Clinical trial NCT01372722: Deep Brain Stimulation (DBS) for Treatment Resistant Bipolar Disorder
Official title: Phase I Study of Bilateral DBS to the Nucleus Accumbens (NAcc-DBS) for Treatment Resistant Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Bipolar Disorder
Keywords: treatment resistant
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2011-06-14
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Hypothesis to be tested:

Bilateral Deep Brain Stimulation to the Nucleus Accumbens is associated with clinically and statistically significant improvement in patients with treatment resistant bipolar disorder.

Overall Objective:

The aim in this interdisciplinary, psychiatric-neurosurgical project is to evaluate safety and efficacy of bilateral Deep Brain Stimulation to the Nucleus Accumbens (NAcc) using the Medtronic Activa RC Neurostimulator in patients with treatment resistant Bipolar Disorder.


Eligibility criteria: Inclusion Criteria:

* Age 20-70 years old. • German mother tongue • Ability to provide written informed consent.
* At least one manic or hypomanic episode according to DSM IV previous to onset of last depressive episode.
* Global Assessment of Function (GAF) score of \> 46 • 5 years after the first episode of MD • DSM IV criteria for a current Major Depressive Episode (MDE) diagnosed by structured clinical interview for DSM IV. Diagnosis will be confirmed by two independent psychiatrists. • Current episode of MD \> two years duration OR a history of more than 4 lifetime depressive episodes. • Minimum score at study entry of 28 on the 24-item Hamilton Depression Rating Scale (HDRS24).
* Average pre-operative HDRS24 score of 28 or greater (averaged over screening period) and a final preoperative HDRS24 score no more than 30% lower than the baseline screening HDRS score. • Treatment-resistant depression defined as: • Failure to respond to a minimum of four different antidepressant treatments, including medications and evidence-based psychotherapy (\> 20 sessions with an experienced psychotherapist) administered at adequate doses and duration during the current episode. We will require documentation (i.e., statement from the treating psychiatrist) that a treatment trial has failed (either no response to maximum tolerable doses for a minimum of 5 weeks, or side-effects at sub-maximal doses) as coded by the Antidepressant Treatment History Form (ATHF). The study investigators will document each treatment by way of review of records from referring psychiatrists. • Failure or intolerance of an adequate course of electroconvulsive therapy (ECT) during any episode (\> 6 bilateral treatments).
* A patient may remain on psychotropic medications during this study. However, doses must remain stable during a one month pre-operative evaluation period, the single blind phase and the open stimulation phase.

-If currently in psychotherapy, a patient must have been in this therapy for at least six months and continue to attend scheduled visits at no greater or lesser frequency than during the last three months. -

* Patients must have an established outpatient psychiatrist.
* Patients are able to fulfill the study requirements.
* Patients are in good general health.

Exclusion Criteria:

* Inability to tolerate general anesthesia.
* 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)
* Cerebrovascular risk factors or a previous stroke, documented head trauma or neurodegenerative disorders.
* Other clinically significant Axis I psychiatric diagnoses including schizophrenia, bipolar I disorder (patients with bipolar II disorder will be included), panic disorder, obsessive-compulsive disorder, generalized anxiety disorder or post-traumatic stress disorder in the previous 12 months. Patients with severe Axis II personality disorders will also be excluded if they have the potential to interfere with cooperation during the pre- and post-operative phases of the study.
* Current psychotic symptoms.
* Current mixed episode.
* Evidence of global cognitive impairment.
* Substance abuse or dependence within the last year (except nicotine).
* Active suicidal ideation.
* Pregnancy and women of childbearing age not using effective contraception or currently nursing.
* General contraindications for DBS surgery (impossibility to conduct pre-operative fMRI, infections, claustrophobia, pregnancy, impossibility to stay awake during electrode implantation, medical risks regarding the operation, cardiac pacemaker/defibrillator or other implanted devices).
* Inability or unwillingness to comply with long-term follow-up.
* Patients who are not able to read and understand the consent form, or who are not capable of understanding or giving informed consent to the procedures of the study.
* History of intolerance to stimulation of any area of the body
* Participation in another drug, device or biologics trial within the preceding 30 days.
* Conditions requiring repeated MRI scans
* Conditions requiring diathermy
* Conditions requiring anticoagulant medication

Primary outcomes:
measure: Depression Severity rated with Montgomery Asberg Depression Scale (MADRS)
timeFrame: 12 month after DBS stimulation onset
measure: Young Mania Rating Scale (YMRS)
timeFrame: 12 month after DBS stimulation onset
Secondary outcomes:
measure: Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)
timeFrame: 12 month after DBS stimulation onset
measure: Adverse Event Schedule
timeFrame: 12 month after DBS stimulation onset
measure: Comprehensive neuropsychological test battery
timeFrame: 12 month after DBS stimulation onset
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Department of Psychiatry and Psychotherapy - University Hospital
Study officials:
References: