Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial) (HIPAC)
Primary Purpose
Hypertension
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Standard Care
Intensive Treatment
Sponsored by
About this trial
This is an interventional prevention trial for Hypertension focused on measuring Dementia, Alzheimer's Disease, Blood Pressure, Cognitive Function, Magnetic Resonance Imaging
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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;
- 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
Sites / Locations
- UT Southwestern Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Standard Care
Intensive Treatment
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Changes in intracranial pulsatility
Changes in intracranial pulsatility will be measured with CINE phase-contrast MRI
Secondary Outcome Measures
Cerebrospinal fluid Amyloid-β and tau
Global and regional brain perfusion via Magnetic Resonance Imaging (MRI)
Regional brain volume via Magnetic Resonance Imaging (MRI)
Regional cortical thickness via Magnetic Resonance Imaging (MRI)
Brain white matter hyperintensity (WMH) via Magnetic Resonance Imaging (MRI)
Brain white matter microstructural integrity via Magnetic Resonance Imaging (MRI)
Brain neural network functional connectivity via Magnetic Resonance Imaging (MRI)
NIH-Toolbox neurocognitive function
NIH PROMIS patient-reported outcome measures of physical health
NIH PROMIS patient-reported outcome measures of mental health
Full Information
NCT ID
NCT03354143
First Posted
November 15, 2017
Last Updated
August 18, 2023
Sponsor
University of Texas Southwestern Medical Center
Collaborators
Texas Health Resources, Michigan State University
1. Study Identification
Unique Protocol Identification Number
NCT03354143
Brief Title
Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
Acronym
HIPAC
Official Title
Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
February 28, 2024 (Anticipated)
Study Completion Date
March 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
Texas Health Resources, Michigan State University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension
Keywords
Dementia, Alzheimer's Disease, Blood Pressure, Cognitive Function, Magnetic Resonance Imaging
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Care
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Intensive Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Standard Care
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Intensive Treatment
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in intracranial pulsatility
Description
Changes in intracranial pulsatility will be measured with CINE phase-contrast MRI
Time Frame
Baseline and 12-months
Secondary Outcome Measure Information:
Title
Cerebrospinal fluid Amyloid-β and tau
Time Frame
Baseline and 12-months
Title
Global and regional brain perfusion via Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and 12-months
Title
Regional brain volume via Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and 12-months
Title
Regional cortical thickness via Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and 12-months
Title
Brain white matter hyperintensity (WMH) via Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and 12-months
Title
Brain white matter microstructural integrity via Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and 12-months
Title
Brain neural network functional connectivity via Magnetic Resonance Imaging (MRI)
Time Frame
Baseline and 12-months
Title
NIH-Toolbox neurocognitive function
Time Frame
Baseline, 6-months,12-months
Title
NIH PROMIS patient-reported outcome measures of physical health
Time Frame
Baseline, 6-months, 12-months
Title
NIH PROMIS patient-reported outcome measures of mental health
Time Frame
Baseline, 6-months, 12-months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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;
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rong Zhang, PhD
Organizational Affiliation
University of Texas Southwestern Medical Center and Texas Health Resources
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wanpen Vongpatanasin, MD
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Zhu, PhD
Organizational Affiliation
Michigan State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be shared approximately 18-24 months after the primary study publication.
Citations:
PubMed Identifier
31710528
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.
Results Reference
derived
Learn more about this trial
Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
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