Deep Brain Stimulation for Treatment Refractory PTSD

Study Overview
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Brief Summary
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This is a phase I, non-blinded, non-randomized, pilot trial for safety and efficacy of deep brain stimulation for PTSD. A substantial number of individuals continue to experience PTSD symptoms despite appropriate medical treatment. In psychotherapy-based studies, over 30% of patients that completed a full course of treatment continue to meet criteria for PTSD. Response rates to treatment with SSRIs are usually no higher than 60%. This study would be the first exploration of a surgical therapy for refractory PTSD. The subgenual cingulate plays a role in mechanisms of this disorders and has been successfully targeted with DBS for the treatment of depression. 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.

Official Title
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Deep Brain Stimulation (DBS) for the Treatment of Refractory Post-Traumatic Stress Disorder (PTSD): Pilot Trial

Conditions
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Post-Traumatic Stress Disorder

Intervention / Treatment
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* Device: Deep Brain Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or Male patients between age 18-70 Diagnosis of posttraumatic stress disorder as defined by the Diagnostic and Statistical Manual fifth edition (DSM V). 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 Exclusion Criteria: 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 one year 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep Brain Stimulation<br> | Device: Deep Brain Stimulation<br>* DBS offers the opportunity to insert electrodes into deep brain structures and electrically stimulate them in a titratable and ultimately reversible manner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events using SAFTEE collateral effects scale. | Adverse events (AE) will be recorded and categorized according to severity and relationship to procedure. All AEs will be assessed for their relationship to the study procedure. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale (HAMD) | The HAMD is designed to rate the severity of depression in patients. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥ 23 = Very Severe Depression | 1 year | 
| Beck's Depression Inventory (BDI) | BDI is a self-rated depression scale. 1-10:These ups and downs are considered normal;11-16: Mild mood disturbance; 17-20: Borderline clinical depression; 21-30: Moderate depression; 31-40: Severe depression; over 40: Extreme depression | 1 year | 
| Beck's Anxiety Inventory (BAI) | BAI is a self-rated anxiety scale. Score of 0 - 21 = low anxiety Score of 22 - 35 = moderate anxiety Score of 36 and above = potentially concerning levels of anxiety | 1 year | 
| Clinician-Administered PTSD Scale (CAPS) | The CAPS is a semi-structured interview that is designed to assess the essential features of Posttraumatic Stress Disorder. | 1 year | 
| Davidson Trauma Scale (DTS) | Self-report measure that assesses PTSD. The DTS yields a frequency score (ranging from 0 to 68), severity score (ranging from 0 to 68), and total score (ranging from 0 to 136). It can be used to make a preliminary determination about whether the symptoms meet DSM criteria for PTSD. Scores can also be calculated for each of the 3 PTSD symptom clusters (i.e., B, C, and D). | 1 year | 
| Short PTSD Rating Interview (SPRINT) | self-report measure that assesses the core symptoms of PTSD (intrusion, avoidance, numbing, arousal), somatic malaise, stress vulnerability, and role and social functional impairment. Symptoms are rates on five point scales from 0 (not at all) to 4 (very much). | 1 year | 
| Clinical Global Impression (CGI) | CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score. | 1 year | 
| Global Functioning Assessment (GFA) | GAF assigns a clinical judgment in numerical fashion to the individual's overall functioning level. Impairments in psychological, social and occupational/school functioning are considered, but those related to physical or environmental limitations are not. The scale ranges from 0 (inadequate information) to 100 (superior functioning). | 1 year | 
| 36-Item Short Form Health Survey (SF-36) | SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting. | 1 year | 
| The State-Trait Anxiety Inventory (STAI) | STAI is a commonly used measure of trait and state anxiety. It can be used in clinical settings to diagnose anxiety and to distinguish it from depressive syndrome. All items are rated on a 4-point scale (e.g., from Almost Never to Almost Always). Higher scores indicate greater anxiety. | 1 year | 
| Hamilton Anxiety Rating Scale (HAMA) | The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | 1 year | 
| Sheehan disability scale (SDS) | The SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. Total score 0-30 (0 unimpaired, 30 highly impaired) Work/school (0-10) Social life (0-10) Family life/home responsibilities (0-10 Scores of ≥5 on any of the 3 scales; high scores are associated with significant functional impairment. | 1 year | 
| Positive and negative affect (PANAS) | PANAS comprises two mood scales, one that measures positive affect and the other which measures negative affect. Used as a psychometric scale, the PANAS can show relations between positive and negative affect with personality stats and traits. Ten descriptors are used for each PA scale and NA to define their meanings. Participants in the PANAS are required to respond to a 20-item test using 5-point scale that ranges from very slightly or not at all (1) to extremely (5). | 1 year |