Trial Outcomes & Findings for Radiosurgical Neuromodulation for Refractory Depression (NCT NCT01403441)

Results Overview

An event that required hospitalization due to an unanticipated worsening of the subjects bipolar disorder.

Recruitment status

TERMINATED

Study phase

NA

Target enrollment

3 participants

Primary outcome timeframe

Baseline and 12 months.

Results posted on

2017-09-05

Participant Flow

Recruitment started in August 2010, through July 2012. Subjects recruited from outpatient referrals. 5 subjects were screened, 3 enrolled.

No group assignment, open label study.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Radiosurgical Neuromodulation for Refractory Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open Treatment Study n=3 Participants Open treatment with Cyberknife System targeting brain area cingulate 25.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	50.3 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 months.

Population: Patients with bipolar disorder in the depressive phase who have not responded to any available treatment

An event that required hospitalization due to an unanticipated worsening of the subjects bipolar disorder.

Outcome measures

Outcome measures
Measure	Radiosurgical Neuromodulation n=3 Participants Bilateral Radiosurgical Neuromodulation using the Cyberknife Radiosurgical Neuromodulation using the Cyberknife: our team has selected 60 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 that correlates with Brodmann area 25 (Cg25).
Serious Adverse Event	1 event

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: Patients with Bipolar disorder in the depressive phase that have not responded to available treatments

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.

Outcome measures

Outcome measures
Measure	Radiosurgical Neuromodulation n=3 Participants Bilateral Radiosurgical Neuromodulation using the Cyberknife Radiosurgical Neuromodulation using the Cyberknife: our team has selected 60 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 that correlates with Brodmann area 25 (Cg25).
Hamilton Depression Rating Scale (HDRS) - 17 Item	24.0 units on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Radiosurgical Neuromodulation n=3 Participants Bilateral Radiosurgical Neuromodulation using the Cyberknife Radiosurgical Neuromodulation using the Cyberknife: our team has selected 60 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 that correlates with Brodmann area 25 (Cg25).
Clinical Global Impression - Severity (CGI-S) at Baseline and 12 Months 12 month	3 units on a scale Standard Deviation 1.2
Clinical Global Impression - Severity (CGI-S) at Baseline and 12 Months Baseline	6 units on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline and 12 months

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

Outcome measures

Outcome measures
Measure	Radiosurgical Neuromodulation n=3 Participants Bilateral Radiosurgical Neuromodulation using the Cyberknife Radiosurgical Neuromodulation using the Cyberknife: our team has selected 60 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 that correlates with Brodmann area 25 (Cg25).
Delis-Kaplan Executive Function System (D-KEFS) Composite Score Baseline	8.4 units on a scale Standard Deviation 2.2
Delis-Kaplan Executive Function System (D-KEFS) Composite Score 12 months	11.8 units on a scale Standard Deviation 2.5

Adverse Events

Radiosurgical Neuromodulation

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Radiosurgical Neuromodulation n=3 participants at risk 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.
Nervous system disorders Psychotic mania	33.3% 1/3 • Number of events 1 • 1 year

Other adverse events

Other adverse events
Measure	Radiosurgical Neuromodulation n=3 participants at risk 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.
Nervous system disorders Signal Abnormality on MRI	33.3% 1/3 • Number of events 1 • 1 year

Additional Information

Dr. Hugh Brent Solvason

Stanford University

Phone: 650 776 4793

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place