Establishing efficacy of MFB DBS for TRD by comparing active DBS with sham DBS. Secondary aims are establishing an adverse events profile, establishing effects on quality of life, cost-effectiveness, (neuro)psychological and neuroimaging measures.
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in scores between active and sham DBS on the Hamilton Depression
Rating Scale, 17 items (HAM-D-17, range 0-52 with higher scores indicating more
symptoms);
Secondary outcome
Percentage of responders after the open label phase (defined as a >=50%
reduction of the baseline HAM-D-17 score).
Change over time of HAM-D score, MADRS score, and IDS-SR score.
Adverse events.
Change of cognitive functions (measured with neuropsychological tests), quality
of life (using questionnaires), personality (using questionnaires), brain
activity (MRI scans), and physical functioning.
Acute changes before and after turning on DBS (measured with a diary).
Background summary
Multiple open-label studies have shown approximately 40% of treatment-resistant
depressed patients to respond to deep brain stimulation (DBS) of the ventral
striatum and surrounding capsula. Recent pilot studies show efficacy of deep
brain stimulation (DBS) in patients with depression is dependent on the
distance of the electrode to a specific brain bundle: the medial forebrain
bundle (MFB).
Study objective
Establishing efficacy of MFB DBS for TRD by comparing active DBS with sham DBS.
Secondary aims are establishing an adverse events profile, establishing effects
on quality of life, cost-effectiveness, (neuro)psychological and neuroimaging
measures.
Study design
24 patients are included in a longitudinal, open-label study, followed by a
double blind, randomized crossover trial. All patients recieve open-label DBS
for the first 6 months, during which DBS parameters are optimized.
Subsequently, patiens are randomized to 1 week of active DBS, followed by 1
week of placebo DBS, or vice versa. A washout phase of 4 (+/- 1) weeks between
the two phase is implemented to prevent carry-over effects. After the crossover
phase, patients are followed up for one year in an open-label fashion.
24 healthy controls are tested 3 times: at baseline, after 6 and after 18
months to control for aspecific or practice effects over time.
Intervention
DBS targeted to the MFB. After the open-label phase patients are randomized to
active DBS followed by sham DBS, or vice versa.
Study burden and risks
Over a period of 1.5 years, patients need to visit the hospital nine times:
once for screening, and eight times for study visits. All visits take 1-4
hours, and the full protocol takes approximately 26 hours. For the treatment,
the patient needs to undergo surgery, for which the patients needs to be
admitted to the neurosurgery department for 3 days. For the optimization of the
treamtent, the patients is admitted at the Psychiatry ward for 2-5 days, after
which the patient needs to visit the outpatient clinic approximately 5-15
times. We estimate the benefits outweigh the risks of the treatment. First,
patients can have a direct clinical benefit from participation. Second, risks
are judged to be moderate and monitored closely by experienced teams of
psychiatrists, neurosurgeons, psychologists and specialized nurses. In case of
suspected risk of harm for the patient, we can admit patients to our clinic. In
addition, the study in its entirety is monitored by in-house monitors, as well
as a Data Safety Monitoring Board (DSMB).
Healthy controls need to visit the hospital 4 times for neuropsychological
tests and MRI scans. All visits take approximately 1-4 hours, and the full
protocol takes approximately 10 hours.
Meibergdreef 5
Amsterdam 1105 AZ
NL
Meibergdreef 5
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1) Primary diagnosis: Major Depressive Disorder
2) Treatment-resistance defined as inadequate response to (or intolerable side
effects) of all of the following:
a. At least 2 adequately dosed treatments of at least two 2nd generation
antidepressants (SSRI, SNRI, NaSSA) for a period of 6-8 weeks
b. An adequately dosed treatment with a tricyclic antidepressant (TCA) for 6-8
weeks
c. TCA + addition of lithium when tolerable at least 6 weeks at therapeutic
drug levels (>0.6 mmol/L))
d. An adequately dosed treatment with a monoamine oxidase inhibitor OR >=1
session of ECT, for which the series of ECT was terminated either due to
adverse effects or insufficient response (including at least 6 sessions of
bilateral ECT) OR patients who are kept stable with maintenance ECT, but who
relapse after discontinuation of this maintenance ECT are also eligible, but
need to fulfill all other inclusion criteria.
Besides the above defined treatments, we will evaluate the adequacy of all
attempted antidepressant treatments, including off-label strategies such as
esketamine. In case on- or off-label treatments are available to the patient,
but have not been tried adequately, these options are discussed with and
offered to the patient before offering deep brain stimulation.
3) HAM-D total >= 18
4) Illness duration > 2 years
5) Age: 20-75 years old
Exclusion criteria
1) Bipolar Disorder
2) Schizophrenia /history of psychosis unrelated to MDD
3) Alcohol or substance abuse (including benzodiazepines) during last 6 months,
excluding nicotine use
4) Primary and severe personality disorder diagnosed independently from TRD
5) Explicit suicidal plans requiring hospitalization in a closed ward
6) Contraindications to have surgery
7) Depression as a result of acute brain damage (e.g. stroke / hemorrhage)
8) Parkinson*s disease, Tourette syndrome, dementia, epilepsy, tic disorder
9) Pregnancy
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71221.018.19 |
| Other | NL8211 |