NCT06705296

Deep Brain Stimulation for Refractory PTSD

Deep Brain Stimulation (DBS) for the Treatment of Refractory Post-Traumatic Stress Disorder (PTSD)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Sunnybrook Health Sciences Centre · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Treatment refractory PTSD is a chronic and debilitating psychiatric disorder associated with high morbidity. Despite advances in neuroimaging, genetics, pharmacology and psychosocial interventions in the last half century, little progress has been made in altering the natural history of the condition or its outcome. This study would be the first exploration of a surgical therapy for refractory PTSD. The subgenual cingulate plays a role in mechanisms of this disorder and has been successfully targeted with DBS for the treatment of depression The study will proceed in three stages: pre-operative, operative and post-operative. In the pre-operative stage, consent will be obtained and patients will be scheduled for additional investigations, including neuroimaging (MRI), neuropsychological testing, psychophysiological testing, and a pre-operative assessment by the anesthesia service. In the operative stage, patient will have a stereotactic frame attached directly to their skull. The patient will then undergo a computed tomography (CT) scan with the frame in place, followed by transport directly to the operating room. A skin incision will be made and two burr holes drilled through the skull. After target identification DBS electrodes will be inserted and fixed in place. Patients will be then immediately anesthetized (general anesthesia) for the next step of the surgery. This will involve implanting an internal pulse generator (IPG) under the collarbone and connecting it to the DBS electrodes. During the post-operative phase, patients will return to the clinic 2 weeks after surgery.DBS programming visits will happen biweekly for three months, and monthly thereafter.

Detailed description

Treatment refractory PTSD is a chronic and debilitating psychiatric disorder associated with high morbidity. Despite advances in neuroimaging, genetics, pharmacology and psychosocial interventions in the last half century, little progress has been made in altering the natural history of the condition or its outcome. It has further become increasingly accepted that this condition results, at least in part, from dysfunctional neuroanatomic circuits, whose activity and deviations can be detected with sophisticated neuroimaging techniques. Much progress has also been made in mapping the psychology of the illness to underlying neuroanatomic and neurophysiologic processes that drive and maintain these behaviours. This study would be the first exploration of a surgical therapy for refractory PTSD. The subgenual cingulate plays a role in mechanisms of this disorder and has been successfully targeted with DBS for the treatment of depression (a highly incident co-morbidity in patients with treatment refractory PTSD). There are currently no brain based, targeted therapies for treatment refractory PTSD with or without co-morbid depression (only the few patients described above). This study will be the first powered clinical trial exploring deep brain stimulation in this patient population. This is a phase I, non-randomized, pilot trial for safety and efficacy of deep brain stimulation for PTSD. Patients who meet inclusion and exclusion criteria will be identified and recruited from the practices of Sunnybrook psychiatrists. The study will proceed in three stages: pre-operative, operative and post-operative. In the pre-operative stage, consent will be obtained and patients will be scheduled for additional investigations, including neuroimaging (MRI), neuropsychological testing, psychophysiological testing, and a pre-operative assessment by the anesthesia service. A clinical interview will be used to understand experiences of patients and a family member of each patient (i.e. parent, significant other, spouse, partner, informant, etc.). In the operative stage, patient will have a stereotactic frame attached directly to their skull. The patient will then undergo a computed tomography (CT) scan with the frame in place, followed by transport directly to the operating room. A skin incision will be made and two burr holes drilled through the skull. After target identification DBS electrodes will be inserted and fixed in place. Patients will be then immediately anesthetized (general anesthesia) for the next step of the surgery. This will involve implanting an internal pulse generator (IPG) under the collarbone and connecting it to the DBS electrodes . Once surgery is over, the patient will be woken up, extubated, and transferred to the recovery room. From there, patients will go to the to the neurosurgical ward (D5). During the post-operative phase, patients will return to the clinic 2 weeks after surgery.DBS programming visits will happen biweekly for three months, and monthly thereafter. Twenty (20) subjects will be enrolled and study duration for each patient will be of 60 weeks. The study will consist of four (4) phases to be detailed below: 1) Open label phase (from surgery until postoperative week 24); 2) Double-blinded "on/off" phase (from postoperative week 25 to 33); 3) Prolonged exposure therapy (from postoperative week 34 to 44); 4) Closed-loop DBS (from postoperative week 45 to 60). We believe that the scientific significance lay above all, in the development of a novel treatment alternative in the significant portion of this patient population who fail to respond to currently available treatments. The development of a therapy that targets brain structures known to play a role in this disease would be a substantial step forward in the treatment and understanding of these conditions.

Conditions

• PTSD

Interventions

Type	Name	Description
DEVICE	Open Label Deep Brain Stimulation	Patients will receive open label deep brain stimulation
DEVICE	Double blinded Deep Brain Stimulation	Patients will receive double blinded deep brain stimulation
BEHAVIORAL	Prolonged exposure therapy	Patients will receive prolonged exposure therapy
DEVICE	Closed loop Deep brain stimulation	Patients will receive closed loop deep brain stimulation

Timeline

• Start date: 2024-11-01
• Primary completion: 2026-11-01
• Completion: 2026-11-01
• First posted: 2024-11-26
• Last updated: 2024-11-26

Locations

1 site across 1 country: Canada