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| ID | Type | Description | Link |
|---|---|---|---|
| eprotocol 10186 |
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Potential AE
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This study is designed to evaluate the safety and effectiveness of an investigational procedure for treating people with treatment resistant bipolar depression (TRD). Precise dose delivery of radiation to the predetermined targets in the brain will be accomplished with known Cyberknife stereotactic radiosurgery methods. This technology is considered to be noninvasive (does not physically invade your body). We will be studying if the Cyberknife influences the sensitivity of certain nerves of your brain. Although many clinical treatments for psychiatric conditions have been done using stereotactic radiosurgery, the present study is experimental, because we are seeking to use more moderate doses of radiation that are intended not to destroy any brain cells, but to normalize or modulate their function.
Main objective: To determine the safety of Radiosurgical Neuromodulation (RSN) for Refractory Depression using X-rays in a population of subjects with severe treatment resistant bipolar depression over a 12-month observational period post treatment. While almost any radiosurgical device could be used, the research team has extensive experience with the Accuray CyberKnife System, K011024, and it will be used for planning and delivery of the 6 megavolt (MV) X-ray treatment for this study.
Participation will be dependent upon subjects having a diagnosis of bipolar depression and meeting criteria for treatment resistance. Treatment resistance will be defined as a failure to show clinical improvement after at least four different medication trials and/or one course of electroconvulsive therapy (ECT) during the current episode. A medication trial is defined as an adequate dose and duration of one of four classes of psychoactive medications: lithium, anticonvulsant mood stabilizers, atypical antipsychotic mood stabilizers, and/or antidepressant medications. One course of ECT is defined as receiving six acute treatments. The study will include subjects who have failed ECT, or have had intolerable side effects to ECT, or elected not to receive such treatment due to stigma, or concern over possible side effects of the ECT treatment itself. The subjects enrolled will have exhausted all reasonable treatment strategies, and currently have no other reasonable or viable treatment options for their illness.
Secondary objective: To examine clinical outcome initially over 3 months, then with follow up at 6, 9 and 12 months. Depression will be assessed using the Hamilton Depression Rating Scale (HDRS) 24 item, while manic symptoms will be measured by using the Young Mania Rating Scale (YMRS), and the Clinical Global Impression of Severity of illness (CGI-S), and Improvement (CGI-I). A battery of neuropsychological tests will be administered as well, assessing memory with the California Verbal Learning Task (CVLT), prefrontal function using a Delas-Kaplan Executive Function System (DKEFS) battery including the DKEFS Sorting task, DKEFS Trails task, DKEFS color-word interference task, and the DKEFS verbal fluency task. In addition, the investigators will request information regarding any possible adverse events that occur during this trial.
The intended use for the CyberKnife System, the radiosurgical device being used in this research study, is to administer radiomodulation to the cingulate cortex target Cg25 in patients with refractory bipolar depression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Radiosurgical Neuromodulation | Experimental | Bilateral Radiosurgical Neuromodulation using the Cyberknife |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Radiosurgical Neuromodulation using the Cyberknife | Device | our team has selected 60 Gray (Gy) as the dose to the target margin to be used for radiosurgical neuromodulation in patients with intractable bipolar disorder; the target being the anterior cingulate (Cg) that correlates with Brodmann area 25 (Cg25). |
| Measure | Description | Time Frame |
|---|---|---|
| Serious Adverse Event | An event that required hospitalization due to an unanticipated worsening of the subjects bipolar disorder. | Baseline and 12 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Hamilton Depression Rating Scale (HDRS) - 17 Item | The HDRS is a rating scale measures the severity of depressive symptoms. The scale consists of 17 symptoms with severity anchors that are scored from 0 to 4. The maximum score (most severe depression) is 68, the lowest (no depressive symptoms) is 0. | Baseline and 12 months |
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Inclusion Criteria:
In order to be eligible to participate, all patients must meet the following criteria:
Exclusion Criteria:
Patients who meet the following criteria will be excluded from participation in this research study:
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| Name | Affiliation | Role |
|---|---|---|
| Hugh Brent Solvason | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University School of Medicine | Stanford | California | 94305 | United States |
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No group assignment, open label study.
