Hypothesis: 5 day multi daily neuronavigated Theta burst sessions (developed by Stanford University and coined, SNT, i.e. Stanford NeuromdulaTion protocol) are more (cost-) effective than standard 10 Hz rTMS in patients with treatment resistant…
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical outcome is remission, which is defined as a score of 7 or lower on the
clinician-rated HDRS-17 (Hamilton Depression rating Scale) measured directly
after the last treatment session.
Secondary outcome
1) Health-related quality of life determined with the EuroQol-5D13 and Health
care usage/costs, patients' and their family's out-of-pocket costs, and
productivity losses owing to absenteeism measured with the Trimbos Institute
and iMTA Cost questionnaire for Psychiatry (14).
2) Patient-reported outcome measures, i.e., positive mental health as measured
with Mental Health Continuum-Short Form (15).
3) Percentual reduction of depressive symptoms as measured with self-rated
HDRS-6 on each treatment day.
4) Relapse, at 5-, 10- and 25-weeks post-treatment. Relapse is defined as a
HDRS-17 total score of 15 or higher for 2 consecutive assessments separated by
5 to 15 days or hospitalization for depression
5) Tolerability and safety of SNT and rTMS.
6) Factors that influence the implementation of SNT that are healthcare
system-, clinician- or patient- related, in order to develop an implementation
plan.
Background summary
Novel therapies are necessary for patients with unipolar depression since more
than 35% of these patients are medication-resistant. As a consequence, there is
a high burden of illness for patients with depression*leading to increased
suicide rates, inability to maintain proper work and/or social role functions,
and reduced quality of life. A possible novel treatment strategy is an
intensive five day course of intermittent Theta Burst, a form of transcranial
magnetic stimulation (rTMS), which could lead to extremely high remission rates
(79%) in patients with treatment resistant depression. However, it remains
unknown whether this novel treatment strategy could be effective in depressed
patients when compared to standard 10Hz rTMS (remission 30%).
Study objective
Hypothesis: 5 day multi daily neuronavigated Theta burst sessions (developed by
Stanford University and coined, SNT, i.e. Stanford NeuromdulaTion protocol) are
more (cost-) effective than standard 10 Hz rTMS in patients with treatment
resistant depression.
Objective: To determine remission of depression and cost effectiveness using
the SNT protocol, in patients with treatment resistant depression who did not
respond to two or more evidence-based treatments.
Study design
This study comprises a multicentre, two-phase, randomized clinical trial. Phase
1 comprises a randomized controlled trial. In Phase 1, participants will be
assigned to one of the two active treatment conditions, and will receive either
treatment using the SNT protocol (5 days of 10 sessions/day, resulting in 50
sessions in total 90000 pulses) or standard 10 Hz left sided rTMS, provided
once daily during 6 weeks (30 sessions in total, 90000 pulses). Phase 2
comprises three follow-up measurements, one at 5 weeks, one at 10 weeks and one
at 25 weeks after the last treatment with SNT or 10 Hz standard rTMS. Finally,
participants who were allocated to standard 10 Hz rTMS will be offered SNT
after the end of the study (e.g. 25 weeks after the last rTMS session).
Patients allocated to SNT can obtain 10 Hz standard rTMS after SNT has been
completed.
Intervention
Intervention: 50 sessions using the SNT protocol in 5 days. We will target the
region of the left DLPFC most anticorrelated with the subgenual anterior
cingulate cortex (sgACC) in each participant based on subject-specific
functional resting state MRI.
Comparison: 30 standard daily 10 Hz rTMS sessions in six weeks, targeting the
left DLPFC based on standard measurement procedures of the skull.
Study burden and risks
Benefits: Possible increased remission compared to standard 10 Hz rTMS in
patients with treatment resistant depression using the SNT protocol (average
remission of 79% based on two small open label studies and a small RCT vs 30%
remission in those receiving standard 10 Hz rTMS). We will also offer SNT after
25 weeks of follow-up, to participants who received standard 10 Hz rTMS.
