Deep Brain Stimulation for Treatment Refractory PTSD
Primary Purpose
Post-Traumatic Stress Disorder
Status
Unknown status
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Deep Brain Stimulation
Sponsored by
About this trial
This is an interventional treatment trial for Post-Traumatic Stress Disorder
Eligibility Criteria
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
Sites / Locations
- Sunnybrook Health Sciences Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Deep Brain Stimulation
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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
Clinician-Administered PTSD Scale (CAPS)
The CAPS is a semi-structured interview that is designed to assess the essential features of Posttraumatic Stress Disorder.
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).
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).
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.
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).
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.
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.
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.
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.
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).
Full Information
NCT ID
NCT03416894
First Posted
January 8, 2018
Last Updated
March 15, 2021
Sponsor
Sunnybrook Health Sciences Centre
1. Study Identification
Unique Protocol Identification Number
NCT03416894
Brief Title
Deep Brain Stimulation for Treatment Refractory PTSD
Official Title
Deep Brain Stimulation (DBS) for the Treatment of Refractory Post-Traumatic Stress Disorder (PTSD): Pilot Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 19, 2018 (Actual)
Primary Completion Date
November 10, 2021 (Anticipated)
Study Completion Date
November 10, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sunnybrook Health Sciences Centre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-Traumatic Stress Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Deep Brain Stimulation
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
Deep Brain Stimulation
Intervention Description
DBS offers the opportunity to insert electrodes into deep brain structures and electrically stimulate them in a titratable and ultimately reversible manner
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events using SAFTEE collateral effects scale.
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Hamilton Depression Rating Scale (HAMD)
Description
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
Time Frame
1 year
Title
Beck's Depression Inventory (BDI)
Description
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
Time Frame
1 year
Title
Beck's Anxiety Inventory (BAI)
Description
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
Time Frame
1 year
Title
Clinician-Administered PTSD Scale (CAPS)
Description
The CAPS is a semi-structured interview that is designed to assess the essential features of Posttraumatic Stress Disorder.
Time Frame
1 year
Title
Davidson Trauma Scale (DTS)
Description
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).
Time Frame
1 year
Title
Short PTSD Rating Interview (SPRINT)
Description
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).
Time Frame
1 year
Title
Clinical Global Impression (CGI)
Description
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.
Time Frame
1 year
Title
Global Functioning Assessment (GFA)
Description
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).
Time Frame
1 year
Title
36-Item Short Form Health Survey (SF-36)
Description
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting.
Time Frame
1 year
Title
The State-Trait Anxiety Inventory (STAI)
Description
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.
Time Frame
1 year
Title
Hamilton Anxiety Rating Scale (HAMA)
Description
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.
Time Frame
1 year
Title
Sheehan disability scale (SDS)
Description
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.
Time Frame
1 year
Title
Positive and negative affect (PANAS)
Description
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).
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Deep Brain Stimulation for Treatment Refractory PTSD
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