Ignite Creation Date:
2024-05-06 @ 2:11 AM
Last Modification Date:
2024-10-26 @ 11:14 AM
Study NCT ID:
NCT01984710
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-25
First Post:
2013-09-23
Brief Title:
Deep Brain Stimulation for Treatment Resistant Depression With the Medtronic Activa PCS
Sponsor:
Emory University
Organization:
Emory University
Study Overview
Official Title:
Deep Brain Stimulation for Treatment Resistant Depression Exploration of Local Field Potentials LFP With the Medtronic Activa Primary Cell Sensing PCS Brain Radio System
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this study is to use the Activa Primary Cell Sensing PCS device to study Latent Field Potential LFP in the brains of people with Treatment Resistant Depression TRD before and during active stimulation The ultimate goal is to understand the neural network that causes TRD and the changes that DBS cause in that network that results in the antidepressant effects
Detailed Description:
Major depressive disorder is a common disease For many people conventional treatments such as antidepressants are very helpful in relieving the symptoms of this condition But as many as 30 of patients with depression have less than a full response or become resistant to conventional treatments When treatment resistance develops the depression becomes a chronic disease with a very significant burden of morbidity and mortality The reasons that some patients develop Treatment Resistant Depression TRD are not known One current theory for depression is that it results from the dysfunction of a network of regions in the brain and that in treatment resistant patients the network is permanently stuck in the dysfunctional state We have been investigating an experimental treatment for treatment resistant depression TRD based on this network theory known as subcallosal deep brain stimulation SCC DBS This treatment involves placement of electrodes in a specific region of the brain subcallosal cingulate cortex area 25 and then stimulating that area with electricity which resets the regulation of the network resulting in a significant antidepressant response While still experimental our results suggest this may eventually be a useful treatment for some patients with TRD The experiment described in this application is to use a new DBS device that can record the electrical activity in the brain around the site of stimulation The electrical activity is known as Latent Field Potential LFP and is a reflection of the activity if the neural network The new DBS device is an experimental device that has not been approved by the Food and Drug Administration FDA but allows for simultaneous recording of LFP while stimulation is being delivered The device is manufactured by Medtronics and is known as Activa Primary Cell SensingPCS but because it can be used to record the brain electrical activity it is also known as the Brain Radio The Brain Radio is based on an approved device commonly used for DBS for other conditions that has the added sensor capacity The stimulation system is identical to that in the approved device The goal of this investigation is to use the Brain Radio to study LFP in the brains of people with TRD before and during active stimulation The ultimate goal is to understand the neural network that causes TRD and the changes that DBS cause in that network that results in the antidepressant effects We will recruit 10 patients with advanced TRD and implant them with the Brain Radio system The recording system will be to record LFP over 3 years while patients receive stimulation A brief discontinuation study will be conducted after 6 months of stimulation when the device will be turned off and patterns of LFP changes will be recorded All LFP measures will be correlated with the primary clinical response outcome metric the Hamilton Depression Rating Scale The knowledge gained with this experiment will be invaluable to understanding the basic pathology of depression and the antidepressant response This is a unique first in humans test of this device and as such the results are expected to impact our understanding of depression at a fundamental basis
Deep brain stimulation of the subcallosal cingulate white matter SCC25 DBS has been investigated as a new interventional strategy for treatment resistant depression TRD In addition to growing evidence of long-term antidepressant efficacy with chronic stimulation immediate changes in mood attention and psychomotor speed during intra-operative testing have been repeatedly observed These acute electrode contact-specific behavioral effects have successfully guided selection of the optimal contact for chronic DBS The presence of intraoperative behavioral effects is often predictive of long-term outcome It is clear that sustained high frequency stimulation appears to be required to maintain the antidepressant response long-term as discontinuation even after several years of remission is associated with deterioration and return of depression symptoms over several weeks Imaging studies examining effects of chronic SCC25 DBS using positron emission tomography PET demonstrate changes in blood flow and metabolism both in the vicinity of the DBS target and remotely in frontal cortex ventral striatum hypothalamus and amygdalahippocampus These findings combined with more recent diffusion tensor imaging DTI studies provide evidence of the anatomical and functional extent of regional changes mediating antidepressant effects of DBS over time 5-6
Brain changes mediating the observed intra-operative behavioral changes or discontinuation-precipitated relapse are unknown To date none of the studies have been able to address explicit mechanisms of DBS for TRD at the neuronal level during chronic stimulation It is possible to make measurements of neuronal activity with available recording systems only during intraoperative testing Given that TRD requires chronic stimulation to achieve full remission characterization of changes in neural activity throughout the duration of stimulation and development of therapeutic response will be invaluable in further developing and refining this treatment modality Furthermore tracking of neural changes and their behavioral correlates with chronic stimulation and controlled discontinuation would allow characterization of physiologic markers for potential use as feedback signals for further treatment development and optimization
