Lymphatic System Health in Alzheimer's Disease

September 26, 2022 updated by: Neurological Associates of West Los Angeles
This study hopes to investigate differences in lymphatic health of patients with Alzheimer's disease by analyzing diffusion-weight images in conscious and sleep states. Dexmedetomidine is a short-acting agent that facilitates a sedated state characterized by slow waves and inhibition of norepinephrine. Conceptually, dexmedetomidine may be preferred to other agents, because it is a short-acting norepinephrine blocker, which could mimic slow wave sleep architecture, opening interstitial spaces, and facilitating plaque removal. Dexmedetomidine may also be preferred given its safety profile among the elderly and acutely ill compared to other anesthetic agents. Sleep will be induced with dexmedetomidine, and interstitial fluid convection will be assessed by measuring free-water diffusion imaging. Freewater diffusion imaging separates out the contributions of extracellular free water and water in the vicinity of cellular tissue; it is used to evaluate abnormalities in extracellular space, such as neuroinflammation, which may contribute to long-term cellular degeneration. This method of analysis could be useful in assessing the lymph systems ability to remove extracellular debris.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The present study is designed as a prospective data analysis of lymphatic system health in Alzheimer's patients and controls. For Phase I trail, 50 patients of any gender with an age range of 18 to 90 who have undergone the outlined procedure will be recruited for inclusion. Patients will be examined by the principle investigator. All patients will complete neurocognitive testing (QDRS and RBANS) to assess cognitive impairment. A CDR score of 1 or above will be considered dementia. Lumbar punctures will be used to determine Alzheimer's disease status. Patients will be offered the option of participating in the study and provided informed consent for neuroimaging. The subjects will have three fMRI scans: structural T1 and two NOODI DTI scans. The scans take around 45 minutes at no charge to the patients. The dexmedetomidine will be given to the patient after the first DTI scan. The dexmedetomidine dosage will be congruent with patient height, weight, and medical history. This medication will be administered sublingually using an LMA Intranasal Mucosal Atomization Device, which allows the medication to be administered in the form of a spray. Patients will be instructed to keep the medication in their mouth for about 2 minutes, or until fully absorbed. Pulse oximetry and blood pressure will be monitored throughout the duration of treatment. After the subject is asleep, the second DTI scan will be done.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90024
        • Westwood Open MRI
      • Santa Monica, California, United States, 90403
        • Neurological Associates of West Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • In order for a subject to be considered for this study, the subject must be willing to comply with the study protocol. They must be between 18 and 90 years old. They must complete neurocognitive testing to assess cognitive impairment (QDRS and RBANS).

Exclusion Criteria:

  • Advanced stages of any terminal illness or any active cancer that requires chemotherapy
  • Hepatic impairment
  • Significant cytopenia
  • Cardiovascular, cerebrovascular, and peripheral vascular arterial thrombosis
  • Women who are pregnant, may become pregnant, or are breastfeeding
  • Any counter indications to dexmedetomidine
  • Subjects unable to give informed consent or in vulnerable categories, such as prisoners

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dexmedetomidine
All patients will complete neurocognitive testing inclusive of the Quick Dementia Rating Scale (QDRS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)) to assess cognitive impairment. A Clinical Dementia Rating (CDR) score of 1 or above will be considered dementia. Lumbar punctures will be used to determine Alzheimer's disease status.The subjects will have three fMRI scans: structural T1 and two NOODI DTI scans. The dexmedetomidine will be given to the patient after the first DTI scan with a dosage that will be congruent with patient height, weight, and medical history.
Drug: Dexmedetomidine
This medication will be administered sublingually using an LMA Intranasal Mucosal Atomization Device, which allows the medication to be administered in the form of a spray. Patients will be instructed to keep the medication in their mouth for about 2 minutes, or until fully absorbed. Pulse oximetry and blood pressure will be monitored throughout the duration of treatment. After the subject is asleep, the second DTI scan will be done.
Other Names:
  • Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
T1 fMRI Imaging
Time Frame: Before dexmedetomidine
T1-data was collected as a sagittal MPRAGE sequence. T1 images are corrected for field biasing and then skull stripped and linearly registered to standard MNI space. Each patients' T1 image is segmented into 100 cortical and 15 subcortical areas using the Harvard-Oxford Cortical and Subcortical structural atlas. Mean volume is computed for each of these regions for each patient, which can be used for quantitative comparison.
Before dexmedetomidine
T1 fMRI Imagine
Time Frame: Immediately following administration of dexmedetomidine
T1-data was collected as a sagittal MPRAGE sequence. T1 images are corrected for field biasing and then skull stripped and linearly registered to standard MNI space. Each patients' T1 image is segmented into 100 cortical and 15 subcortical areas using the Harvard-Oxford Cortical and Subcortical structural atlas. Mean volume is computed for each of these regions for each patient, which can be used for quantitative comparison.
Immediately following administration of dexmedetomidine
Diffusion Tensor Imaging
Time Frame: Before dexmedetomidine administration
Diffusion tensor imaging is acquired through diffusion weighted imaging (DWI)-a magnetic resonance techniques that evaluate water diffusion in terms of diffusion constants and diffusion anisotropy. From the acquired DWI, diffusion tensor imaging (DTI) allows us to model the degree of anisotropy and the structural orientation in a quantitative fashion. These DTI fractional anisotropy values will be compared pre and post-treatment.
Before dexmedetomidine administration
Diffusion Tensor Imaging
Time Frame: Immediately following administration of dexmedetomidine
Diffusion tensor imaging is acquired through diffusion weighted imaging (DWI)-a magnetic resonance techniques that evaluate water diffusion in terms of diffusion constants and diffusion anisotropy. From the acquired DWI, diffusion tensor imaging (DTI) allows us to model the degree of anisotropy and the structural orientation in a quantitative fashion. These DTI fractional anisotropy values will be compared pre and post-treatment.
Immediately following administration of dexmedetomidine

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D
Time Frame: 1 week prior to dexmedetomidine
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.
1 week prior to dexmedetomidine
Quick Dementia Rating Scale (QDRS)
Time Frame: 1 week prior to dexmedetomidine
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).
1 week prior to dexmedetomidine

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neurological Associates of West Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 10, 2021

Primary Completion (Anticipated)

December 10, 2022

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

December 17, 2019

First Submitted That Met QC Criteria

December 18, 2019

First Posted (Actual)

December 19, 2019

Study Record Updates

Last Update Posted (Actual)

September 28, 2022

Last Update Submitted That Met QC Criteria

September 26, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20190858

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Data from this study will not be made publicly available due to ethical and privacy concerns. Anonymized data will be available upon reasonable request from any qualified investigator.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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