVIA deep brain stimulation (DBS) system
Keywords
Deep Brain Stimulation, Treatment-resistant depression, Medial forebrain bundle
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vercise GEVIA deep brain stimulation (DBS) systemDevice

    DBS to the superolateral branch of the Medial Forebrain Bundle (slMFB)

Study groups in NCT03653858
Study groupRoleWhat they receive
Group A: DBS onset in week 1ExperimentalImplantation of Vercise GEVIA deep brain stimulation (DBS) system. DBS onset in week 1. 2ND STAGE: After 6 months DBS ON, patients will be assessed whether they are responders or non-responders. In the subgroup of eligible responders, patients will be randomized to either DBS OFF* (for max. 3 months) or continued DBS for another 6 months. *DBS OFF until worsening of clinical depression, event (defined as > 5 points augmentation in MADRS in two consecutive visits) or for a maximum of 3 months. After DBS OFF, re-onset of DBS will be performed, followed by 6 months continuous DBS. Non-responders will also receive another 6 months DBS therapy in the 2nd stage. At sites other than Freiburg/Bonn, the 2nd stage consists of 6 months DBS therapy only.
Receives: Device: Vercise GEVIA deep brain stimulation (DBS) system
Group B: DBS off, followed by DBS onset in week 17Sham comparatorImplantation of Vercise GEVIA deep brain stimulation (DBS) system. 4 months OFF after implantation followed by DBS onset in first week of month 5. 2ND STAGE: See group A.
Receives: Device: Vercise GEVIA deep brain stimulation (DBS) system

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Montgomery-Asberg Depression Rating Scale (MADRS) total score

    Primary outcome (Efficacy). MADRS is an established instrument to rate symptoms of depression. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts Each of the 10 items yields a score of 0 to 6. These item scores are summed up to yield a total score. The range of the total score is thus 0 to 60; higher total scores indicate more severe depressive symptoms.

    Usual cutoff points are:

    0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; >34 - severe depression

    Measured: 16 weeks after surgery

  2. Time to Montgomery-Asberg Depression Rating Scale (MADRS) augmentation of >5 points or clinical worsening in two consecutive visits after DBS termination

    Primary outcome in 2nd stage; Description MADRS: see above.

    Measured: Up to 3 months

  3. Assessment of (Serious) Adverse Events related to Investigational Medical Device and / or surgical procedures

    Primary outcome (Safety); (Serious) adverse events seen will be reported using standard descriptive statistical methods.

    Measured: From IMD implantation until the end of study; assessed up to 77 weeks

Secondary outcomes (46)

  1. Hamilton Depression Rating Scale (HDRS-28) total score

    HDRS is an established instrument to rate symptoms of depression. Different versions exist, using between 17 and 29 items. In this study, the 28-item version (HDRS-28) is used. The patient is rated by a clinician, items are scored either on a 3-point or 5-point Likert-type scale.

    Single item scores are summed up to yield a total score. The total score ranges from 0 to 85; a higher total score indicates more severe depressive symptoms.

    Measured: 16 weeks after surgery

  2. Clinical Global Impression Score (CGI) total score

    The CGI is a scale that measures the global severity of illness, the global improvement relative to the beginning of the study as well as the therapeutic effect and adverse reactions, score ranges from 0 to 7 for severity of illness and global improvement, a higher score indicates more severe symptoms and a worsening of symptoms; score ranges from 0 to 8 for the efficacy index, 0 means that the efficacy can't be evaluated, a score of 2 means best efficacy while a score of 8 means no therapeutic effect and more adverse reactions

    Measured: 16 weeks after surgery

  3. Global Assessment of Functioning (GAF) total score

    Score ranges from 100 (high functioning) to 1 (severly impaired)

    Measured: 16 weeks after surgery

  4. Beck Depression Inventory (BDI-II) total score

    Score ranges from 0 to 63; a higher total score indicates more severe depressive symptoms

    Measured: 16 weeks after surgery

  5. 36-Item Short Form Health Survey (SF-36) total score

    Health-related quality of life questionnaire; 8 subscales: General health perceptions, physical functioning, role limitations due to physical problems, bodily pain, vitality, general mental health, role limitations due to emotional problems, social functioning. The score in each subscale ranges from 0 to 100; subscores add up to two total scores, "physical health" and "mental health", each with a score range of 0-400. Higher scores indicate better health-related quality of life.

    Measured: 16 weeks after surgery

  6. Change over time in HDRS total score after DBS surgery with DB stimulation OFF compared to stimulation ON

    HDRS: see above

    Measured: assessed weekly for 16 weeks after surgery

  7. Change over time in CGI total score after DBS surgery with DB stimulation OFF compared to stimulation ON

    CGI: see above

    Measured: assessed weekly for 16 weeks after surgery

  8. Change over time in GAF total score after DBS surgery with DB stimulation OFF compared to stimulation ON

    GAF: see above

    Measured: assessed weekly for 16 weeks after surgery

  9. Change over time in BDI-II total score after DBS surgery with DB stimulation OFF compared to stimulation ON

    BDI-II: see above

    Measured: assessed weekly for 16 weeks after surgery

  10. Change over time in SF-36 total score after DBS surgery with DB stimulation OFF compared to stimulation ON

    SF-36: see above

    Measured: assessed weekly for 16 weeks after surgery

  11. Neuropsychological Assessments: Rey Complex Figure Test (CFT)

    Score range 0-36, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  12. Neuropsychological Assessments: d2 concentration test (d2)

