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The Use of Transcranial Focused Ultrasound for the Treatment of Neurodegenerative Dementias

Not Applicable
Conditions
Mild Cognitive Impairment
Mild Dementia
Parkinson Disease
Alzheimer Disease
Interventions
Device: Focused Transcranial Ultrasound
Registration Number
NCT04250376
Lead Sponsor
Neurological Associates of West Los Angeles
Brief Summary

The purpose of this open label study is to evaluate longer term tolerability and early efficacy of transcranial ultrasound in the treatment of patients with mild cognitive impairment or dementia.

Detailed Description

The present study is designed as an open label study of patients with mild cognitive impairment (MCI) or dementia to evaluate longer term tolerability and early efficacy of transcranial ultrasound treatment.

Baseline and outcome measures in this study utilize validated tests that are appropriate for repeated measures which are not affected by practice effects. For patients with amnestic predominant cognitive change, the target will be the mesial temporal lobe through a trans temporal scalp window. Targeting will include reference to scalp fiducials based on the obtained MRI and Transcranial Doppler (TCD) waveform confirmation will be obtained because of the ability of TCD to record Doppler signal from the posterior cerebral artery that runs medial to the mesial temporal lobe.

On the day of the ultrasound appointment, patients will undergo ten to thirty minutes of transcranial ultrasound treatment. The sonification device will be aimed at the hippocampus or the putamen and substantia nigra, depending on the predetermined condition. Targeting will include reference to scalp fiducials based on the obtained MRI; confirmation of target accuracy will either be obtained by Doppler waveform confirmation or optical tracking technology which co-registers patient neuroimaging with real space. Patients will undergo 8 total sessions of focused ultrasound. Patients will be evaluated at baseline and upon final ultrasound treatment using the same measures obtained upon entry. Safety and any adverse events will be monitored closely.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
100
Inclusion Criteria
  • CDR stage of at least 0.5 (mild cognitive impairment)
  • At least one pathognomic imaging biomarker of a neurodegenerative process.
Exclusion Criteria
  • Cognitive decline clearly related to an acute illness
  • Subjects unable to give informed consent
  • Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer)
  • Advanced terminal illness
  • Advanced kidney, pulmonary, cardiac or liver failure
  • Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep
  • Subjects with major depressive disorder
  • Subjects with vascular causes of dementia

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TreatmentFocused Transcranial UltrasoundAll patients enrolled will receive transcranial focused ultrasound. Target location is dependent on patient condition.
Primary Outcome Measures
NameTimeMethod
Quick Dementia Rating ScaleBaseline

The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia).

Secondary Outcome Measures
NameTimeMethod
Repeatable Battery Assessment for Neuropsychological Status (RBANS)After final ultrasound (8 weeks from baseline)

RBANS assesses immediate memory, visuospatial skill, language, attention, and delayed memory. Patient performance on each subscale immediate memory, language, attention, visuospatial, and delayed memory are scored relative to validated norms for same-aged peers. A change of 8+ points in the Total Scale score, 11+ points in the Immediate Memory score, 9+ points in the Language score, 4+ points on the Attention score, 14+ points is considered significant for the Visuospatial score, and 10+ points for the Delayed Memory score are considered significant.

Quick Dementia Rating Scale (QDRS)After final ultrasound (8 weeks from baseline)

The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia).

Montreal Cognitive Assessment (MoCA)After final ultrasound (8 weeks from baseline)

The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.

Trial Locations

Locations (1)

Neurological Associates of West LA

🇺🇸

Santa Monica, California, United States

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