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

NCT03354143 | Completed Phase 2 Results DMC

• 2 other identifiers: STU 102017-0295R01AG057571-05
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension

Keywords

Dementia; Alzheimer's Disease; Blood Pressure; Cognitive Function; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• Changes in Gray Matter Intracranial Pulsatility

  Changes (12 month timepoint minus baseline) in intracranial pulsatility will be measured with CINE phase-contrast MRI. We will use the velocity-encoded CINE PC MRI to measure intracranial pulsatility. Pulsatility measured in mm per cardiac cycle

  Baseline and 12-months

Secondary Outcomes (8)

• Changes in Overall Average 24 Hour Systolic Blood Pressure

  Baseline and 12-months

• Changes in Overall Average 24hr Diastolic Blood Pressure

  Baseline and 12-months

• Regional Cortical Thickness Via Magnetic Resonance Imaging (MRI)

  Baseline and 12-months

• Brain White Matter Hyperintensity (WMH) Via Magnetic Resonance Imaging (MRI)

  Baseline and 12-months

• Brain White Matter Microstructural Integrity Via Magnetic Resonance Imaging (MRI)

  Baseline and 12-months

Study Arms (3)

Standard Care

ACTIVE COMPARATOR

Subjects in the standard care arm will receive calcium channel blocker (CCB, amlodipine), angiotensin II receptor blocker (ARB, losartan), and other antihypertensive drugs to reduce 24-hour SBP ≤ 130 mmHg. Drug doses will be titrated to reach the BP target.

Other: Standard Care

Intensive Treatment

EXPERIMENTAL

Subjects in the intensive treatment arm will receive calcium channel blocker (CCB, amlodipine), angiotensin II receptor blocker (ARB, losartan), and other antihypertensive drugs to reduce 24-hour SBP ≤ 120 mmHg.

Other: Intensive Treatment

Control group subjects

NO INTERVENTION

Healthy normotensive subjects (24-hour ambulatory BP\<125/75 mmHg without use of antihypertensive medication) who undergo MRI as part of standard of care.

Interventions

Standard Care OTHER

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.

Standard Care

Intensive Treatment OTHER

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.

Intensive Treatment

Eligibility Criteria

• Age: 55 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-79, all races/ethnicities, and both women and men are eligible;
• Mini-mental state exam (MMSE) \> 26 to exclude cognitive impairment or dementia;
• Healthy normotensive subjects (24-hour ambulatory BP\<125/75 mmHg without use of antihypertensive medication);
• Patients with hypertension defined as 24-hour SBP ≥130 mmHg , patients on BP medications are eligible;
• 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;
• Fluency in English, adequate visual and auditory acuity to allow neuropsychological testing;
• Screening laboratory tests and ECG without significant abnormalities that might interfere with the study

You may not qualify if:

• History of stroke, transient ischemic attack, traumatic brain injury or severe cerebrovascular disease by clinical diagnosis or past MRI/CT;
• Diagnosis of AD or other type of dementia and neurodegenerative diseases;
• Evidence of severe depression or other DSM-V Axis I psychopathology
• 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;
• Chronic kidney diseases with GFR \< 40 ml/min;
• Orthostatic hypotension, defined as standing SBP\<100 mmHg;
• History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis and polymyalgia rheumatica;
• History of drug or alcohol abuse within the last 2 years;
• Diagnosis of uncontrolled diabetes mellitus (fasting blood sugar ≥126 mg/dL or A1C \>7.5%)
• Obstructive sleep apnea;
• Regularly smoking cigarette within the past year;
• Severe obesity with BMI ≥ 45;
• Participants enrolled in another investigational drug or device study within the past 2 months;
• Carotid stent or sever stenosis (\> 50%);
• Pacemaker or other medical device of metal that precludes performing MRI;

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Texas Health Resources: collaborator
• Michigan State University: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• 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.

  PMID: 31710528 DERIVED

MeSH Terms

Conditions

Hypertension; Dementia; Alzheimer Disease

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Dr. Rong Zhang
• Organization: IEEM

rongzhang@texashealth.org

214-345-4245

Study Officials

• Rong Zhang, PhD

  University of Texas Southwestern Medical Center and Texas Health Resources

  PRINCIPAL INVESTIGATOR

• Wanpen Vongpatanasin, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• David Zhu, PhD

  Michigan State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 27, 2017
• Study Start: April 10, 2018
• Primary Completion: January 22, 2024
• Study Completion: March 30, 2024
• Last Updated: July 2, 2025
• Results First Posted: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)