Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)

Hypertension Clinical Trial

— HIPAC  

Official title:

Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03354143
• Other study ID #: R01AG057571
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 10, 2018
• Est. completion date: March 30, 2024

Study information

• Verified date: August 2023
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: March 30, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Intracranial Hypertension

Intervention

Drug:
• Standard Care
Calcium channel blocker (CCB, amlodipine), angiotensin II receptor blocker (ARB, losartan), and other antihypertensive drugs will be used to reduce 24-hour SBP = 130 mmHg.
• Intensive Treatment
Calcium channel blocker (CCB, amlodipine), angiotensin II receptor blocker (ARB, losartan), and other antihypertensive drugs will be used to reduce 24-hour SBP = 120 mmHg.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (3)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Michigan State University, Texas Health Resources

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in intracranial pulsatility	Changes in intracranial pulsatility will be measured with CINE phase-contrast MRI	Baseline and 12-months
Secondary	Cerebrospinal fluid Amyloid-ß and tau		Baseline and 12-months
Secondary	Global and regional brain perfusion via Magnetic Resonance Imaging (MRI)		Baseline and 12-months
Secondary	Regional brain volume via Magnetic Resonance Imaging (MRI)		Baseline and 12-months
Secondary	Regional cortical thickness via Magnetic Resonance Imaging (MRI)		Baseline and 12-months
Secondary	Brain white matter hyperintensity (WMH) via Magnetic Resonance Imaging (MRI)		Baseline and 12-months
Secondary	Brain white matter microstructural integrity via Magnetic Resonance Imaging (MRI)		Baseline and 12-months
Secondary	Brain neural network functional connectivity via Magnetic Resonance Imaging (MRI)		Baseline and 12-months
Secondary	NIH-Toolbox neurocognitive function		Baseline, 6-months,12-months
Secondary	NIH PROMIS patient-reported outcome measures of physical health		Baseline, 6-months, 12-months
Secondary	NIH PROMIS patient-reported outcome measures of mental health		Baseline, 6-months, 12-months