HypertensionPhase 2HIPACNCT03354143
Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
A Phase 2 study testing Intensive Treatment in people with Hypertension, run by University of Texas Southwestern Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 55 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- Intensive Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2018to 30 Mar 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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;
- History of B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable);
- Any conditions judged by the study investigators to be either medically inappropriate, or risky for participant or likely to have poor study adherence;
- Claustrophobia;
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Standard Care, Intensive Treatment
- Keywords
- Dementia, Alzheimer's Disease, Blood Pressure, Cognitive Function, Magnetic Resonance Imaging
- Medical subject headings
- Hypertension, Dementia, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard CareOther
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 TreatmentOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline and 12-months
Secondary outcomes (8)
Changes in Overall Average 24 Hour Systolic Blood Pressure
changes in overall average 24 hr ambulatory systolic blood pressure will be assessed SpaceLabs monitor
Measured: Baseline and 12-months
Changes in Overall Average 24hr Diastolic Blood Pressure
changes in overall average 24 hr ambulatory diastolic blood pressure will be assessed SpaceLabs monitor
Measured: Baseline and 12-months
Regional Cortical Thickness Via Magnetic Resonance Imaging (MRI)
Measured: Baseline and 12-months
Brain White Matter Hyperintensity (WMH) Via Magnetic Resonance Imaging (MRI)
White matter hyperintensities (WMH) on brain T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance images (MRI) are commonly observed in older adults over 65 years old, and more extensive in those with vascular or Alzheimer's disease type of dementia. Qualitative and quantitative WMH characterization has been used as a biomarker to assist cerebral small vessel disease diagnosis and to assess treatment effects. In this report, the size of the WMH has been assessed with the PGS software, the top performer of the deep-learning algorithms from the 2017 MICCAI WMH segmentation challenge. The unit of the WMH total size presented in this report is in mL.
Measured: Baseline and 12-months
Brain White Matter Microstructural Integrity Via Magnetic Resonance Imaging (MRI)
Fractional Anisotropy (FA) values are a measure of how directed diffusion is in a tissue, typically ranging from 0 to 1. A value of 0 indicates isotropic diffusion (diffusion is the same in all directions), while a value of 1 indicates highly anisotropic diffusion (diffusion is restricted to a single direction). FA is often used in diffusion tensor imaging (DTI) and is thought to reflect fiber density, axonal diameter, and myelination in white matter.
Measured: Baseline and 12-months
Brain Neural Network Functional Connectivity Via Magnetic Resonance Imaging (MRI)
The brain's functional connectivity, particularly within the Default Mode Network (DMN), can be assessed using functional magnetic resonance imaging (fMRI) through the correlations between the activity of the brain regions within a network. In this report, the DMN regions were identified with a seed-based approach from another clinical trial with 420 subjects of a similar population. By identifying regions of interest (ROIs) within the DMN, researchers can analyze how these regions connect and interact with each other, revealing information about brain activity and potentially aiding in the diagnosis and understanding of various neurological and psychiatric conditions. Here, the functional connectivity of the DMN brain regions is reported in the unit of Pearson correlation R, with a range of 0 to 1 in this application. A high R value indicates a high level of connectivity.
