Deep Brain Stimulation with LIFUP for Mild Cognitive Impairment and Mild Alzheimer's Disease

NCT03347084 | Completed DMC FDA Device

• 1 other identifier: 16-001314
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Brain Imaging; Mild Cognitive Impairment; Alzheimer Disease; Deep Brain Stimulation

Keywords

DBS; brain imaging; Memory; fMRI

Outcome Measures

Primary Outcomes (1)

• Change from baseline in fMRI brain scan to 40 minutes.

  Functional MRI of the brain will be obtained throughout the LIFUP session for the purposes of image acquisition.

  40 Minutes

Secondary Outcomes (3)

• Change from baseline in Hopkins Verbal Learning Test-Revised45 (HVLT-R)

  60 Minutes, 1 Week

• Change from baseline in Brief Visual Memory Test-Revised

  60 Minutes, 1 Week

• Change from baseline in Geriatric Anxiety Inventory (GAI)

  60 Minutes, 1 Week

Study Arms (2)

Excitation

ACTIVE COMPARATOR

Excitation Paradigm: LIFUP excites the activity of hippocampal neurons.

Device: Excitation

Inhibition

ACTIVE COMPARATOR

Inhibition Paradigm: LIFUP inhibits the activity of hippocampal neurons.

Device: Inhibition

Interventions

Excitation DEVICE

Administration of LIFUP, a method of deep brain stimulation, according to excitation paradigms using the following parameters: Tone Burst Duration = 50ms; Pulse Repetition Frequency = 10Hz; ISPTA = 720 mW/cm2. Four treatments of thirty seconds each, with two-minute intervals between treatment (20 minutes, approximately)

Also known as: Low Intensity Focused Ultrasound Pulse

Excitation

Inhibition DEVICE

Administration of LIFUP, a method of deep brain stimulation, according to inhibition paradigms using the following parameters: Tone Burst Duration = 50ms and Pulse Repetition Frequency = 10Hz. Four treatments of thirty seconds each, with two-minute intervals between treatment (20 minutes, approximately)

Also known as: Low Intensity Focused Ultrasound Pulse

Inhibition

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mild cognitive impairment or mild (early-stage) AD diagnosis through medical record review
• Agreement to participate in a clinical and brain imaging study.
• Age 55 years or older.
• No significant cerebrovascular disease as determined by a modified Ischemic Score of ≤ 4.
• Availability of a study partner (next of kin, family member) to attend all visits and to provide surrogate consent should it be determined that the participant does not have capacity.
• Adequate visual and auditory acuity to allow neuropsychological testing.
• Screening laboratory tests and ECG without significant abnormalities that might interfere with the study.
• Use of cholinesterase inhibitors for AD (Aricept, Namenda, etc.) will be allowed as long as the participant has been on a stable dose for at least two months.
• There must be a family member or caregiver available to make sure the participant gives informed consent, and in case the participant develops cognitive impairment that interferes with independent study participation.

You may not qualify if:

• Evidence of any other major neurologic or other physical illness that could produce cognitive deterioration, except for mild cognitive impairment (MCI) and any history of stroke or diabetes.
• History of myocardial infarction within the previous year or unstable cardiac disease.
• Uncontrolled hypertension (systolic BP \> 170 or diastolic BP \> 100), history of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer.
• Major psychiatric disorders, such as bipolar disorder or schizophrenia, or persons with current untreated major depression
• Current diagnosis or significant history of alcoholism or drug dependence.
• Use of any investigational drugs within the previous month or longer, depending on the drug's half-life.
• Contraindication for fMRI scan (e.g. metal in body, claustrophobia).

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Semel Institute

Los Angeles, California, 90095, United States

Location

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Related Links

• Analysis Group, Oxford, UK. FMRIB Software Library v5.0.

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Microscopy, Fluorescence, Multiphoton

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Microscopy, Fluorescence; Microscopy; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Nonlinear Optical Microscopy; Investigative Techniques

Study Officials

• Taylor P Kuhn, PhD

  UCLA Longevity Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants and the participants' caregivers will be blinded to arm assignment.
• Purpose: DEVICE FEASIBILITY
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants will be randomly assigned to one of two LIFUP pulsing paradigms: one that excites the activity of hippocampal neurons ("Paradigm A"), or a second that inhibits them ("Paradigm B"). The participants will then be administered four successive LIFUP treatments while the participants are in a functional magnetic resonance imaging (MRI).

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 20, 2017
• Study Start: November 10, 2018
• Primary Completion: March 31, 2023
• Study Completion: October 1, 2023
• Last Updated: September 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)