Clinical trial NCT04205539: Lymphatic System Health in Alzheimer's Disease
Official title: Lymphatic System Health in Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: dexmedetomidine
lymphatic system
Lead sponsor: Neurological Associates of West Los Angeles
Sponsor class: OTHER
First posted: 2019-12-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: T1 fMRI Imaging
timeFrame: Before dexmedetomidine
measure: T1 fMRI Imagine
timeFrame: Immediately following administration of dexmedetomidine
measure: Diffusion Tensor Imaging
timeFrame: Before dexmedetomidine administration
measure: Diffusion Tensor Imaging
timeFrame: Immediately following administration of dexmedetomidine
Secondary outcomes:
measure: Repeatable Battery Assessment of Neuropsychological Status (RBANS) versions A-D
timeFrame: 1 week prior to dexmedetomidine
measure: Quick Dementia Rating Scale (QDRS)
timeFrame: 1 week prior to dexmedetomidine
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Westwood Open MRI
state: California
city: Santa Monica
country: United States
facility: Neurological Associates of West Los Angeles
state: California
Study officials:
affiliation: The Neurological Associates of West Los Angeles
name: Sheldon Jordan, MD
role: PRINCIPAL_INVESTIGATOR
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