Investigating LIFUP in Anhedonic Depression

NCT ID: NCT06285474

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-27
• Study Completion Date: 2024-04-24

Brief Summary

This study will observe changes in brain imaging, behavior, and symptom measures following intervention with low intensity focused ultrasound pulsation (LIFUP) targeting reward circuitry in individuals who are depressed and anhedonic.

Detailed Description

Participants will wear a provided Apple watch and download a study app to their personal phones in order for activity and phone use metrics to be collected. Participants will respond to weekly email surveys, daily ecological momentary assessment (EMA) surveys, complete computer-based neurocognitive assessments, undergo a baseline MRI scan with spectroscopy, receive 3 sessions of LIFUP sonication, undergo a follow up MRI with spectroscopy, then continue to be followed with surveys, neurocognitive assessment, and watch/phone data collection for 3 weeks after follow up MRI scan.

Participants will be randomized 1:1 active:sham to receive LIFUP targeting the caudate head of the brain. Conditions will be double blinded so that neither participants nor investigators or research staff know if active or sham sonication is being administered.

Conditions

Depression; Anhedonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Active Caudate

Low Intensity Focused Ultrasound Pulsation (LIFUP) will be directed at the caudate head. To minimize the ultrasound energy's exposure to air, a gel pad will be placed between the transducer and the participant's scalp. The sonication protocol will consist of 10 ultrasound sonications in a 30 s ON, 30 s OFF fashion at 650KHz, Ispta≤720 mW/cm2, 50% duty cycle, 5ms pulse width, 1.44W/cm2 ISPPA, and 100Hz pulse repetition frequency." For active sonication, the gel pad will allow the ultrasound energy to pass through. The sham/active gel pads are identical in appearance.

Group Type: EXPERIMENTAL

Low Intensity Focused Ultrasound Pulsation (LIFUP)

Intervention Type: DEVICE

All participants will undergo 3 identical LIFUP sessions. All sessions must occur at least 1 day apart, and no more than 3 days apart, such that sessions may occur at minimum on days 1, 3, 5 and at maximum may occur on days 1, 5, 9.

Sham Caudate

Low Intensity Focused Ultrasound Pulsation (LIFUP) will be directed at the caudate head. To minimize the ultrasound energy's exposure to air, a gel pad will be placed between the transducer and the participant's scalp. The sonication protocol will consist of 10 ultrasound sonications in a 30 s ON, 30 s OFF fashion at 650KHz, Ispta≤720 mW/cm2, 50% duty cycle, 5ms pulse width, 1.44W/cm2 ISPPA, and 100Hz pulse repetition frequency." For sham sonication, the gel pad will block close to all of the ultrasound energy from the transducer from entering the brain. The sham/active gel pads are identical in appearance.

Group Type: SHAM_COMPARATOR

Low Intensity Focused Ultrasound Pulsation (LIFUP)

Intervention Type: DEVICE

All participants will undergo 3 identical LIFUP sessions. All sessions must occur at least 1 day apart, and no more than 3 days apart, such that sessions may occur at minimum on days 1, 3, 5 and at maximum may occur on days 1, 5, 9.

Interventions

Low Intensity Focused Ultrasound Pulsation (LIFUP)

All participants will undergo 3 identical LIFUP sessions. All sessions must occur at least 1 day apart, and no more than 3 days apart, such that sessions may occur at minimum on days 1, 3, 5 and at maximum may occur on days 1, 5, 9.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• • Between the ages of 18 and 65

• Fluent in English
• Own functioning iOS smart phone (iPhone 8 or later, iOS 15 or newer) with access to reliable data plan and Wi-Fi
• Right-handed
• Normal or corrected to normal vision
• Willingness to participate in the study, including wearing the provided Apple Watch, respond to remote survey prompts, complete an MRI scan, and provide a recorded interview.
• Able to read and understand a written informed consent form
• Reside in the Los Angeles area for the duration of the study
• If enrolled in IRB#22-000059, have completed the majority of assessments.
• Eligible for MRI scanning and neuromodulation
• Willing to receive LIFUP, participate in another MRI scan, keep a study app on their personal phone, and complete 5-7 weeks of assessments.
• PVSS <6.5 at screening

• If screened from the general population, PVSS severity must be endorsed in self-report as having lasted for a period of at least 3 months.
• If screened from IRB#22-000059 scores must average <6.5 at week 6, and stable through study exit. "Stable" defined as the average of all PVSS scores from week 6 through study exit is <6.5
• PHQ scores > 10 at screening

• If screened from the general population, PHQ severity must be endorsed in self-report as having lasted for a period of at least 3 months.
• If screened from IRB#22-000059 scores must average >/= 10 at week 6, and stable through study exit. "Stable" defined as the average of all PHQ scores from week 6 through study exit is >/=10

Exclusion Criteria

• Current tobacco smoker of >11 cigarettes/day or the nicotine equivalent
• Current report of alcohol or substance abuse or dependence
• Recent changes in antidepressant dosing or medication (dose and medication need to be stabilized within the last 2 weeks)
• Any diagnosis of major neurological condition impairing mobility, cognition, or language ability including multiple sclerosis, Parkinson's disease or other movement disorder, motor neuron disease, stroke, dementia
• Any other diagnosis involving chronic mobility impairment including spinal cord injuries, or severe osteoarthritis of knee or hip
• Reported diagnosis of schizophrenia or psychotic symptoms
• Participants currently taking benzodiazepines must agree to refrain from taking this medication for 12 hours before their scan, as well as refrain from any allergy or cold medication (diphenhydramine) that causes sleepiness (e.g. Benadryl).
• History of brain tumor or brain surgery
• History of stroke or seizure
• Contraindications for MRI scanning, including pregnancy, metal implants, braces, significant grip impairment and claustrophobia
• Unable to complete 3 LIFUP sessions within 1 month of completing the MRI scan for IRB#22-000059
• Unable to complete an MRI scan
• Currently taking benzodiazepines, or taken benzodiazepines in the past 8 weeks
• Any previous treatment with electroconvulsive therapy (ECT) or deep brain stimulation (DBS) due to increased risk of seizure and unclear evidence of how LIFUP will affect individuals who have received these treatments.
• Less than 6 months since any other neuromodulation treatment such as transcranial magnetic stimulation (TMS), Vagal nerve electrostimulation, or transcranial direct current stimulation(TDCS).
• Less than 6 months since prescribed ketamine infusion or other intensive, acute therapy for depressive symptoms.
• History of medical event(s) likely to result in neurological abnormalities including diagnoses of Alzheimer's, Parkinson's, neurodegenerative disorders, movement disorders, or reports of seizures or history of brain tumors.
• Unwilling or unable to refrain from making significant changes to hair style after enrollment and before LIFUP sessions are complete. (ie. full hair style to shaved head, significant change in locs, etc)

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

Sponsors

Wellcome Trust

OTHER

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Michelle Craske

Distinguished Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of California Los Angeles

Los Angeles, California, United States

Countries

United States

Other Identifiers

22-001323

Identifier Type: -

Identifier Source: org_study_id