Investigating LIFUP in Anhedonic Depression

Depression Clinical Trial

— ILIAD  

Official title:

Investigating Low Intensity Focused Ultrasound Pulsation (LIFUP) in Anhedonic Depression

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06285474
• Other study ID #: 22-001323
• Status: Enrolling by invitation
• Phase: N/A
• Start date: October 27, 2022
• Est. completion date: April 30, 2024

Study information

• Verified date: February 2024
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 46
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Anhedonia
• Depression
• Depressive Disorder

Intervention

Device:
• 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.

Locations

Country	Name	City	State
United States	University of California Los Angeles	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	Wellcome Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	changes in Quick Inventory of Depressive Symptoms (QIDS-SR15) score from W0/Baseline to end of study	Validated, 15 item self-report of depressive symptoms. Total score range is 0-24 with higher total scores indicating more severe depressive symptoms.	Week 0/Baseline, week 5
Other	changes in Patient Health Questionnaire (PHQ-9) score from day 2 to week 2	Validated, self-report 9 item assessment of depressive symptoms including suicidal ideation. Score range 0-27. Higher scores indicate higher severity of depressive symptoms.	Day 2, week 1, week 2
Other	changes in Brief Irritability Test (BITe) score from W0/Baseline to end of study	Validated, 5 item self-report irritability measure. Score range 5-30 with higher scores indicating more irritable responses.	Week 0/Baseline, week 5
Other	changes in Generalized Anxiety Disorder (GAD-7) score from W0/Baseline to end of study	Validated, 7 item self-report of anxiety symptoms. Score range 0-21 with higher scores indicating more anxious symptoms.	Week 0/Baseline, week 5
Other	Changes in Snaith Hamilton Pleasure Scale (SHAPS) score from W0/Baseline to end of study	Validated, 14 item self-report measure of hedonic experience or positive valence. Total score range is 0-14 with higher scores representing more anhedonic responses.	Week 0/Baseline, week 5
Other	Changes in Suicidal Ideation measure from Pre-scan to end of study	Custom, 22 item self-report measure of history and current presence of suicidal ideation and behavior. Domain scores assess current and lifetime severity. Score range 0-1 with higher scores indicating more severe suicidal ideation and risk.	Pre-scan, week 5
Other	changes in Apathy Motivation Index (AMI) score from W0/Baseline to end of study	Validated, 18 item self-report index of apathy and motivation. Domain scores assess behavioral, social, and emotional responses. Score range for each domain is 0-4 with higher scores indicating more apathetic or unmotivated responses.	Week 0/Baseline, week 5
Other	changes in Eudaimonic Well-Being Questionnaire (EWBQ) score from W0/Baseline to end of study	Custom, 5 item survey assessing self-reported well-being focused on values, meaning and purpose in life. Total score range 0-20 with lower scores reflecting responses of low wellbeing.	Week 0/Baseline, week 5
Other	Changes in Work and Social Adjustment Scale (WSAS) score from W0/Baseline to end of study	Validated, 8 item assessment of self-reported functional impairment of current symptoms in work/school, social life, and family life. Total score range 0-40 with higher scores indicating more impairment.	Week 0/Baseline, week 5
Other	Changes in Ruminative Response Scale (RRS) - brooding subscale score from W0/Baseline to end of study	Validated, 9 item assessment of self-reported symptoms of rumination. Total score range 0-27 with higher scores reflecting more rumination.	Week 0/Baseline, week 5
Other	changes in Trauma History Questionnaire (THQ) score from W0/Baseline to end of study	Validated self-report measure of traumatic life events. This is a data collection instrument without a standardized scoring method which will be used as a covariate.	Week 0/Baseline, week 5
Other	changes in Routines Survey from W0/Baseline to end of study	Custom self-report of daily activities and phone usage. This is a data collection instrument without a scoring method.	Week 0/Baseline, week 5
Other	changes in USDA Housing and Food Insecurity score from W0/Baseline to end of study	Validated, 6 item assessment of self-reported household food security. Total score range 0-6 with higher scores indicating higher food insecurity. This measure will be used as a covariate.	Week 0/Baseline, week 5
Other	changes in Holmes-Rahe Life Stress Survey score from W0/Baseline to end of study	Validated, 40 item assessment of self-reported exposure to moderate-to-major stressful life events. Score range 0-40 with higher scores representing more exposure to stressful life events. This measure will be used as a covariate.	Week 0/Baseline, week 5
Other	Changes in emotion recognition accuracy scores from Pre-scan to end of study	TestMyBrain is a computer administered neurocognitive battery that will provide scores for emotion recognition accuracy. Where accuracy scores represent the proportion correct responses across trials, with higher scores indicating more accurate responses.	Pre-scan, week 5
Other	Changes in emotion recognition response times from Pre-scan to end of study	TestMyBrain is a computer administered neurocognitive battery that will provide scores for scores for emotion recognition response times. Higher response times indicate taking longer to generate a response.	Pre-scan, week 5
Other	Changes in continuous concentration accuracy scores from Pre-scan to end of study	TestMyBrain is a computer administered neurocognitive battery that will provide scores for continuous concentration accuracy. Where accuracy scores represent the proportion correct responses across the trial, with higher scores indicating more accurate responses.	Pre-scan, week 5
Other	Changes in continuous concentration response times from Pre-scan to end of study	TestMyBrain is a computer administered neurocognitive battery that will provide scores for scores for continuous concentration response times. Higher response times indicate taking longer to generate a response.	Pre-scan, week 5
Other	Changes in continuous concentration error scores from Pre-scan to end of study	TestMyBrain is a computer administered neurocognitive battery that will provide scores for continuous concentration errors. Error scores represent the proportion errors committed during the trial, with higher scores indicating more errors.	Pre-scan, week 5
Other	Changes in Apple Gathering task behavior from Pre-scan to end of study	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
Primary	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
Primary	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
Primary	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
Primary	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	Changes in digital behavioral phenotype sleep measurement	Apple watch & phone sensor metrics of sleep.	Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5
Secondary	Changes in digital behavioral phenotype physical activity measurement	Apple watch & phone sensor metrics of physical activity.	Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5
Secondary	Changes in heart rate	Apple watch & phone sensor metrics of heart rate.	Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5
Secondary	Changes in heart rate variability	Apple watch & phone sensor metrics of heart rate variability.	Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5
Secondary	Changes in respiratory rate	Apple watch & phone sensor metrics of respiratory rate.	Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5
Secondary	changes in World Health Organization (WHO) -5 Wellbeing index score from W0/Baseline to end of study	Validated, 5 item assessment of self-reported current mental wellbeing. Total score range 0-25, is multiplied by 4 to give the final score, with 0 representing the worst imaginable well-being and 100 representing the best imaginable well-being.	Week 0/Baseline, week 5
Secondary	changes in Pittsburgh Sleep Quality Index (PSQI) score from W0/Baseline to end of study	Validated, 18 item self-report of recent sleep quality. Domain scores calculate items like sleep latency, disturbance, etc. and are used to calculate total score. Total score range is 0-21 with higher total scores indicating worse sleep quality.	Week 0/Baseline, week 5