Lymphatic System Health in Alzheimer's Disease

NCT04205539 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 20190858
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

dexmedetomidine; lymphatic system

Outcome Measures

Primary Outcomes (4)

• T1 fMRI Imaging

  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

  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

  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

  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 Outcomes (2)

• Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D

  1 week prior to dexmedetomidine

• Quick Dementia Rating Scale (QDRS)

  1 week prior to dexmedetomidine

Study Arms (1)

Dexmedetomidine

EXPERIMENTAL

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

Interventions

Dexmedetomidine DRUG

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.

Also known as: Precedex

Dexmedetomidine

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Neurological Associates of West Los Angeles: lead

Study Sites (2)

Westwood Open MRI

Los Angeles, California, 90024, United States

Location

Neurological Associates of West Los Angeles

Santa Monica, California, 90403, United States

Location

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MeSH Terms

Conditions

Alzheimer Disease

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sheldon Jordan, MD

  The Neurological Associates of West Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 scans take around 45 minutes at no charge to the patients. The dexmedetomidine will be given to the patient after the first DTI scan; this dosage will be congruent with patient height, weight, and medical history. After the subject is asleep, the second DTI scan will be done.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 19, 2019
• Study Start: December 10, 2021
• Primary Completion: December 10, 2022
• Study Completion: December 1, 2023
• Last Updated: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)