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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Generalized Anxiety Disorder
• Intervention / Treatment: Device: Active LIFUP Treatment; Device: Sham LIFUP Treatment

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margaret G Distler, MD,PhD; Phone Number: (310) 794-1553; Email: mdistler@mednet.ucla.edu
• Study Contact Backup: Name: Andrew Swenson, BS; Phone Number: (310) 206-5133; Email: aswenson@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California, Los Angeles
      • Principal Investigator: Taylor P Kuhn, PhD
      • Contact: Margaret G Distler, MD, PhD; Phone Number: 310-794-1553; Email: mdistler@mednet.ucla.edu
      • Contact: Andrew Swenson; Phone Number: 3102065133; Email: aswenson@mednet.ucla.edu
      • Principal Investigator: Margaret G Distler, MD,PhD
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Recruiting
      • Massachusetts General Hospital
      • Sub-Investigator: Tina Chou, PhD
      • Principal Investigator: Darin D Dougherty, MD
      • Contact: Tina Chou, PhD; Email: tchou@mgh.harvard.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Mark S George, MD
      • Contact: Bridgette Holland; Phone Number: 843-638-7517; Email: hollanbr@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Device: Active LIFUP Treatment; 8 LIFUP Treatments; Other Names: BX Pulsar 1002
Sham Comparator: 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.	Device: Sham LIFUP Treatment; 8 sham LIFUP treatments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Anxiety Rating Scale (HAM-A)	HAM-A is a rating scale for measuring the severity of anxiety symptoms.	1 week after the fourth LIFUP treatment

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Medical University of South Carolina; Massachusetts General Hospital
• Investigators: Principal Investigator: Margaret G Distler, MD,PhD, University of California, Los Angeles; Principal Investigator: Taylor P Kuhn, PhD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 15, 2020
• First Posted (Actual): September 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: focused ultrasound
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: CTP-LIFUP-GAD-V1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No