This set of new experiments will build on past experience of utilizing SCC25 DBS in patients with TRD to explore potential neural correlates of antidepressant response This will be done using the ActivaPCS which is a prototype DBS system developed by Medtronic that combines conventional DBS brain electrodes and pulse generator with a sensing device that can chronically read record and download the electrical brain activity known as Local Field Potential LFP at the brain area surrounding the DBS electrode These recordings can be downloaded from the implanted device with an external antenna device similar to the device used to control the pulse generator Given the ability to record LFP locally in the brain and to transmit this information to a receiving station the ActivaPCS device is referred to as the Brain Radio
The ActivaPCS Brain Radio device is an experimental system currently not approved by the FDA This device is based on the ActivaPC system which has FDA approval for use in Parkinsons disease Essential Tremor and has Humanitarian Device Exemption HDE for Dystonia The ActivaPC also has an HDE for use in intractable Obsessive Compulsive Disorder OCD The Brain Radio has sensing technology in addition to the standard stimulation capacity of the approved device that allows for real time recording of LFP in the anatomical location of the electrode both during active stimulation and when stimulation is off As such this is a very powerful research tool that will facilitate investigation of the neuronal changes associated with antidepressant response to chronic DBS This will be the first ever use of this unique cutting edge system in human patients with treatment resistant depression and has the potential to provide unprecedented insight into the fundamental neuronal processes that underlie depressive illness and antidepressant response
Hypothesis 1 Aberrant oscillations in the SCC-prefrontal circuitry are present in TRD patients SCC25 DBS exerts its therapeutic effects by altering these network dynamics Behavioral improvements in TRD patients treated with SCC25 DBS will correlate with discernible LFP changes at specific DBS electrode contacts both acutely and chronically
Hypothesis 2 Stable maintenance of stimulation-induced LFP changes is required for sustained antidepressant response with loss of these changes heralding impending depression relapse
This study will test these hypotheses in 10 TRD patients via recording LFPs with the ActivaPCS system throughout the course of chronic SCC25 DBS Measures of SCC LFP oscillatory activity will be correlated with clinical measures of antidepressant response and with scalp EEG signals
OBJECTIVES Experiment 1 To quantify electrophysiological changes behavioral correlates and EEG changes in the month following implantation when the stimulator is turned OFF
Experiment 1A To characterize the LFP changes for 48 hours post op in response to the brief acute stimulation the patient receives during the implantation procedure Experiment 1B To characterize the changes in LFP patterns in the month after implantation and to establish a baseline before chronic stimulation is initiated The Activa PCS system will be utilized to record LFP during this phase of the protocol
Experiment 2 The stimulator will be turned on 1 month after implantation This experiment will occur on the day of stimulation initiation Clinical data will be recorded and LFP changes will be captured by the Activa PCS system and scalp EEG The stimulator will be cycled through a series of different frequency and current settings while LFPs are recorded
Experiments 3 To quantify LFP changes in response to chronic high frequency SCC25 stimulation and to correlate change patterns with long-term antidepressant response and EEG patterns Stimulation will be initiated one month after implantation and maintained chronically for the subsequent 6 months Clinical assessments LFP and scalp EEG will be routinely recorded during this 6-month period
Experiment 4 To quantify LFP changes when the stimulation is briefly stopped 1 week after 6 months of chronic stimulation Correlation will be made between LFP clinical symptomatic changes and EEG patterns
Experiment 5 To quantify LFP changes over the extended period of exposure to chronic high frequency SCC25 stimulation Clinical response and EEG patterns will be recorded every 6 months and compared to LFP over the battery life of the ActivaPCS system currently estimated at 3 to 5 years after initiation of stimulation
The primary clinical outcome metric is the Hamilton Depression Rating Scale
Deep brain stimulation of the subcallosal cingulate white matter SCC25 DBS has been investigated as a new interventional strategy for treatment resistant depression TRD In addition to growing evidence of long-term antidepressant efficacy with chronic stimulation immediate changes in mood attention and psychomotor speed during intra-operative testing have been repeatedly observed These acute electrode contact-specific behavioral effects have successfully guided selection of the optimal contact for chronic DBS The presence of intraoperative behavioral effects is often predictive of long-term outcome It is clear that sustained high frequency stimulation appears to be required to maintain the antidepressant response long-term as discontinuation even after several years of remission is associated with deterioration and return of depression symptoms over several weeks Imaging studies examining effects of chronic SCC25 DBS using positron emission tomography PET demonstrate changes in blood flow and metabolism both in the vicinity of the DBS target and remotely in frontal cortex ventral striatum hypothalamus and amygdalahippocampus These findings combined with more recent diffusion tensor imaging DTI studies provide evidence of the anatomical and functional extent of regional changes mediating antidepressant effects of DBS over time 5-6
