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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04250441
• Other study ID #: 32222-2
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 1, 2018
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: Neurological Associates of West Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 93 Years

Eligibility

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 15 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

Related Conditions & MeSH terms

• Anxiety
• Anxiety Disorders
• Depression
• Depressive Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	Neurological Associates of West LA	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Neurological Associates of West Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (33)

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McDannold N, Vykhodtseva N, Hynynen K. Blood-brain barrier disruption induced by focused ultrasound and circulating preformed microbubbles appears to be characterized by the mechanical index. Ultrasound Med Biol. 2008 May;34(5):834-40. doi: 10.1016/j.ultrasmedbio.2007.10.016. Epub 2008 Jan 22. — View Citation

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* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beck Depression Inventory	[Primary for patients enrolled for depression] 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.	Baseline prior to ultrasound administration (
Primary	Hamilton Anxiety Rating Scale	[Primary for patients enrolled for anxiety] 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.	Baseline prior to ultrasound administration
Secondary	Hamilton Anxiety Rating Scale	[Administered to patients enrolled with anxiety] 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.	After final ultrasound (8 weeks from baseline)
Secondary	Beck Anxiety Inventory	[Administered to patients enrolled with anxiety] 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.	Baseline prior to ultrasound administration
Secondary	Beck Anxiety Inventory	[Administered to patients enrolled with anxiety] 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.	After final ultrasound (8 weeks from baseline)
Secondary	Patient Depression Questionnaire	[Administered to patients enrolled with depression] 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.	After final ultrasound (8 weeks from baseline)
Secondary	Hamilton Depression Rating Scale	[Administered to patients enrolled with depression] 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.	Baseline prior to ultrasound administration
Secondary	Hamilton Depression Rating Scale	[Administered to patients enrolled with depression] 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.	After final ultrasound (8 weeks from baseline)
Secondary	Beck Depression Inventory	[Administered to patients enrolled with depression] 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.	After final ultrasound (8 weeks from baseline)