Hypertension, Brain Clearance, and Markers of Neurodegeneration

Hypertension Clinical Trial

Official title:

Hypertension, Brain Clearance, and Markers of Neurodegeneration

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05785871
• Other study ID #: 19-05020073
• Secondary ID: 5R01NS104364-03
• Status: Active, not recruiting
• Start date: November 18, 2020
• Est. completion date: April 30, 2024

Study information

• Verified date: February 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The purpose of this research study is to measure cerebrospinal fluid (CSF) clearance in subjects with and without high blood pressure. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Impaired removal of proteins from the aging brain causes their buildup and may contribute to an increased risk for Alzheimer's disease. It is also suspected that clearance may be related to the health of vessels carrying the blood throughout the brain. It is known that high blood pressure damages blood vessels and thus may impair clearance. In this project we will examine if having high blood pressure is related to impaired brain clearance and whether treating high blood pressure improves clearance and reduces buildup of Alzheimer's disease-related proteins.

Participants will be asked to undergo a medical examination, testing of memory, brain imaging (both magnetic resonance and positron emission tomography, and spinal tap at the beginning of the study and 1 -2 years later.

Description:

Over 5 years the investigator will conduct a 24-month longitudinal study of 80 cognitively healthy subjects 60-80 years old, classified at baseline into the following groups: 1) Normotensive NT (n=20), 2) Controlled hypertension C-HTN (n=20), 3) Uncontrolled hypertension or Untreated hypertension UU-HTN (n=30).

For subjects in the NT and C-HTN groups this will be an observational longitudinal study with clinical, imaging and CSF (cerebrospinal fluid) assessment at baseline and 24 month follow-up, with 3 visits to monitor BP (blood pressure) in-between (both at the office and using home BP monitoring). Subjects in the UU-HTN group after having completed their baseline evaluation will be referred for a further evaluation of HTN (hypertension) and an intervention. Intervention: the initiation of treatment or treatment modification to achieve the SBP (systolic blood pressure) goal of <140 mmHg. Subjects will be referred to their physician or, in case they do not have one, to the study cardiologist for treatment according to current guidelines. Imaging at 0 and 24 month consist of MRI (magnetic resonance imaging) with ASL (arterial spin labeling) and brain clearance imaging using 18F-MK6240 PET (positron emission tomography). CSF assessment includes Aβ42 (amyloid beta 42), t-tau (total tau) and p-tau181 (tau phosphorylated at threonine 181).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male and female subjects between 60-80 years old

• All subjects will speak English as their first language or demonstrate proficiency in English.

• All subjects will have normal cognition at baseline: a Clinical dementia rating CDR=0, Global deterioration Scale GDS <2

• For the HTN subjects: systolic HTN defined according to Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood pressure (JNC) 7 report. Specifically: Blood pressure in the ranges greater or equal to 140 mmHG, which is a mean of three seated BP readings on each of two or more office visits

Exclusion Criteria:

• Non-essential hypertension

• Diabetes

• Isolated diastolic hypertension

• Neurodegenerative disorders (i.e Parkinson disease)

• Dementia or Mild cognitive impairment at baseline

• Long life major depression. Baseline scores greater or equal to 20 on Beck Depression Inventory at baseline

• Long-life DSM-IV axis 1 disorders

• Mental retardation

• Substance abuse

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Hypertension
• Mild Cognitive Impairment
• Nerve Degeneration

Locations

Country	Name	City	State
United States	Weill Cornell Medicine	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cerebral blood flow	cerebral blood flow with arterial spin labeling MRI	Baseline and up to 24 month follow up
Primary	Change in Brain Clearance	the rate of radiotracer removal from the brain ventricle after injection of MK-6240 images, measured with positron emission tomography	Baseline and up to 24 month follow up
Primary	Change in total tau	total tau protein measured in cerebrospinal fluid	Baseline and up to 24 month follow up
Primary	Change in amyloid 42	amyloid 42 protein measured in cerebrospinal fluid	Baseline and up to 24 month follow up
Primary	Change in cognitive performance	A composite score of tests assessing: Immediate and delayed memory (score ranges in parentheses): Craft Story immediate (0-44) and delayed recall (0-44), Guild battery immediate (0-21) and delayed recall (0-21) of paragraph and word pairs immediate (0-10) and delayed (0-10).; Working memory: Number Span test forward (0-14) and backward (0-14); Naming: Verbal Naming Test (0-26).; Attention: Trail Making Test part A (0-25); Executive functions: Trail Making Test Part B (score range 0-13) and Wisconsin Sorting Card Test (0-128).; Verbal Fluency: Category Fluency: animals (0-30) and vegetables (0-30), category letters F (0-30) and L (0-30).; Each test is transformed into normative z-score. For each domain the scores are expressed as a composite z-score of all the tests assessing a given domain. The score range from -3.0 - to +3.0 higher indicating better performance.	Baseline and up to 24 month follow up