Knowledge gained from this study will allow adequate positioning of a possible
novel treatment in the algorithm to treat patients with depression.
Burden and feasibility: The total time for study measurements for the
participants allocated to SNT will be (180 plus 145 plus 3x 45) 460 minutes
versus (180 plus 150 plus 3x45) 465 minutes for the participants allocated to
standard 10 Hz rTMS. The total treatment time will be 5 days of 10 hours for
the participants allocated to SNT and 6 weeks of daily (30 minute) sessions for
the participants allocated to standard 10 Hz rTMS. Despite the high investment
of patients, earlier studies have shown that an RCT, with rTMS is feasible with
a drop out of approximately 7%.
Risk: rTMS and ITBS are proven safe treatments. rTMS and iTBS are widely used
non-invasive brain stimulation technique, based on the principle of
electromagnetic induction. During stimulation the participant will likely hear
the clicks of the TMS pulses and experience stimulation of nerves and muscles
of the head. The most common side effect is a light transient headache (~10%
occurrence). A severe headache is uncommon (0.3-0.5% occurrence). In the
current study patients will be stimulated with treatment a protocols that fall
within the safety guidelines. All participants are screened for their relevant
medical history and other TMS/iTBS safety aspects (e.g. presence of metal parts
in the head).
Benefits: In this study, there will bet least the normal expected clinical
benefit resulting in at least 25% remission for those receiving standard 10 Hz
rTMS, whereas it is likely that remission in the SNT group is higher, and at
least equal to the 25% remission for standard 10 Hz rTMS.
Boelelaan 1117
Amsterdam 1081 HX
NL
Boelelaan 1117
Amsterdam 1081 HX
NL
Listed location countries
Age
Inclusion criteria
Adult patients with unipolar depression who did not respond to two or more
evidence-based treatments for depression, in the current depressive episode,
aged 18 years and over. In order to be eligible to participate in this study, a
participant must meet all following criteria: - 18 years of age or older; -
Sufficient level of spoken and written Dutch; - Ability to freely provide
written informed consent; - Current DSM-5 diagnosis of a depressive episode,
ascertained by the Mini International Neuropsychiatry Interview (MINI-S). - A
Hamilton depression rating score (HDRS) of >16 points - have a treatment
resistant depression, defined according to the criteria of Conway, that is,
lack of remission for eight consecutive weeks after two different
evidence-based treatments anti-depressant medication has to be adequately
dosed. - Stable anti-depressant medication 6 weeks prior to study.
Benzodiazepines may be used up to a dosage equivalent of 3.0 mg lorazepam, and
can be lowered over time during the study based on clinical judgement.
Exclusion criteria
Participants meeting any of the following criteria will be excluded from
participation in this study - Bipolar disorder. - Current psychotic disorder*
including psychotic depression, assessed by treating psychiatrist. - Suspected
dementia, assessed with a dementia screening tool, i.e.i.e., the Montreal
Cognitive Assessment (MOCA)(31), with a score of less than 20 points, or a
clinical suspicion of dementia, or neuroimaging indication for
neurodegeneration with a Fazekas > 1 and MTA >1. These cut-offs ensure
exclusion of patients with (preclinical) dementia. - Active suicidal thoughts
and intent to act on it, assessed at the baseline interview and before the
start of the trial. This assessment is based on the Columbia suicide severity
rating scale, i.e.i.e., question 5 is answered positive *Have you started to
work out or worked out the details of how to kill yourself? Do you intend to
carry out this plan?* (32). - Metallic devices implanted above the neck,
assessed at the baseline interview. - Patients diagnosed with epilepsy, by a
neurologist, assessed at the baseline interview. - Substance abuse 4 weeks
prior to the study, including high dosage of benzodiazepine, a dosage
equivalent higher than 3.0 mg lorazepam, assessed at the baseline interview. -
Inability to understand or comply with study requirements as judged by the
investigators, assessed at the baseline interview. - 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 | NL83892.018.23 |