Deep Brain Stimulation for Refractory PTSD

NCT06705296 | Recruiting Phase 1

• 1 other identifier: 6355
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

PTSD

Keywords

PTSD; DBS; Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (2)

• Number of participants with treatment-related adverse events as assessed by SAFTEE

  The primary objective is to establish the safety of deep brain stimulation in a patient population with treatment refractory PTSD using Systematic Assessment for Treatment Emergent Events

  Every 2 weeks until the 8 weeks mark, every 4 weeks until 6 month mark and every two months until the 2 year mark

• Clinician-Administered PTSD Scale for DSM-5 (CAPS)

  The CAPS assesses PTSD symptoms which have occurred in the past week.

  Every 2 weeks until the 8 weeks mark, every 4 weeks until 6 month mark and every two months until the 2 year mark

Secondary Outcomes (1)

• Hamilton Depression Rating Scale (HAMD)

  Every 2 weeks until the 8 weeks mark, every 4 weeks until 6 month mark and every two months until the 2 year mark

Study Arms (4)

Open label

EXPERIMENTAL

1\) Open label phase (from surgery until postoperative week 24)

Device: Open Label Deep Brain Stimulation

Double-blinded "on/off" phase

PLACEBO COMPARATOR

Double-blinded "on/off" phase (from postoperative week 25 to 33)

Device: Double blinded Deep Brain Stimulation

Prolonged exposure therapy

EXPERIMENTAL

Prolonged exposure therapy (from postoperative week 34to 44)

Behavioral: Prolonged exposure therapy

Closed-loop DBS

EXPERIMENTAL

Closed-loop DBS (from postoperative week 45 to 60).

Device: Closed loop Deep brain stimulation

Interventions

Open Label Deep Brain Stimulation DEVICE

Patients will receive open label deep brain stimulation

Open label

Double blinded Deep Brain Stimulation DEVICE

Patients will receive double blinded deep brain stimulation

Double-blinded "on/off" phase

Prolonged exposure therapy BEHAVIORAL

Patients will receive prolonged exposure therapy

Prolonged exposure therapy

Closed loop Deep brain stimulation DEVICE

Patients will receive closed loop deep brain stimulation

Closed-loop DBS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or Male patients between age 18-70
• Diagnosis of posttraumatic stress disorder as defined by the Diagnostic and Statistical Manual fifth edition (DSM-5).
• Treatment Resistance as defined by the persistence of clinical symptoms despite adequate treatment with four modalities, including a) selective serotonin reuptake inhibitors, b) cognitive behavioral therapy, c) other classes of medications and/or psychotherapy.
• Severe forms of the disease as measured by Clinician Administered PTSD scale (CAPS) scores≥ 50.
• A pattern of chronic stable PTSD lasting at least 1 year.
• Ability to provide informed consent and comply with all testing, follow-ups and study appointments and protocols.

You may not qualify if:

• Any past or current evidence of psychosis or mania (patients with co-morbid depression will not be excluded from the study)
• Active neurologic disease, such as epilepsy
• Alcohol or substance dependence or abuse in the last 6 months, excluding caffeine and nicotine.
• Current suicidal ideation
• Any contraindication to MRI or PET scanning
• Likely to relocate or move out of the country during the study's duration.
• Presence of clinical and/or neurological conditions that may significantly increase the risk of the surgical procedure.
• Currently pregnant (as determined by history and serum HCG) or lactating; for females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Nir Lipsman, MD PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anusha Baskaran, PhD

CONTACT

416-480-6100; anusha.baskaran@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurosurgeon

Model Details: The study will consist of four (4) phases 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 34to 44); 4) Closed-loop DBS (from postoperative week 45 to60).

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: November 26, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)