Clinical Trials Logo

Clinical Trial Summary

The purpose of the proposed study is to determine the feasibility of brief brain stimulation, using a device called Low Intensity Focused Ultrasound Pulsation (LIFUP), for persons with mild cognitive impairment (MCI) or mild (early-stage) Alzheimer's disease (AD). As a secondary aim, the investigators will explore whether this brief intervention is associated with improvements in cognitive functioning immediately and one week following the intervention. Subjects will be randomly assigned to one of two experimental groups: either the LIFUP administration will be designed to increase the activity of neurons in a certain part of the brain or decrease the activity of neurons. The investigators will study up to 8 subjects with MCI or mild AD. Initially, subjects will undergo a screening assessment with a study physician to determine medical and psychiatric history, establish AD diagnosis, and undergo a blood draw, if standard recent labs for dementia and EKG are unavailable. Subjects that meet criteria and agree to participate in the study will undergo a follow-up visit. In the baseline measurement visit, participants will first undergo neuropsychological testing. Participants will be randomly assigned to one of two LIFUP pulsing paradigms. Participants will then be administered four successive LIFUP treatments while the participants are in a functional magnetic resonance imaging (MRI). Sixty minutes following the administration, participants will undergo a second neuropsychological test. A final follow-up assessment will be administered at one week.


Clinical Trial Description

Alzheimer disease (AD) is a neurodegenerative condition and the most common cause of dementia or a functional impairment in memory and other cognitive abilities. Prior to developing the functional impairment of dementia, patients develop mild cognitive impairment (MCI), which increases the risk for developing the functional impairment of dementia. Deep brain stimulation (DBS) is of interest as a potential therapeutic option for MCI and AD because it can directly target and modulate the activity of brain structures implicated in memory functioning. Recently there have been multiple reports that DBS of different locations within the brain may be effective in improving symptoms characteristic of dementia (e.g., Heschman et al., 2013). For example, Laxton et al. (2010) performed DBS in the fornix/hypothalamus of six persons with AD in a phase I clinical trial. The investigators hypothesized that stimulation of the fornix would alter the activity of the medial temporal memory circuits, and thus delay and/or reverse memory loss. After 6-12 months, the investigators noted improvement or slowing in the progression of AD in some of the research participants, as measured by two commonly-used assessments of global cognitive function. In a recent literature review, Laxton et al. (2013) also described several additional studies demonstrating that DBS of the fornix or nucleus of Meynert or subthalamic nucleus influences the pathologic neurological circuits involved in AD. Four separate groups recently have published reports concluding that ultrasound improves amyloid-β clearance in mouse models and restores memory (e.g., Leinenga & Götz, 2015). This finding raises the question of whether one method of DBS, Low Intensity Focused Ultrasound Pulse (LIFUP), could improve cognition in patients with AD, which is characterized by abnormal deposition of amyloid plaques in brain regions controlling memory and thinking. The use of LIFUP in animal models is well described (Bystritsky et al., 2014). LIFUP is able to penetrate the human skull and reach deep structures within the temporal therapeutic window. The structures that are reachable by LIFUP include the temporal cortices, hippocampus, thalamus, and subthalamic nuclei, all of which are implicated in the pathophysiology of AD. The Food and Drug Administration (FDA) recently approved an investigational device exemption (IDE) to begin a feasibility and safety trial of LIFUP for persons with refractory seizures. Although symptomatic treatments are available for AD, their modest effects are temporary and there is a need for more effective interventions. In the current project, the investigators propose to use the FDA-approved protocol to: 1. Determine the feasibility of a brief LIFUP intervention (four stimulations of 30 seconds each, with 2-minute intervals between each treatment) for persons with MCI or mild (early-stage) AD. 2. As a secondary aim, the investigators will explore whether this brief LIFUP intervention is associated with improvements on neuropsychological measures of cognitive functioning immediately following the intervention. To investigate these aims, subjects with MCI or mild AD will be enrolled. Subjects will be randomized using a single-blind design, to one of two LIFUP pulsing paradigms in which activity of neurons in a certain part of the brain are either increased. Subjects will then be administered four successive LIFUP treatments while the subjects are in a functional magnetic resonance imaging (MRI). Neuropsychological assessments will be performed at baseline, immediately after LIFUP is administered, and one week following the conclusion of the visit. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03347084
Study type Interventional
Source University of California, Los Angeles
Contact
Status Active, not recruiting
Phase N/A
Start date November 10, 2018
Completion date October 2023

See also
  Status Clinical Trial Phase
Completed NCT04044495 - Sleep, Rhythms and Risk of Alzheimer's Disease N/A
Completed NCT04079803 - PTI-125 for Mild-to-moderate Alzheimer's Disease Patients Phase 2
Terminated NCT03052712 - Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies N/A
Recruiting NCT04520698 - Utilizing Palliative Leaders In Facilities to Transform Care for Alzheimer's Disease N/A
Active, not recruiting NCT04606420 - Can Lifestyle Changes Reverse Early-Stage Alzheimer's Disease N/A
Recruiting NCT05820919 - Enhancing Sleep Quality for Nursing Home Residents With Dementia - R33 Phase N/A
Terminated NCT03672474 - REGEnLIFE RGn530 - Feasibility Pilot N/A
Completed NCT03430648 - Is Tau Protein Linked to Mobility Function?
Recruiting NCT04522739 - Spironolactone Safety in African Americans With Mild Cognitive Impairment and Early Alzheimer's Disease Phase 4
Recruiting NCT05557409 - A Study to Assess the Efficacy and Safety of AXS-05 in Subjects With Alzheimer's Disease Agitation Phase 3
Recruiting NCT04949750 - Efficacy of Paper-based Cognitive Training in Vietnamese Patients With Early Alzheimer's Disease N/A
Recruiting NCT05288842 - Tanycytes in Alzheimer's Disease and Frontotemporal Dementia
Completed NCT06194552 - A Multiple Dose Study of the Safety and Pharmacokinetics of NTRX-07 Phase 1
Completed NCT03239561 - Evaluation of Tau Protein in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants Early Phase 1
Completed NCT03184467 - Clinical Trial to Evaluate the Efficacy and Safety of GV1001 in Alzheimer Patients Phase 2
Active, not recruiting NCT03676881 - Longitudinal Validation of a Computerized Cognitive Battery (Cognigram) in the Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease
Terminated NCT03487380 - Taxonomic and Functional Composition of the Intestinal Microbiome: a Predictor of Rapid Cognitive Decline in Patients With Alzheimer's Disease N/A
Completed NCT05538455 - Investigating ProCare4Life Impact on Quality of Life of Elderly Subjects With Neurodegenerative Diseases N/A
Recruiting NCT05328115 - A Study on the Safety, Tolerability and Immunogenicity of ALZ-101 in Participants With Early Alzheimer's Disease Phase 1
Completed NCT05562583 - SAGE-LEAF: Reducing Burden in Alzheimer's Disease Caregivers Through Positive Emotion Regulation and Virtual Support N/A