Investigating LIFUP in Anhedonic Depression
- Conditions
- AnhedoniaDepression
- Interventions
- Device: Low Intensity Focused Ultrasound Pulsation (LIFUP)
- Registration Number
- NCT06285474
- Lead Sponsor
- University of California, Los Angeles
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
-
• 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
-
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sham Caudate Low Intensity Focused Ultrasound Pulsation (LIFUP) 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. Active Caudate Low Intensity Focused Ultrasound Pulsation (LIFUP) 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.
- Primary Outcome Measures
Name Time Method Change in Patient health questionnaire-14 self report measure (PHQ-14) from baseline Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 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.
Change in Positive valence systems scale-21 self report measure (PVSS-21) from baseline Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 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.
Changes in MRI images from Pre-scan to week 5 Pre-scan, 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.Change in Ecological momentary assessment (EMA) from W0/Baseline Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 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.
- Secondary Outcome Measures
Name Time Method Changes in digital behavioral phenotype sleep measurement Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 Apple watch \& phone sensor metrics of sleep.
Changes in digital behavioral phenotype physical activity measurement Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 Apple watch \& phone sensor metrics of physical activity.
Changes in heart rate Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 Apple watch \& phone sensor metrics of heart rate.
Changes in heart rate variability Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 Apple watch \& phone sensor metrics of heart rate variability.
Changes in respiratory rate Week 0, Pre-scan, Baseline, week 1, week 2 week 3, week 4, week 5 Apple watch \& phone sensor metrics of respiratory rate.
changes in World Health Organization (WHO) -5 Wellbeing index score from W0/Baseline to end of study Week 0/Baseline, week 5 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.
changes in Pittsburgh Sleep Quality Index (PSQI) score from W0/Baseline to end of study Week 0/Baseline, week 5 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.
Trial Locations
- Locations (1)
University of California Los Angeles
🇺🇸Los Angeles, California, United States