Deep Brain Stimulation to Relieve Depression (DRIVER)
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|ClinicalTrials.gov Identifier: NCT02889250|
Recruitment Status : Not yet recruiting
First Posted : September 5, 2016
Last Update Posted : October 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Treatment Resistant Depression||Device: Medtronic Activa SC DBS, Lead Model 3387||Phase 3|
Late-life treatment resistant depression (LL-TRD) is a public health and clinical dilemma.
Older patients with TRD are: 1) at greater risk for morbidity from medications and ECT, and 2) more likely to require maintenance ECT (which carries risks of cognitive impairment and repeated exposure to general anesthesia), compared to younger depressed patients. There is great need to develop targeted and safe treatments for those with LLTRD.
Deep brain stimulation (DBS) is a neurosurgical intervention with potential to become a treatment option for appropriately selected patients with LL-TRD. To date, the subcallosal cingulate white matter (SCCWM) is the DBS target with the most clinical, safety, and neurophysiologic data supporting therapeutic efficacy. The SCC is considered a "governor" for a network implicated in the processing of negative emotions and symptoms of depression. Furthermore, structural and functional impairments of the SCC and connected network structures are associated with LLD, supporting its potential as a target for DBS in older adults.
The overarching aim for this project is to develop DBS of the SCCWM for LL-TRD using an experimental medicine approach in which the investigators will program the device based both on 1) a neurophysiologic measure of target engagement and 2) safety (defined as lack of neuropsychiatric worsening and stable neurocognition). The proposed biomarker of target engagement is theta cordance (TC), a composite of absolute and relative theta power that is strongly correlated with regional neural metabolism. The hypothesis is that TC will increase during DBS is based on the observation of increased frontal TC during DBS in combination with PET data, which showed increased metabolism in frontal cortical structures in responders to DBS.
The investigators will use magnetoencephalography to measure TC during DBS and then will adjust stimulation settings to optimize target engagement over the course of the study, in response to observed increases in TC. Adding to the novelty of the project is use of personalized tractography to guide precise electrode placement in the area of the SCCWM which contain white matter tracts to mood-relevant frontal and subcortical nuclei.
During the two years of this open-label project the investigators will implant 6 patients. For each subject, over the course of 6 months, the investigators will ascertain the dose range effect of escalating DBS stimulation parameters on both TC and measures of safety.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Deep Brain Stimulation to Relieve Depression|
|Estimated Study Start Date :||June 2018|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||March 2020|
Experimental: Open Label DBS
6 months of DBS
Device: Medtronic Activa SC DBS, Lead Model 3387
Deep Brain Stimulation
- Theta cordance, measured by magnetoencephalography. [ Time Frame: 6 months ]Theta cordance combines complementary information from absolute (the amount of power in the theta oscillatory band and relative power (the percentage of power contained in the theta band relative to the total spectrum) of EEG spectra.
- Symptoms of Depression [ Time Frame: 6 months ]A measure of safety is that the stimulation does not worsen depression. Significant worsening of depressive symptoms is defined as >/= 30% worsening of symptoms, as measured with the Montgomery Asberg Depression Rating Scale (MADRS) for four consecutive weeks, compared to the average score of the 4 weeks pre-stimulation.
- Suicidality [ Time Frame: 6 months ]A measure of safety is that the stimulation does not worsen or cause suicidal ideation or behavior. The Columbia Suicide Severity Rating Scale will assess suicidality. Clinically significant suicidality is defined as greater than 3 on suicidal ideation subscale of the Columbia Suicide Severity Scale AND worsening of the score compared to baseline, OR any suicidal behavior noted on the suicidal behavior subscale.
- Neurocognitive status [ Time Frame: 6 months ]A measure of safety is that the stimulation does not worsen neurocognition. The investigators will use a comprehensive validated battery of neuropsychiatric tests to monitor change in memory, executive functioning, psychomotor speed, verbal ability and global cognitive functioning. Clinically significant worsening is defined as deterioration of > 1 SD in at least two cognitive domains after six months of stimulation, compared to pre-surgical testing.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02889250
|Contact: Jordan F. Karp, MDemail@example.com|
|Contact: Sunita Chickering, MAfirstname.lastname@example.org|