Low Intensity Focused Ultrasound for Mild Cognitive Impairment and Mild Alzheimer's Disease (LIFUP-MCIAD)
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ClinicalTrials.gov Identifier: NCT05417555 |
Recruitment Status :
Recruiting
First Posted : June 14, 2022
Last Update Posted : March 20, 2024
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The goal of this study is to investigate whether Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting a part of the brain involved in memory will have an affect on brain activity and whether it may improve memory in people with Mild Cognitive Impairment and Mild Alzheimer's Disease.
The main questions the study seeks to answer are:
- Can LIFUP increase brain activity in the targeted area?
- Can LIFUP improve memory in people with MCI and mild AD?
- Can LIFUP improve connectivity of memory networks in the brain?
Participants in this study will complete MRIs and memory testing, and receive Low Intensity Focused Ultrasound to a part of their brain involved in memory (the entorhinal cortex).
Condition or disease | Intervention/treatment | Phase |
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Mild Cognitive Impairment Amnestic Mild Cognitive Disorder Deep Brain Stimulation Mild Alzheimer's Disease | Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP) | Not Applicable |
This is a proof of concept trial of Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting the entorhinal cortex in patients with amnestic MCI and Mild Alzheimer's Disease. Participation in the study will entail one Zoom intake session, three in-person sessions and three remote Zoom follow-up sessions over the course of about five weeks. The in-person sessions will take about 5 hours for the first and 3 hours for the following two. The Zoom intake session will take 1-2 hours, and the Zoom follow-up sessions will take about 2 hours each. Participants will be asked to complete questionnaires and tests of learning and memory, have their blood drawn, undergo painless ultrasound stimulation to a part of their brain related to memory, and complete MRI scans of their brain. LIFUP will be administered inside of the MRI scanner, so that we can measure changes in brain activity in real-time.
At the start of the study, you will be randomly assigned to one of four different groups that determines the amount of LIFUP stimulation you will receive. You have an equal chance of being assigned to each group. Participants in one of the three active stimulation groups will receive either 1 dose, 2 doses, or 3 doses of LIFUP at their second in-person session, and will receive the same dose again at their third in-person session. Participants in the placebo group will receive no LIFUP stimulation at either MRI/LIFUP session (in-person visits 2 and 3). However, if at the end of our study, the treatment has been shown to be effective, and you were a placebo subject, we will offer you a free session using the most effective dose.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 144 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Subjects are randomly assigned to one of four treatment dosage conditions: 0, 1, 2 or 3 treatments at each MRI-LIFUP session. After 2 weeks, a second dose is administered with the same dosage level for each subject. Memory assessment occurs once at baseline and remotely after each treatment at the onset of the optimal time window (48 hours) for LIFUP-induced change based on prior data. Finally, after 2 weeks, memory is again assessed. Alternate forms are used for the primary outcome measures to avoid practice effects. |
Masking: | Double (Participant, Outcomes Assessor) |
Masking Description: | Participants and the participants' caregivers will be blinded to arm assignment. Additionally, the person administering memory testing will be blinded to assignment. |
Primary Purpose: | Treatment |
Official Title: | Modulation of Hippocampal Circuitry and Memory Function With Focused Ultrasound in Amnestic MCI |
Actual Study Start Date : | September 1, 2022 |
Estimated Primary Completion Date : | July 31, 2026 |
Estimated Study Completion Date : | July 31, 2026 |
Arm | Intervention/treatment |
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Active Comparator: LIFUP Dose Group 1
Administration of low intensity focused ultrasound (LIFUP) dose level 1 to the entorhinal cortex.
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Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)
Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)
Other Names:
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Active Comparator: LIFUP Dose Group 2
Administration of low intensity focused ultrasound (LIFUP) dose level 2 to the entorhinal cortex.
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Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)
Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)
Other Names:
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Active Comparator: LIFUP Dose Group 3
Administration of low intensity focused ultrasound (LIFUP) dose level 3 to the entorhinal cortex.
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Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)
Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)
Other Names:
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Sham Comparator: Sham LIFUP
No administration of LIFUP. The device will be affixed to the user's head but not turned on. Additionally, if at the end of the study, the treatment has been shown to be effective, placebo subjects will be offered a free session using the optimally effective dose, if they consented to being contacted for this purpose. |
Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)
Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)
Other Names:
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- Change in Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain [ Time Frame: 40 minutes ]Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre and post sonication.
- Changes in BOLD-related functional connectivity from baseline in fMRI brain scan to 40 minutes. [ Time Frame: 40 minutes ]
Primary outcomes for proof of mechanism that may be depicted in the fMRI scans may include changes in BOLD-related functional connectivity increases within the DMN including regions functionally connected to the target.
BOLD data will be collected before, during, and following LIFUP sonication. Analyses will assess any changes in BOLD signal in the brain following sonication.
- Change in Brief Visual Memory Test Scores [ Time Frame: 48 hours ]Potential LIFUP-related changes in memory will be assessed via neuropsychological assessments including the Brief Visual Memory Tests (BVMT). Scores range from 0 to 12 and reflect recent, long-term learning, with higher scores indicating better learning.
- Change in Verbal Learning Test Scores [ Time Frame: 48 hours ]Potential LIFUP-related changes in memory will be assessed via the Rey Auditory Verbal Learning Test (RAVLT) neuropsychological assessment. The RAVLT involves providing participants with 15 unrelated words and asking them to recall the word list. There are 5 trials designed to determine short-term memory and then a 20 minute delay to assess long-term memory. The total words correct in both the short- and long-term trials are used as outcome measures.
- Post-hoc biomarker analysis of APOE-4 status as a predictor of tFUS efficacy [ Time Frame: Baseline (pre-LIFUP) ]Biomarker post hoc analysis will determine the degree to which blood based biomarkers predict the level of effectiveness of tFUS. Samples are collected before LIFUP is administered.