Brain changes mediating the observed intra-operative behavioral changes or discontinuation-precipitated relapse are unknown To date none of the studies have been able to address explicit mechanisms of DBS for TRD at the neuronal level during chronic stimulation It is possible to make measurements of neuronal activity with available recording systems only during intraoperative testing Given that TRD requires chronic stimulation to achieve full remission characterization of changes in neural activity throughout the duration of stimulation and development of therapeutic response will be invaluable in further developing and refining this treatment modality Furthermore tracking of neural changes and their behavioral correlates with chronic stimulation and controlled discontinuation would allow characterization of physiologic markers for potential use as feedback signals for further treatment development and optimization
This set of new experiments will build on past experience of utilizing SCC25 DBS in patients with TRD to explore potential neural correlates of antidepressant response This will be done using the ActivaPCS which is a prototype DBS system developed by Medtronic that combines conventional DBS brain electrodes and pulse generator with a sensing device that can chronically read record and download the electrical brain activity known as Local Field Potential LFP at the brain area surrounding the DBS electrode These recordings can be downloaded from the implanted device with an external antenna device similar to the device used to control the pulse generator Given the ability to record LFP locally in the brain and to transmit this information to a receiving station the ActivaPCS device is referred to as the Brain Radio
The ActivaPCS Brain Radio device is an experimental system currently not approved by the FDA This device is based on the ActivaPC system which has FDA approval for use in Parkinsons disease Essential Tremor and has Humanitarian Device Exemption HDE for Dystonia The ActivaPC also has an HDE for use in intractable Obsessive Compulsive Disorder OCD The Brain Radio has sensing technology in addition to the standard stimulation capacity of the approved device that allows for real time recording of LFP in the anatomical location of the electrode both during active stimulation and when stimulation is off As such this is a very powerful research tool that will facilitate investigation of the neuronal changes associated with antidepressant response to chronic DBS This will be the first ever use of this unique cutting edge system in human patients with treatment resistant depression and has the potential to provide unprecedented insight into the fundamental neuronal processes that underlie depressive illness and antidepressant response
Hypothesis 1 Aberrant oscillations in the SCC-prefrontal circuitry are present in TRD patients SCC25 DBS exerts its therapeutic effects by altering these network dynamics Behavioral improvements in TRD patients treated with SCC25 DBS will correlate with discernible LFP changes at specific DBS electrode contacts both acutely and chronically
Hypothesis 2 Stable maintenance of stimulation-induced LFP changes is required for sustained antidepressant response with loss of these changes heralding impending depression relapse
This study will test these hypotheses in 10 TRD patients via recording LFPs with the ActivaPCS system throughout the course of chronic SCC25 DBS Measures of SCC LFP oscillatory activity will be correlated with clinical measures of antidepressant response and with scalp EEG signals
OBJECTIVES Experiment 1 To quantify electrophysiological changes behavioral correlates and EEG changes in the month following implantation when the stimulator is turned OFF
Experiment 1A To characterize the LFP changes for 48 hours post op in response to the brief acute stimulation the patient receives during the implantation procedure Experiment 1B To characterize the changes in LFP patterns in the month after implantation and to establish a baseline before chronic stimulation is initiated The Activa PCS system will be utilized to record LFP during this phase of the protocol
Experiment 2 The stimulator will be turned on 1 month after implantation This experiment will occur on the day of stimulation initiation Clinical data will be recorded and LFP changes will be captured by the Activa PCS system and scalp EEG The stimulator will be cycled through a series of different frequency and current settings while LFPs are recorded
Experiments 3 To quantify LFP changes in response to chronic high frequency SCC25 stimulation and to correlate change patterns with long-term antidepressant response and EEG patterns Stimulation will be initiated one month after implantation and maintained chronically for the subsequent 6 months Clinical assessments LFP and scalp EEG will be routinely recorded during this 6-month period
Experiment 4 To quantify LFP changes when the stimulation is briefly stopped 1 week after 6 months of chronic stimulation Correlation will be made between LFP clinical symptomatic changes and EEG patterns
Experiment 5 To quantify LFP changes over the extended period of exposure to chronic high frequency SCC25 stimulation Clinical response and EEG patterns will be recorded every 6 months and compared to LFP over the battery life of the ActivaPCS system currently estimated at 3 to 5 years after initiation of stimulation
The primary clinical outcome metric is the Hamilton Depression Rating Scale
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 5UH3NS103550 | NIH | None | httpsreporternihgovquickSearch5UH3NS103550 |