Low-Intensity Focused Ultrasound Pulsation (LIFUP) for the Treatment of Generalized Anxiety Disorder (GAD)

NCT ID: NCT04557891

Last Updated: 2026-02-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-26
• Study Completion Date: 2027-12-31

Brief Summary

There are few treatment options available for patients once they have failed standard psychopharmacological therapy for generalized anxiety disorder. Existing brain stimulation methods such as rTMS fail to target deep brain structures associated with anxiety disorders; structures such as the amygdala. In this double-blind sham-controlled clinical trial, the investigators propose to establish baseline severity of anxiety in 48 patients, then deliver eight treatments over four sessions of focused ultrasound stimulation to the amygdala. Anxiety severity will be assessed using standard psychometric scales after each session, and at follow-ups.

Detailed Description

Anxiety disorders have tremendous disease burden in the United States. Up to 1 in 3 Americans will be diagnosed with an anxiety disorder in their lifetimes. Anxiety treatment is typically consisting of psychotherapy (e.g. cognitive behavioral therapy) and medication management (e.g. benzodiazepines, selective serotonin reuptake inhibitors, etc). With major depressive disorder, rTMS is a suitable alternative treatment for refractory depression, rTMS is not approved for treatment of anxiety, nor can rTMS stimulate deep enough to reach those brain circuits involved in anxiety (e.g. the amygdala). Focused ultrasound is a new treatment modality being developed for several different neuropsychiatric conditions. In this study, the investigators propose to randomize 48 individuals to either active or sham treatment. Each participant will be evaluated to establish a baseline diagnose of generalized anxiety disorder, and then will be reassessed after each treatment session (of which there are four). One week and one month after the last treatment session, the investigators will conduct follow-up evaluations.

Conditions

Generalized Anxiety Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Low Intensity Focused Ultrasound

Device: Low Intensity Focused Ultrasound Device

Low Intensity Focused Ultrasound Pulsation (LIFUP) of amygdala (a key area for anxiety) will be performed during two sessions. The proposed experiment will involve behavioral (e.g. HAM-A) and paramedical (i.e., MRI/fMRI) measurements just before and after each of the two LIFUP sessions (i.e., 5 non-consecutive minutes of stimulation in each session). The device does not produce a sound when operating and as such, the active group will well blinded.

Group Type: EXPERIMENTAL

Active LIFUP Treatment

Intervention Type: DEVICE

8 LIFUP Treatments

Sham

Sham Treatment consists of placing the device but not turning it on. The device does not produce a sound when operating and as such, the sham group will well blinded.

Group Type: SHAM_COMPARATOR

Sham LIFUP Treatment

Intervention Type: DEVICE

8 sham LIFUP treatments

Interventions

Active LIFUP Treatment

8 LIFUP Treatments

Intervention Type: DEVICE

Sham LIFUP Treatment

8 sham LIFUP treatments

Intervention Type: DEVICE

Other Intervention Names

BX Pulsar 1002

Eligibility Criteria

Inclusion Criteria

1. Male or female

2. Age 18-65

3. Normal or corrected-to normal vision and hearing

4. Primary diagnosis of generalized anxiety disorder, moderate/severe per DSM-5. (HAM-A>17) 4a) The duration of the illness must exceed one year.

5. Must be medically stable as determined by investigator

6. Patient must have attempted and failed treatment with at least 2 SSRI and 1 augmentation

7. History of rTMS is permitted, but not required.

Exclusion Criteria

1. Diagnosis of primary DSM-5 anxiety disorder other than GAD 1a) Affective disorders such as unipolar or bipolar depression are permitted as long as GAD is primary

2. Current use of any non-prescribed psychoactive medications or drugs (aside from medications for treatment of GAD)

3. Contraindication to enter the MRI environment

4. Pregnancy (or suspected/possible pregnancy or plan to become pregnant in the short-term)

5. Inability to adhere to treatment schedule

6. Initiation of new anxiolytic treatment at the time of study randomization

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Margaret Distler, MD, PhD

Health Sciences Assistant Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Margaret G Distler, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

University of California, Los Angeles

Los Angeles, California, United States

Site Status: RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Margaret G Distler, MD,PhD

Role: CONTACT

mdistler@mednet.ucla.edu

(310) 794-1553

Andrew Bishay, BS

Role: CONTACT

abishay@mednet.ucla.edu

4243719869

Facility Contacts

Margaret G Distler, MD, PhD

Role: primary

mdistler@mednet.ucla.edu

310-794-1553

Andrew Bishay

Role: backup

abishay@mednet.ucla.edu

Darin Dougherty

Role: primary

ddougherty@mgb.org

617-724-9247

Elisabeth Collins

Role: primary

collieli@musc.edu

843-638-7517

Other Identifiers

CTP-LIFUP-GAD-V1.0

Identifier Type: -

Identifier Source: org_study_id