Measured: Baseline and 12-months
NIH PROMIS Patient-reported Outcome Measures of Physical Health
PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Four items are used to assess global physical health. Three of these are administered using five-category response scales, and one item (rating of pain on average) uses a response scale of 0-10 that is recoded to five categories (0 = 1; 1-3 = 2; 4-6 = 3; 7-9 = 4; 10 = 5). T-score Metric: PROMIS measures use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. On the T-score metric:
A score of 40 is one SD lower than the mean of the reference population. A score of 60 is one SD higher than the mean of the reference population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function).A score of 60 is one standard deviation above the average population
Measured: Baseline and 12-months
NIH PROMIS Patient-reported Outcome Measures of Mental Health
PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Four items are used to assess global physical health. Three of these are administered using five-category response scales, and one item (rating of pain on average) uses a response scale of 0-10 that is recoded to five categories (0 = 1; 1-3 = 2; 4-6 = 3; 7-9 = 4; 10 = 5). T-score Metric: PROMIS measures use a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. On the T-score metric: A score of 40 is one SD lower than the mean of the reference population. A score of 60 is one SD higher than the mean of the reference population. For PROMIS measures, higher scores equals more of the concept being measured (e.g., more Fatigue, more Physical Function). A score of 60 is one standard deviation above the average population
Measured: Baseline and 12-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2017
- Study start10 Apr 2018
- Primary completion22 Jan 2024
- Study completion30 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Texas Health Resources, Michigan State University, National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Rong Zhang, University of Texas Southwestern Medical Center
- Investigators
- Rong Zhang, PhD, Principal investigator, University of Texas Southwestern Medical Center and Texas Health ResourcesWanpen Vongpatanasin, MD, Principal investigator, University of Texas Southwestern Medical CenterDavid Zhu, PhD, Principal investigator, Michigan State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03354143
- Sponsor's protocol ID
- STU 102017-029
- Other IDs
- 5R01AG057571-05
- Acronym
- HIPAC
- Status last verified
- Jun 2025
- First submitted
- 15 Nov 2017
- Last updated
- 2 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared approximately 18-24 months after the primary study publication.
Publications
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.
PubMed 31710528
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
- ClinicalTrials.gov ID
- NCT03354143
- Acronym / sponsor ID
- HIPAC / STU 102017-029
- Conditions
- Hypertension
- Keywords
- Dementia, Alzheimer's Disease, Blood Pressure, Cognitive Function, Magnetic Resonance Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- Texas Health Resources, Michigan State University, National Institute on Aging (NIA)
- Study start
- 10 Apr 2018 (actual)
- Primary completion
- 22 Jan 2024 (actual)
- Study completion
- 30 Mar 2024 (actual)
- First posted
- 27 Nov 2017 (actual)
- Results
- Posted 2 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Standard Care | Active comparator | Other: Standard CareSubjects 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. |
| Intensive Treatment | Experimental | Other: Intensive TreatmentSubjects 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. |
| 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. |
Who may qualify
- Ages
- 55 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (19 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard CareCalcium channel blocker (CCB, amlodipine), angiotensin II receptor blocker (ARB, losartan), and other antihypertensive drugs will be used to reduce 24-hour SBP ≤ 130 mmHg. | Other | Standard Care |
| Intensive TreatmentCalcium channel blocker (CCB, amlodipine), angiotensin II receptor blocker (ARB, losartan), and other antihypertensive drugs will be used to reduce 24-hour SBP ≤ 120 mmHg. | Other | Intensive Treatment |
Primary outcome
Changes in Gray Matter Intracranial Pulsatility
Time frame: Baseline and 12-months
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
8 secondary outcomes
Changes in Overall Average 24 Hour Systolic Blood Pressure
Time frame: Baseline and 12-months
Changes in Overall Average 24hr Diastolic Blood Pressure
Time frame: Baseline and 12-months
Regional Cortical Thickness Via Magnetic Resonance Imaging (MRI)
Time frame: Baseline and 12-months
Brain White Matter Hyperintensity (WMH) Via Magnetic Resonance Imaging (MRI)
Time frame: Baseline and 12-months
Brain White Matter Microstructural Integrity Via Magnetic Resonance Imaging (MRI)
Time frame: Baseline and 12-months
Brain Neural Network Functional Connectivity Via Magnetic Resonance Imaging (MRI)
Time frame: Baseline and 12-months
NIH PROMIS Patient-reported Outcome Measures of Physical Health
Time frame: Baseline and 12-months
NIH PROMIS Patient-reported Outcome Measures of Mental Health
Time frame: Baseline and 12-months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31710528Gottesman 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.
- Individual participant dataSharing planned: Yes. Data will be shared approximately 18-24 months after the primary study publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rong Zhang, PhD principal investigator
University of Texas Southwestern Medical Center and Texas Health Resources
Wanpen Vongpatanasin, MD principal investigator
University of Texas Southwestern Medical Center
David Zhu, PhD principal investigator
Michigan State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intensive Treatment in people with Hypertension, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Gray Matter Intracranial Pulsatility (time frame: Baseline and 12-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03354143, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2025.