Recruitment started in August 2010, through July 2012. Subjects recruited from outpatient referrals. 5 subjects were screened, 3 enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Treatment Study | All three subjects had Cyberknife treatment targeting the subgenual cingulate cortex, and then followed for 12 months observation and assessments of depression severity. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Treatment Resistant Depression
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| ID | Title | Description |
|---|---|---|
| BG000 | Open Treatment Study | Open treatment with Cyberknife System targeting brain area cingulate 25. |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serious Adverse Event | An event that required hospitalization due to an unanticipated worsening of the subjects bipolar disorder. | Patients with bipolar disorder in the depressive phase who have not responded to any available treatment | Posted | Number | event | Baseline and 12 months. |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Radiosurgical Neuromodulation | Precision stereotactic radiotherapy targeted the subgenual cingulate cortex (which approximates Brodmann area cingulate 25) using 60 Gy as the dose to the target margin using the CyberKnife System. Subject 3 had a signal abnormality on the MRI of the brain at 9 month time point which was unchanged 12 months on both T1 and T2 acquisition images. This is one adverse event that was sustained. The presence of the signal abnormality at 9 and 12 months indicates it did not change. A change in this type of signal abnormality would not be expected to resolve on that time scale. This adverse event is one occurrence that sustained for the next 3 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Psychotic mania | Nervous system disorders | Systematic Assessment | The patient self-discontinued Symbyax after 6 months in the study. He had remitted at this point, and felt he did no longer needed this medication, and it was too expensive. He subsequently became hypomanic then manic and required hospitalization. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Signal Abnormality on MRI | Nervous system disorders | Systematic Assessment | Subject 3 had a signal abnormality in the subgenual cingulate cortex on both T1 and T2 images at 9 and 12 months |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Hugh Brent Solvason | Stanford University | 650 776 4793 | solvason@stanford.edu |
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| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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Precision radiotherapy is delivered on Day 1 using the Cyberknife System to Brodmann area cingulate 25.
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| Clinical Global Impression - Severity (CGI-S) at Baseline and 12 Months |
The CGI-S assess the overall severity of depression over the 12 month observation period following Cyberknife System. It is rated from 1 (well or remitted) to 7 (severely ill, among the most depressed). |
| Baseline and 12 months |
| Delis-Kaplan Executive Function System (D-KEFS) Composite Score | D-KEFS is a neurocognitive assessment of executive function. The composite score is derived from scores on tests that include Trails A, Color Word Interference, Verbal Fluency, Sorting, WAIS III Digit Span, and CVLT II Long Delay Free Recall. The scores are reported as deviation from a mean of 10, with a standard deviation of 3. A score of 7 is one standard deviation below the mean, while a score of 13 is 1 standard deviation above the mean. Higher numeric outcomes reflect better performance on the test, lower values reflect poorer performance. Results reflect scores at baseline, and 12 month observation period following Cyberknife System | Baseline and 12 months |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Secondary | Hamilton Depression Rating Scale (HDRS) - 17 Item | The HDRS is a rating scale measures the severity of depressive symptoms. The scale consists of 17 symptoms with severity anchors that are scored from 0 to 4. The maximum score (most severe depression) is 68, the lowest (no depressive symptoms) is 0. | Patients with Bipolar disorder in the depressive phase that have not responded to available treatments | Posted | Mean | Standard Deviation | units on a scale | Baseline and 12 months |
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| Secondary | Clinical Global Impression - Severity (CGI-S) at Baseline and 12 Months | The CGI-S assess the overall severity of depression over the 12 month observation period following Cyberknife System. It is rated from 1 (well or remitted) to 7 (severely ill, among the most depressed). | Posted | Mean | Standard Deviation | units on a scale | Baseline and 12 months |
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| Secondary | Delis-Kaplan Executive Function System (D-KEFS) Composite Score | D-KEFS is a neurocognitive assessment of executive function. The composite score is derived from scores on tests that include Trails A, Color Word Interference, Verbal Fluency, Sorting, WAIS III Digit Span, and CVLT II Long Delay Free Recall. The scores are reported as deviation from a mean of 10, with a standard deviation of 3. A score of 7 is one standard deviation below the mean, while a score of 13 is 1 standard deviation above the mean. Higher numeric outcomes reflect better performance on the test, lower values reflect poorer performance. Results reflect scores at baseline, and 12 month observation period following Cyberknife System | Posted | Mean | Standard Deviation | units on a scale | Baseline and 12 months |
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