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

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ClinicalTrials.gov Identifier: NCT03354143
Recruitment Status : Recruiting
First Posted : November 27, 2017
Last Update Posted : February 7, 2020
Sponsor:
Collaborators:
Texas Health Resources
Michigan State University
Information provided by (Responsible Party):
Rong Zhang, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE November 15, 2017
First Posted Date  ICMJE November 27, 2017
Last Update Posted Date February 7, 2020
Actual Study Start Date  ICMJE April 10, 2018
Estimated Primary Completion Date May 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
Changes in intracranial pulsatility [ Time Frame: Baseline and 12-months ]
Changes in intracranial pulsatility will be measured with CINE phase-contrast MRI
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2017)
  • Cerebrospinal fluid Amyloid-β and tau [ Time Frame: Baseline and 12-months ]
  • Global and regional brain perfusion via Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline and 12-months ]
  • Regional brain volume via Magnetic Resonance Imaging (MRI) [ 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-Toolbox neurocognitive function [ Time Frame: Baseline, 6-months,12-months ]
  • NIH PROMIS patient-reported outcome measures of physical health [ Time Frame: Baseline, 6-months, 12-months ]
  • NIH PROMIS patient-reported outcome measures of mental health [ Time Frame: Baseline, 6-months, 12-months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
Official Title  ICMJE Hypertension, Intracranial Pulsatility and Brain Amyloid-beta Accumulation in Older Adults (HIPAC Trial)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Hypertension
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Standard Care
  • 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.
    Intervention: Drug: Intensive Treatment
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2017)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2022
Estimated Primary Completion Date May 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 79 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Wanpen Vongpatanasin, MD (214) 648-3180 Wanpen.Vongpatanasin@UTSouthwestern.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03354143
Other Study ID Numbers  ICMJE R01AG057571( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data will be shared approximately 18-24 months after the primary study publication.
Responsible Party Rong Zhang, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE
  • Texas Health Resources
  • Michigan State University
Investigators  ICMJE
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
PRS Account University of Texas Southwestern Medical Center
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP