The Use of Transcranial Focused Ultrasound for the Treatment of Depression and Anxiety

Sponsor

Neurological Associates of West Los Angeles (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04250441

Collaborator

(none)

100

Enrollment

Location

Arm

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this open label study is to evaluate longer term tolerability and early efficacy of transcranial ultrasound in the treatment of patients with refractory depression and anxiety.

Condition or Disease	Intervention/Treatment	Phase
Depression Anxiety	Device: Focused Transcranial Ultrasound	N/A

Detailed Description

The present study is designed as an open label study of patients with refractory depression and anxiety to evaluate longer term tolerability and early efficacy of transcranial ultrasound treatment. Baseline and outcome measures in this study utilize validated tests that are appropriate for repeated measures which are not affected by practice effects. For patients with refractory depression, the target will be the subgenual cingulate (Brodmann's area 25) through a trans temporal scalp window. For patients with anxiety, the target will be the amygdala. Targeting will include reference to scalp fiducials based on the obtained MRI and Doppler waveform confirmation will be obtained because of the ability of TCD to record Doppler signal from the posterior cerebral artery that runs medial to the mesial temporal lobe.

On the day of the ultrasound appointment, patients will undergo ten to thirty minutes of transcranial ultrasound treatment. The sonification device will be aimed at the subgenual cingulate or amygdala, depending on the predetermined condition. Targeting will include reference to scalp fiducials based on the obtained MRI; confirmation of target accuracy will either be obtained by Doppler waveform confirmation or optical tracking technology which co-registers patient neuroimaging with real space. Patients will undergo 8 total sessions of focused ultrasound. Patients will be evaluated at baseline and upon final ultrasound treatment using the same measures obtained upon entry. Safety and any adverse events will be monitored closely.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Use of Transcranial Focused Ultrasound for the Treatment of Depression and Anxiety

Actual Study Start Date :

Nov 1, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment All patients enrolled will receive transcranial focused ultrasound. Target location is dependent on patient condition.	Device: Focused Transcranial Ultrasound The FDA has determined that power intensity limits of 720 mW/cm squared at 2 megaHertz is safe for clinical use; the proposed equipment works within these parameters. Furthermore, monitoring sessions up to one hour as proposed in this study are routinely used in patients even with acute brain injury at 2 megaHertz without any reports of complications induced by the ultrasound device. No brain heating, cavitation or bleeding has been identified with the proposed equipment and protocol. For each individual safety can be followed by performing a selective mental status exam at each session completion.

Arm

Intervention/Treatment

Experimental: Treatment

All patients enrolled will receive transcranial focused ultrasound. Target location is dependent on patient condition.

Device: Focused Transcranial Ultrasound

The FDA has determined that power intensity limits of 720 mW/cm squared at 2 megaHertz is safe for clinical use; the proposed equipment works within these parameters. Furthermore, monitoring sessions up to one hour as proposed in this study are routinely used in patients even with acute brain injury at 2 megaHertz without any reports of complications induced by the ultrasound device. No brain heating, cavitation or bleeding has been identified with the proposed equipment and protocol. For each individual safety can be followed by performing a selective mental status exam at each session completion.

Outcome Measures

Primary Outcome Measures

Beck Depression Inventory [Baseline prior to ultrasound administration]
The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.

Secondary Outcome Measures

Patient Depression Questionnaire [Baseline prior to ultrasound administration]
The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
Patient Depression Questionnaire [After final ultrasound (8 weeks from baseline)]
The PDQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from "0" (not at all), "1" (several days/week), "2" (more than half of the days), and "3" (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful.
Hamilton Depression Rating Scale [Baseline prior to ultrasound administration]
The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of "0" (symptom absent) to "4" (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.
Hamilton Depression Rating Scale [After final ultrasound (8 weeks from baseline)]
The HAM-D is a 17-item, interview style questionnaire. A trained staff member administers this form to a patient and scores the patients' responses on a scale of "0" (symptom absent) to "4" (most severe option per symptom). A higher total score indicates a more severe level of depression. The maximum possible score is 50 points. A change in score of at least 30% is considered clinically meaningful.
Beck Anxiety Inventory [Baseline prior to ultrasound administration]
The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.
Beck Anxiety Inventory [After final ultrasound (8 weeks from baseline)]
The BAI is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety symptoms. Each of the 21 items asks whether the patient has experienced various anxiety symptoms in the last two weeks, and if so, how severely. Each question/answer is scored on a scale value of "0" (not at all) to "3" (severely). Higher total scores indicate more severe anxiety symptoms. The maximum total score possible is 63 points. The standard cutoff scores are: 0-7 = minimal anxiety; 8-15 = mild anxiety; 16-25 = moderate anxiety; 26-63 = severe anxiety. A reduction in score by at least 30% is considered clinically meaningful.
Hamilton Anxiety Rating Scale [Baseline prior to ultrasound administration]
The HAM-A is an observer/rater scale consisting 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.
Hamilton Anxiety Rating Scale [After final ultrasound (8 weeks from baseline)]
The HAM-A is an observer/rater scale consisting 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.
Beck Depression Inventory [After final ultrasound (8 weeks from baseline)]
The BDI-II is a 21-question multiple-choice self-report inventory. Each question involves four possible responses, ranging in intensity from "0" (this item does not apply) to "3" (this item applies severely). The test is scored as the sum of all of the response values; this number is used to determine the severity of depressive symptoms. A score of 0 to 3 is possible for each question with a maximum total score of 63 points. The standard cutoff scores are as follows: 0-13 total points = minimal depression; 14-19 total points = mild depression; 20-28 total points = moderate depression; and 29-63 total points = severe depression. A reduction in the total score by at least 30% is considered to be clinically significant.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 93 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria for Depression:

Diagnosis of Major Depressive Disorder
Score greater than 13 on the Beck Depression Inventory
Failure to remit with 3 antidepressants
At least 18 years of age

Inclusion Criteria for Anxiety:

Diagnosis of Generalized or Acute Anxiety Disorder
Score greater than 22 on the Beck Anxiety Inventory
Failure to remit with 3 anxiolytics
At least 18 years of age

Exclusion Criteria for Depression & Anxiety:

Cognitive decline clearly related to an acute illness
Subjects unable to give informed consent
Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep
Recent surgery or dental work within 3 months of the scheduled procedure.
Pregnancy, women who may become pregnant or are breastfeeding
Advanced terminal illness
Any active cancer or chemotherapy
Any other neoplastic illness or illness characterized by neovascularity
Macular degeneration
Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer)
Advanced kidney, pulmonary, cardiac or liver failure

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurological Associates of West LA	Santa Monica	California	United States	90403

Sponsors and Collaborators

Neurological Associates of West Los Angeles

Investigators

Principal Investigator: Sheldon Jordan, M.D., Neurology Management Associates

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Neurological Associates of West Los Angeles

ClinicalTrials.gov Identifier:

NCT04250441

Other Study ID Numbers:

32222-2

First Posted:

Jan 31, 2020

Last Update Posted:

Sep 9, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Depression

Depressive Disorder

Anxiety Disorders

Study Results

No Results Posted as of Sep 9, 2021