Investigating LIFUP in Anhedonic Depression

NCT06285474 | Completed

• 1 other identifier: 22-001323
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Anhedonia

Keywords

digital phenotype; ultrasound; depression; anhedonia; imaging

Outcome Measures

Primary Outcomes (4)

• Change in Patient health questionnaire-14 self report measure (PHQ-14) from baseline

  Validated, self-report, 14 item assessment of depressive symptoms in the past 2 weeks. Score range 0- 24. Higher scores indicate higher severity of depressive symptoms.

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

• Change in Positive valence systems scale-21 self report measure (PVSS-21) from baseline

  Validated, self-report 21 item assessment of reward sensitivity. 13 subscales measure different domains of reward sensitivity (range 3-27), with total score (range 1-9) representing overall reward sensitivity. Lower scores indicate more anhedonic responses.

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

• Changes in MRI images from Pre-scan to week 5

  changes in fMRI resting state connectivity, spectroscopy (concentration of glutamate and GABA in the ACC region), and task-based neural activation (using card guessing task) Card Guessing Task: During the scan, participants are asked to guess the value of cards presented on a screen, and are provided immediate feedback as to whether their guesses were correct or not. Participants are informed prior to performing the task, that money is awarded for each correct guess. This task measures reward sensitivity. Apple Gathering Task: Effort is expended by participants squeezing a hand-grip measurement tool, which translates a signal to the screen showing the amount of effort they are expending to receive a pre-determined amount of "reward". Participants can accept or reject trials of effort based on the amount of reward they would be due to receive. This task measures reward sensitivity and motivation.

  Pre-scan, week 5

• Change in Ecological momentary assessment (EMA) from W0/Baseline

  Ecological momentary assessment (EMA) is a custom 16 item self-report assessment of in-the moment mood and activity. This is a data collection instrument without a standardized scoring method.

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

Secondary Outcomes (7)

• Changes in digital behavioral phenotype sleep measurement

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

• Changes in digital behavioral phenotype physical activity measurement

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

• Changes in heart rate

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

• Changes in heart rate variability

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

• Changes in respiratory rate

  Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5

Other Outcomes (20)

• changes in Quick Inventory of Depressive Symptoms (QIDS-SR15) score from W0/Baseline to end of study

  Week 0/Baseline, week 5

• changes in Patient Health Questionnaire (PHQ-9) score from day 2 to week 2

  Day 2, week 1, week 2

• changes in Brief Irritability Test (BITe) score from W0/Baseline to end of study

  Week 0/Baseline, week 5

Study Arms (2)

Active Caudate

EXPERIMENTAL

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.

Device: Low Intensity Focused Ultrasound Pulsation (LIFUP)

Sham Caudate

SHAM COMPARATOR

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.

Device: Low Intensity Focused Ultrasound Pulsation (LIFUP)

Interventions

Low Intensity Focused Ultrasound Pulsation (LIFUP) 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.

Active Caudate; Sham Caudate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Wellcome Trust: collaborator

Study Sites (1)

University of California Los Angeles

Los Angeles, California, 90095-1563, United States

Location

MeSH Terms

Conditions

Depression; Anhedonia

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished Professor

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: February 29, 2024
• Study Start: October 27, 2022
• Primary Completion: April 24, 2024
• Study Completion: April 24, 2024
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data is being made available throughout the course of collection, and will remain available for study for up to 10 years.
• Access Criteria: Researchers permitted access to the deidentified data from this study must be a part of the MC Psych consortium, as designated and approved by the sponsor, Wellcome Trust. All other requests for access to data from this project will be reviewed by the principal investigator for approval.

Locations

US (1)