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

Sponsor
University of Texas Southwestern Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03354143
Collaborator
Texas Health Resources (Other), Michigan State University (Other)
120
Enrollment
1
Location
2
Arms
65.7
Anticipated Duration (Months)
1.8
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Standard Care
  • Drug: Intensive Treatment
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
Actual Study Start Date :
Apr 10, 2018
Anticipated Primary Completion Date :
Jul 31, 2023
Anticipated Study Completion Date :
Sep 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Standard Care

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.

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.
Experimental: Intensive Treatment

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.

Drug: 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.

Outcome Measures

Primary Outcome Measures

  1. Changes in intracranial pulsatility [Baseline and 12-months]

    Changes in intracranial pulsatility will be measured with CINE phase-contrast MRI

Secondary Outcome Measures

  1. Cerebrospinal fluid Amyloid-β and tau [Baseline and 12-months]

  2. Global and regional brain perfusion via Magnetic Resonance Imaging (MRI) [Baseline and 12-months]

  3. Regional brain volume via Magnetic Resonance Imaging (MRI) [Baseline and 12-months]

  4. Regional cortical thickness via Magnetic Resonance Imaging (MRI) [Baseline and 12-months]

  5. Brain white matter hyperintensity (WMH) via Magnetic Resonance Imaging (MRI) [Baseline and 12-months]

  6. Brain white matter microstructural integrity via Magnetic Resonance Imaging (MRI) [Baseline and 12-months]

  7. Brain neural network functional connectivity via Magnetic Resonance Imaging (MRI) [Baseline and 12-months]

  8. NIH-Toolbox neurocognitive function [Baseline, 6-months,12-months]

  9. NIH PROMIS patient-reported outcome measures of physical health [Baseline, 6-months, 12-months]

  10. NIH PROMIS patient-reported outcome measures of mental health [Baseline, 6-months, 12-months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
55 Years to 79 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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%)

  1. Obstructive sleep apnea;

  2. Regularly smoking cigarette within the past year;

  3. Severe obesity with BMI ≥ 45;

  4. Participants enrolled in another investigational drug or device study within the past 2 months;

  5. Carotid stent or sever stenosis (> 50%);

  6. Pacemaker or other medical device of metal that precludes performing MRI;

  7. History of B12 deficiency or hypothyroidism (stable treatment for at least 3 months is allowable);

  8. Any conditions judged by the study investigators to be either medically inappropriate, or risky for participant or likely to have poor study adherence;

  9. Claustrophobia;

  10. Pregnancy

Contacts and Locations

Locations

Site City State Country Postal Code
1 UT Southwestern Medical Center Dallas Texas United States 75390

Sponsors and Collaborators

  • University of Texas Southwestern Medical Center
  • Texas Health Resources
  • Michigan State University

Investigators

  • Principal Investigator: 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Rong Zhang, Professor of Neurology, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT03354143
Other Study ID Numbers:
  • R01AG057571
First Posted:
Nov 27, 2017
Last Update Posted:
Aug 15, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Rong Zhang, Professor of Neurology, University of Texas Southwestern Medical Center
Dementia
Alzheimer's Disease
Blood Pressure
Cognitive Function
Magnetic Resonance Imaging
Additional relevant MeSH terms:
Intracranial Hypertension
Hypertension

Study Results

No Results Posted as of Aug 15, 2022