    Higher scores indicate better cognitive performance (total of right answers minus errors)

    Measured: at 4 months after implantation

  13. Neuropsychological Assessments: 5-Point-Test

    Score range 0-35, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  14. Neuropsychological Assessments: Wechsler Adult Intelligence Scale (WAIS) (vocabulary, similarities)

    Score range "vocabulary": 0-32, Score range "finding similarities": 0-32, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  15. Neuropsychological Assessments: Mini-Mental-Status-Test (MMST)

    Score range 0-30, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  16. Neuropsychological Assessments: Multiple-Choice Vocabulary Intelligence Test (MWT-B)

    Score range 0-37, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  17. Neuropsychological Assessments: Rey Visual Design Learning Test (RVDLT)

    Score range 0-75, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  18. Neuropsychological Assessments: Word Fluency Test

    No maximum scores, patient has two minutes to produce answers, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  19. Neuropsychological Assessments: Stroop-Test

    Time in s, low scores (less seconds) indicate better cognitive performance

    Measured: at 4 months after implantation

  20. Neuropsychological Assessments: Test for Attentional Performance (TAP)

    Reaction times as well as correct or false responses and omissions are measured, higher cognitive performance is indicated by fast responses, few errors and high no. of correct responses

    Measured: at 4 months after implantation

  21. Neuropsychological Assessments: Trail-Making Test (TMT)

    Time in s, low scores (less seconds) indicate better cognitive performance

    Measured: at 4 months after implantation

  22. Neuropsychological Assessments: Verbal Memory and Learning Ability Test

    Score range 0-75, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  23. Neuropsychological Assessments: Hopper Visual Organization Test (VOT)

    Score range 0-30, higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  24. Neuropsychological Assessments: Digit-Span and Block-Span Test

    Score range 0-12 for each of for dimensions: Digit span forward, digit span backward, block span forward, block span backward. Higher scores indicate better cognitive performance

    Measured: at 4 months after implantation

  25. MADRS total score during long-term follow-up compared to baseline

    MADRS: see above

    Measured: at 12 months stimulation

  26. HDRS total score during long-term follow-up compared to baseline

    see above

    Measured: at 12 months stimulation

  27. CGI total score

    see above

    Measured: at 6 and 12 months DB stimulation compared to baseline

  28. GAF total score

    see above

    Measured: at 6 and 12 months DB stimulation compared to baseline

  29. BDI-II total score

    see above

    Measured: at 6 and 12 months DB stimulation compared to baseline

  30. SF-36 total score

    see above

    Measured: at 6 and 12 months DB stimulation compared to baseline

  31. Neuropsychological Assessments: Rey Complex Figure Test (CFT)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  32. Neuropsychological Assessments: d2 concentration test (d2)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  33. Neuropsychological Assessments: 5-Point-Test

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  34. Neuropsychological Assessments: Wechsler Adult Intelligence Scale (WAIS) (vocabulary, similarities)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  35. Neuropsychological Assessments: Mini-Mental-Status-Test (MMST)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  36. Neuropsychological Assessments: Multiple-Choice Vocabulary Intelligence Test (MWT-B)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  37. Neuropsychological Assessments: Rey Visual Design Learning Test (RVDLT)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  38. Neuropsychological Assessments: Word Fluency Test

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  39. Neuropsychological Assessments: Stroop-Test

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  40. Neuropsychological Assessments: Test for Attentional Performance (TAP)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  41. Neuropsychological Assessments: Trail-Making Test (TMT)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  42. Neuropsychological Assessments: Verbal Memory and Learning Ability Test

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  43. Neuropsychological Assessments: Hopper Visual Organization Test (VOT)

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  44. Neuropsychological Assessments: Digit-Span and Block-Span Test

    see above

    Measured: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks

  45. Incidence of relapse into clinical depression after tapering down of DBS

    The incidence of relapse into clinical depression after discontinuation of DBS will be assessed.

    Measured: From discontinuation of DBS until the date of first documented relapse, assessed up to 12 weeks

  46. Pattern of metabolic activity as measured by FDG-PET at 1 week and 4 months after implantation compared to baseline

    Change of metabolic activity in the prefrontal and orbitofrontal cortex as well as in subcortical regions (nucl. accumbens, amygdala) (exploratory endpoint)

    Measured: at 1 week and 4 months after implantation compared to baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start3 Sep 2018
  3. Primary completion7 Jan 2026
  4. Study completion7 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
multicenter, randomized, sham-controlled, double blind (patient and observer blinded)
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03653858
Sponsor's protocol ID
P000767
Other IDs
DRKS00014947, CIV-17-07-020746
Acronym
FORESEE III
Status last verified
Apr 2026
First submitted
22 Aug 2018
Last updated
28 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A study testing Vercise GEVIA deep brain stimulation (DBS) system in people with Treatment-resistant Depression, run by University Hospital Freiburg at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montgomery-Asberg Depression Rating Scale (MADRS) total score (time frame: 16 weeks after surgery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03653858.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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