- Post-hoc biomarker analysis of plasma AB42/40 ratio as a predictor of tFUS efficacy [ Time Frame: Baseline (pre-LIFUP) ]
Biomarker post hoc analysis will determine the degree to which blood based biomarkers predict the level of effectiveness of tFUS. Samples are collected before LIFUP is administered.
An Aβ42/40 ratio <0.160 suggests a higher-than-normal risk of having of AD and is warranted to support a diagnosis of AD (West et al 2021).
- Post-hoc biomarker analysis of plasma ptau as a predictor of tFUS efficacy [ Time Frame: Baseline (pre-LIFUP) ]Biomarker post hoc analysis will determine the degree to which blood based biomarkers predict the level of effectiveness of tFUS. Samples are collected before LIFUP is administered.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 50 Years to 90 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
- Amnestic MCI or Mild Alzheimer's diagnosis
- Age 50-90
- English-speaking
- Right-handed
- Ability to provide informed consent
- Normal or corrected-to-normal hearing and vision
Exclusion Criteria
GENERAL
- Participation in another clinical trial
- Active use of immunotherapeutic medications for cognition (Aduhelm)
- Moderate to Severe Alzheimer's
- Inability to provide informed consent
MRI-Related:
- Weight exceeding 275 pounds
- Pregnancy, suspicion of pregnancy, or attempting to become pregnant
- Claustrophobia
- Difficulties during previous MRIs
- Top permanent retainer (bottom only is okay), 5 or more non-removable gold-teeth, metal braces, top spacers, and/or palate expanders
- Any of the following implants: Cardiac Pacemaker, Aneurysm clips, Cochlear implants, Defibrillator, Electrodes or wires, Magnetically-activated device, Spinal cord stimulator, Infusion or insulin pumps, Implanted drug infusion device, Deep brain stimulation device
- Non-removable hairpieces, hairpiece extensions, and/or piercings
- Facial tattoos or permanent makeup
- Metal implants that are MR-incompatible, or where participant is unable to provide sufficient information to determine MR compatibility
- Previous injury by metallic foreign body (e.g., bullet, BB, shrapnel) where the object entered the body and participant lacks doctor's confirmation that it was fully removed
Medical:
- Diagnosis of one or more of the following neurological disorders: Parkinson's disease, Lou Gehrig's disease (ALS), Multiple sclerosis, Cerebral Palsy
- Diagnosis of one or more of the following genetic disorders: Cystic Fibrosis, Sickle Cell Disease
- Diagnosis of one or more of the following psychiatric disorders: Bipolar, Psychosis
- Psychiatric illness that has not been controlled for at least one year (if controlled >1 year, with or without medication, they are not exclusionary)
- Severe lung, liver, heart, and/or kidney disease/s (e.g., heart failure, liver failure, and etc...)
- Diagnosis of thyroid disorder or change of thyroid medication dose within the last year
- Cancer treatment/s with chemotherapy and/or radiation to head and neck, or stage 4 (metastatic) cancer
- Autoimmune disorder or viral infection such as HIV, COVID 19, or hepatitis C that has caused current problems with cognition/memory
- History of substance abuse in the past year
- History of stroke (Transient ischemic attack / mini-stroke not exclusionary if symptoms lasted <1 week)
- History of 2 or more seizures or diagnosis of epilepsy, unless the seizures occurred prior to age 5 alongside a fever.
- History of brain tumor, brain aneurysm, brain hemorrhage, or subdural hematoma (transient ischemic attack not exclusionary)
- Head injury that resulted in loss of consciousness lasting >30 minutes, cognitive issues lasting >18 months, and/or brain abnormalities visible in CT or MRI scan
- Uncontrolled high blood pressure or diabetes
- Heart attack within the last year
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05417555
Contact: Bianca H Dang | (310) 794-0077 | tfus@mednet.ucla.edu | |
Contact: Natalie M Rotstein | (310) 794-0077 | tfus@mednet.ucla.edu |
United States, California | |
UCLA Semel Institute for Neuroscience and Behavior | Recruiting |
Los Angeles, California, United States, 90024 | |
Contact: Bianca H Dang 310-794-0077 tfus@mednet.ucla.edu | |
Contact: Natalie M Rotstein 3107940077 tfus@mednet.ucla.edu | |
Principal Investigator: Taylor P Kuhn, PhD | |
Principal Investigator: Susan Y Bookheimer, PhD |
Principal Investigator: | Susan Y Bookheimer, PhD | UCLA Psychiatry & Biobehavioral Sciences | |
Principal Investigator: | Taylor P Kuhn, PhD | UCLA Psychiatry & Biobehavioral Sciences |
Publications:
Responsible Party: | Taylor Kuhn, Principal Investigator, University of California, Los Angeles |
ClinicalTrials.gov Identifier: | NCT05417555 |
Other Study ID Numbers: |
IRB#21-000995 1R01AG073480-01 ( U.S. NIH Grant/Contract ) IRB#21-000995 ( Other Identifier: UCLA ) |
First Posted: | June 14, 2022 Key Record Dates |
Last Update Posted: | March 20, 2024 |
Last Verified: | March 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | Yes |
Device Product Not Approved or Cleared by U.S. FDA: | Yes |
Product Manufactured in and Exported from the U.S.: | No |
deep brain stimulation (DBS) transcranial focused ultrasound stimulation (tFUS) memory low-intensity focused ultrasound pulsation (LIFUP) fMRI mild cognitive impairment |
mci noninvasive brain stimulation (NIBS) ultrasound Alzheimer's Disease Mild Alzheimer's |
Alzheimer Disease Cognitive Dysfunction Cognition Disorders Dementia Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |