Bipolar DisorderNCT01403441
Radiosurgical Neuromodulation for Refractory Depression
A study testing Radiosurgical Neuromodulation using the Cyberknife in people with Bipolar Disorder, run by Stanford University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 22 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Radiosurgical Neuromodulation using the Cyberknife
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Jan 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate, all patients must meet the following criteria:
- Men and women 22-65 years of age
- Primary diagnosis of bipolar depression, as per the Diagnostic and Statistical Manual - Text Revision (DSM IV-TR) criteria
- The current major depressive episode has been for at least one year
- Hamilton Depression Rating Scale (HDRS)-24 item greater than or equal to 20
- Negative urine pregnancy in female subjects
Show all 17Show fewer
- No current psychotic symptoms
- No comorbid post traumatic stress disorder, the inclusion of subjects with other psychiatric comorbidity will be determined by the investigator prior to enrollment
- No personality disorder that in the opinion of the investigator may compromise the subjects ability to participate and be compliant with the elements and procedures of the study
- No substance abuse of dependence in the last 6 months
- A negative urine drug screen
- On a stable dose of their current medication regimen for four weeks
- Treatment resistance: A history of failure to show clinical improvement after at least four different medication trials of adequate duration and dose and one course of ECT. A course of ECT is not mandatory for those who have declined the procedure due to stigma, patient preference, or intolerance. One course of ECT is defined as receiving six acute treatments. (Note: the Antidepressant Treatment History Form (ATHF) does not apply to bipolar depression where mood stabilizers are the treatments of choice in the first three steps in an algorithm to treat bipolar depression)
- No available reasonable treatment options at the time of enrollment
- Competent to understand the risks and potential benefits of the study
- Able to provide written informed consent for the full screening phase, as well as the treatment period of the protocol, including the baseline MRI, CT and positron emission tomography (PET) imaging
- Signed consent form for participation in the study
Who cannot join
- Patients who meet the following criteria will be excluded from participation in this research study:
- Rapid cycling bipolar illness
- History of schizophrenia, schizoaffective disorder, or psychosis
- Severe suicidal thoughts that may put the subject at risk of either an attempted suicide or completed suicide for the duration of the trial, as determined by the investigator at the time of enrollment
- Current substance abuse or in the process of withdrawal from mind-altering substances including alcohol, stimulants, or sedatives
- Undisclosed or undiagnosed unstable medical or neurologic illness including stroke, significant brain malformation, brain mass
Show all 14Show fewer
- Previous whole-brain radiation
- Brain-implanted devices such as deep brain stimulation leads, aneurysm clips
- A history of seizure disorder
- History of moderate to severe brain injury
- Current treatment with either metronidazole or cisplatinum and an inability to discontinue prior to RSN
- Pregnancy or breast feeding
- Unstable medical illness
- Current participation in another investigational trial or participation within 30 days of enrollment
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
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.
Read the detailed description
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.
- Conditions
- Bipolar Disorder
- Being tested
- Radiosurgical Neuromodulation using the Cyberknife
- Keywords
- Refractory Bipolar Depression
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiosurgical Neuromodulation using the CyberknifeDevice
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).
| Study group | Role | What they receive |
|---|---|---|
| Radiosurgical Neuromodulation | Experimental | Bilateral Radiosurgical Neuromodulation using the Cyberknife Receives: Device: Radiosurgical Neuromodulation using the Cyberknife |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious Adverse Event
An event that required hospitalization due to an unanticipated worsening of the subjects bipolar disorder.
Measured: Baseline and 12 months.
Secondary outcomes (3)
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.
Measured: Baseline and 12 months
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).
Measured: 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
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2011 (estimated)
- Study startJul 2010
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: Potential AE
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Precision radiotherapy is delivered on Day 1 using the Cyberknife System to Brodmann area cingulate 25.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hugh Brent Solvason, Stanford University
- Investigators
- Hugh Brent Solvason, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01403441
- Sponsor's protocol ID
- SU-12012010-7249
- Other IDs
- eprotocol 10186
- Status last verified
- Aug 2017
- First submitted
- 25 Jul 2011
- Last updated
- 5 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiosurgical Neuromodulation for Refractory Depression
- ClinicalTrials.gov ID
- NCT01403441
- Acronym / sponsor ID
- SU-12012010-7249
- Conditions
- Bipolar Disorder
- Keywords
- Refractory Bipolar Depression
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Potential AE
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 27 Jul 2011 (estimated)
- Results
- Posted 5 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Precision radiotherapy is delivered on Day 1 using the Cyberknife System to Brodmann area cingulate 25.
| Arm | Type | Receives |
|---|---|---|
| Radiosurgical Neuromodulation | Experimental | Device: Radiosurgical Neuromodulation using the CyberknifeBilateral Radiosurgical Neuromodulation using the Cyberknife |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Men and women 22-65 years of age
- Primary diagnosis of bipolar depression, as per the Diagnostic and Statistical Manual - Text Revision (DSM IV-TR) criteria
- The current major depressive episode has been for at least one year
- Hamilton Depression Rating Scale (HDRS)-24 item greater than or equal to 20
- Negative urine pregnancy in female subjects
Key exclusion criteria (14 listed)
- Patients who meet the following criteria will be excluded from participation in this research study:
- Rapid cycling bipolar illness
- History of schizophrenia, schizoaffective disorder, or psychosis
- Severe suicidal thoughts that may put the subject at risk of either an attempted suicide or completed suicide for the duration of the trial, as determined by the investigator at the time of enrollment
- Current substance abuse or in the process of withdrawal from mind-altering substances including alcohol, stimulants, or sedatives
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Radiosurgical Neuromodulation using the Cyberknifeour 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). | Device | Radiosurgical Neuromodulation |
Primary outcome
Serious Adverse Event
Time frame: Baseline and 12 months.
An event that required hospitalization due to an unanticipated worsening of the subjects bipolar disorder.
3 secondary outcomes
Hamilton Depression Rating Scale (HDRS) - 17 Item
Time frame: Baseline and 12 months
Clinical Global Impression - Severity (CGI-S) at Baseline and 12 Months
Time frame: Baseline and 12 months
Delis-Kaplan Executive Function System (D-KEFS) Composite Score
Time frame: Baseline and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Bipolar Disorder
Enrolling by invitationObservational study
Digital Phenotypes for Predicting Depression_Validation
Major Depressive Disorder, Bipolar I Disorder
Active, not recruiting
Functional Remediation for Older Adults With Bipolar Disorder
Bipolar Disorder
Recruiting
HD-tDCS for Adolescent Bipolar Depression Targeting S1
Adolescent, Bipolar Depression
Not yet recruiting
Anterior Bridge-Preserving Versus Conventional Early Apical Release in Bipolar Enucleation of the Prostate
Benign Prostatic Hyperplasia, Benign Prostatic Obstruction
RecruitingPhase 3
A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
Bipolar Disorder Type I With Mania
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hugh Brent Solvason principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Radiosurgical Neuromodulation using the Cyberknife in people with Bipolar Disorder, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious Adverse Event (time frame: Baseline and 12 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2017.