Clinical trial NCT03354143: Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
Official title: Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Dementia
Alzheimer's Disease
Blood Pressure
Cognitive Function
Magnetic Resonance Imaging
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Texas Health Resources
name: Michigan State University
First posted: 2017-11-27
Enrollment: 85
Sex: ALL
Minimum age (years): 55
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to determine if lowering blood pressure using FDA approved medication (antihypertensive drugs) alters brain pulsatility and reduces brain amyloid beta protein accumulation in older adults. Amyloid beta protein is high in the brain of older adults with Alzheimer's disease. Hypertension may increase brain amyloid beta protein accumulation and affect memory and thinking ability in older adults. However, whether lowering blood pressure reduces brain amyloid beta protein and improves brain function is inconclusive.

The investigators hypothesize that treating high blood pressure alters brain pulsatility, which in turn reduces brain amyloid beta protein accumulation and improves brain structure and function.


Eligibility criteria: Inclusion Criteria:

1. Age 55-79, all races/ethnicities, and both women and men are eligible;
2. Mini-mental state exam (MMSE) \> 26 to exclude cognitive impairment or dementia;
3. Healthy normotensive subjects (24-hour ambulatory BP\<125/75 mmHg without use of antihypertensive medication);
4. Patients with hypertension defined as 24-hour SBP ≥130 mmHg , patients on BP medications are eligible;
5. Patients with hypertension are willing to be randomized into either treatment group and ability to return to clinic or laboratory for follow-up visits over 12 months;
6. Fluency in English, adequate visual and auditory acuity to allow neuropsychological testing;
7. Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

Exclusion Criteria:

1. History of stroke, transient ischemic attack, traumatic brain injury or severe cerebrovascular disease by clinical diagnosis or past MRI/CT;
2. Diagnosis of AD or other type of dementia and neurodegenerative diseases;
3. Evidence of severe depression or other DSM-V Axis I psychopathology
4. Unstable heart disease based on clinical judgment (heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), evidence of atrial fibrillation on ECG, or other severe medical conditions;
5. Chronic kidney diseases with GFR \< 40 ml/min;
6. Orthostatic hypotension, defined as standing SBP\<100 mmHg;
7. History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis and polymyalgia rheumatica;
8. History of drug or alcohol abuse within the last 2 years;
9. Diagnosis of uncontrolled diabetes mellitus (fasting blood sugar ≥126 mg/dL or A1C \>7.5%)
10. Obstructive sleep apnea;
11. Regularly smoking cigarette within the past year;
12. Severe obesity with BMI ≥ 45;
13. Participants enrolled in another investigational drug or device study within the past 2 months;
14. Carotid stent or sever stenosis (\> 50%);
15. Pacemaker or other medical device of metal that precludes performing MRI;
16. History of B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable);
17. Any conditions judged by the study investigators to be either medically inappropriate, or risky for participant or likely to have poor study adherence;
18. Claustrophobia;
19. Pregnancy

Primary outcomes:
measure: Changes in intracranial pulsatility
timeFrame: Baseline and 12-months
Secondary outcomes:
measure: Cerebrospinal fluid Amyloid-β and tau
timeFrame: Baseline and 12-months
measure: Global and regional brain perfusion via Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12-months
measure: Regional brain volume via Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12-months
measure: Regional cortical thickness via Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12-months
measure: Brain white matter hyperintensity (WMH) via Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12-months
measure: Brain white matter microstructural integrity via Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12-months
measure: Brain neural network functional connectivity via Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12-months
measure: NIH-Toolbox neurocognitive function
timeFrame: Baseline, 6-months,12-months
measure: NIH PROMIS patient-reported outcome measures of physical health
timeFrame: Baseline, 6-months, 12-months
measure: NIH PROMIS patient-reported outcome measures of mental health
timeFrame: Baseline, 6-months, 12-months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center and Texas Health Resources
name: Rong Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Southwestern Medical Center
name: Wanpen Vongpatanasin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Michigan State University
name: David Zhu, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gottesman RF. To INFINITY and Beyond: What Have We Learned and What Is Still Unknown About Blood Pressure Lowering and Cognition? Circulation. 2019 Nov 12;140(20):1636-1638. doi: 10.1161/CIRCULATIONAHA.119.042827. Epub 2019 Nov 11. No abstract available.