Back to results

Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Aduhelm Therapy.

Primary Purpose

Mild Cognitive Impairment, Alzheimer Disease 1

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Aducanumab

Exablate Model 4000 Type 2

About this trial

This is an interventional device feasibility trial for Mild Cognitive Impairment

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Able and willing to give informed consent
Probable mild cognitive impairment due to AD
Modified Hachinski Ischemia Scale (MHIS) score of <= 4
Mini Mental State Exam (MMSE) scores > 21+.
Short form Geriatric Depression Scale (GDS) score of <= 7
IAmyloid PET scan consistent with the presence of β-amyloid (A+)
Able to communicate sensations during the Exablate MRgFUS procedure
Able to attend all study visits (i.e., life expectancy of 1 year or more)

Exclusion Criteria:

MRI findings:
Significant cardiac disease or unstable hemodynamic status
History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage
Known cerebral or systemic vasculopathy
Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2)
A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q)
Known sensitivity/allergy to gadolinium(gadobutrol), DEFINITY or its components, or 18F-florbetaben.
Known hypersensitivity to DEFINITY or its components.
Any contraindications to MRI scanning
Untreated, uncontrolled sleep apnea
History of epilepsy.
Impaired renal function
Does not have a reliable caregiver
Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research.
Respiratory: chronic pulmonary disorders
History of clinically significant recent drug or alcohol use disorder who may be at higher risk for seizure or infection.
Positive human immunodeficiency virus (HIV) which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.
Potential blood-borne infections, which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.

Sites / Locations

West Virginia University Rockefeller Neuroscience InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Infusion plus Exablate BBBO Treatment

Arm Description

Intravenous infusion of Aducanumab every 4 weeks followed by blood brain barrier opening by FUS.

Outcomes

Primary Outcome Measures

Treatment intervention related adverse events

The total number of adverse events following each treatment through end of the study

Treatment intervention related serious adverse events

The total number of serious adverse events following each treatment through end of the study

Secondary Outcome Measures

Beta-Amyloid plaques within the brain

Beta-Amyloid uptake value measured by Amyloid PET scan

Cognitive performance (ADAS COG 11)

Change in cognitive performance using the Alzheimer's Disease Assessment Cognitive Subscale, rating scores from 0-70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.

Cognitive performance (MMSE)

Change in cognitive performance using the Mini Mental Status Exam, rating scores from 0-30. 25 or higher being classed as normal. A score below 24 is considered abnormal, indicating possible cognitive impairment.

Full Information

NCT ID

NCT05469009

First Posted

July 19, 2022

Last Updated

August 17, 2022

Sponsor

Ali Rezai

Collaborators

InSightec

1. Study Identification

Unique Protocol Identification Number

NCT05469009

Brief Title

Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Aduhelm Therapy.

Official Title

Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Aduhelm Therapy.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 14, 2022 (Actual)

Primary Completion Date

July 2029 (Anticipated)

Study Completion Date

July 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Ali Rezai

Collaborators

InSightec

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to assess the safety and feasibility of administering standard of care monthly Aduhelm (Aducanumab) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).

Detailed Description

The primary objectives of this study is to evaluate the safety and feasibility of BBBO (blood-brain barrier opening) using the Exablate Model 4000 Type 2 in the setting of standard aducanumab therapy among patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD) with confirmed β-amyloid, who are eligible for aducanumab infusion therapy, and to also evaluate the safety of the BBO procedure through patient examination (neurological and cognitive/behavioral) and MRI assessments during the treatment and follow-up. The secondary objectives of this study is to determine the effect of BBBO in patients with MCI or mild AD treated with aducanumab on brain β-amyloid plaque measured by amyloid positron emission tomography (PET), as well as to assess the clinical impact of BBBO with standard aducanumab therapy, if any, as assessed with ADAS Cog 11 and MMSE over time following BBBO.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mild Cognitive Impairment, Alzheimer Disease 1

7. Study Design

Primary Purpose

Device Feasibility

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Infusion plus Exablate BBBO Treatment

Arm Type

Experimental

Arm Description

Intravenous infusion of Aducanumab every 4 weeks followed by blood brain barrier opening by FUS.

Intervention Type

Drug

Intervention Name(s)

Aducanumab

Other Intervention Name(s)

Aduhelm

Intervention Description

Standard aducanumab therapy will be given by intravenous infusion every 4 weeks for 6 cycles with blood brian barrier opening

Intervention Type

Device

Intervention Name(s)

Exablate Model 4000 Type 2

Other Intervention Name(s)

Focused Ultrasound

Intervention Description

The Exablate Model 4000 will be utilized for the BBBO (blood-brain barrier opening) after each cycle of Aducanumab administered per label.

Primary Outcome Measure Information:

Title

Treatment intervention related adverse events

Description

The total number of adverse events following each treatment through end of the study

Time Frame

From baseline, up to 5 year post last treatment

Title

Treatment intervention related serious adverse events

Description

The total number of serious adverse events following each treatment through end of the study

Time Frame

From baseline, up to 5 year post last treatment

Secondary Outcome Measure Information:

Title

Beta-Amyloid plaques within the brain

Description

Beta-Amyloid uptake value measured by Amyloid PET scan

Time Frame

From baseline, up to 5 year post last treatment

Title

Cognitive performance (ADAS COG 11)

Description

Time Frame

From baseline, up to 5 year post last treatment

Title

Cognitive performance (MMSE)

Description

Time Frame

From baseline, up to 5 year post last treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Able and willing to give informed consent Probable mild cognitive impairment due to AD Modified Hachinski Ischemia Scale (MHIS) score of <= 4 Mini Mental State Exam (MMSE) scores > 21+. Short form Geriatric Depression Scale (GDS) score of <= 7 IAmyloid PET scan consistent with the presence of β-amyloid (A+) Able to communicate sensations during the Exablate MRgFUS procedure Able to attend all study visits (i.e., life expectancy of 1 year or more) Exclusion Criteria: MRI findings: Significant cardiac disease or unstable hemodynamic status History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage Known cerebral or systemic vasculopathy Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2) A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q) Known sensitivity/allergy to gadolinium(gadobutrol), DEFINITY or its components, or 18F-florbetaben. Known hypersensitivity to DEFINITY or its components. Any contraindications to MRI scanning Untreated, uncontrolled sleep apnea History of epilepsy. Impaired renal function Does not have a reliable caregiver Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research. Respiratory: chronic pulmonary disorders History of clinically significant recent drug or alcohol use disorder who may be at higher risk for seizure or infection. Positive human immunodeficiency virus (HIV) which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis. Potential blood-borne infections, which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ali Rezai, MD, FAANS

Phone

3042933368

ali.rezai@hsc.wvu.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Marc Haut, PhD, ABPP-CN

Phone

304-293-6276

mhaut@hsc.wvu.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ali Rezai, MD, FAANS

Organizational Affiliation

WVU Rockerfeller Neuroscience Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

West Virginia University Rockefeller Neuroscience Institute

City

Morgantown

State/Province

West Virginia

ZIP/Postal Code

26506

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Padma Tirumalai, PhD

Phone

304-293-4999

ptirumalai@hsc.wvu.edu

First Name & Middle Initial & Last Name & Degree

Ali Rezai

12. IPD Sharing Statement

Learn more about this trial

Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Aduhelm Therapy.

We'll reach out to this number within 24 hrs