Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study)

NCT05331144 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STU-2021-12101R01AG076660-01
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if intensive lowering of systolic blood pressure (SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high risk for memory decline or dementia.

Conditions

Cognitively Normal Older Adults; Hypertension; Subjective Cognitive Decline; Family History of Dementia

Keywords

Dementia; Alzheimer's Disease; Cognitive Function; Blood Pressure; Amyloid; Tau

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ)

  Brain Aβ will be measured by annual change of amyloid mean cortical standardized uptake value ratio (SUVR) with positron emission tomography (PET).

  Baseline, 24 months

Secondary Outcomes (8)

• Change From Baseline in Brain Tau Deposition

  Baseline, 24 months

• Change From Baseline in regional Cerebral Blood Flow (CBF)

  Baseline, 12 months, 24 months

• Change From Baseline in global Cerebral Blood Flow (CBF)

  Baseline, 12 months, 24 months

• Change From Baseline in Arterial Stiffness

  Baseline, 12months, 4 months

• Change From Baseline in Amplitude of Low Frequency Fluctuations of Blood-Oxygen-Level-Dependent Signal (BOLD ALFF)

  Baseline, 12 months, 24 months

Study Arms (2)

Intensive Treatment (IT)

EXPERIMENTAL

Lowering SBP \< 120 mmHG

Drug: Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine)

Usual Care (UC)

ACTIVE COMPARATOR

Participants will follow their PCP's recommendations for BP control

Other: PCP

Interventions

Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine) DRUG

Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine) will be used to treat high blood pressure. Additional antihypertensive medications may be used if needed.

Intensive Treatment (IT)

PCP OTHER

Participants will follow their PCP's recommendations for BP control.

Usual Care (UC)

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60-85, all races/ethnicities, and both sexes are eligible;
• Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical judgment, may be rescreened in ≥ 7 days;
• Individuals with SBP ≥ 130 and SBP ≤ 180 if on 0 or 1 antihypertensive medications; ≥130 and ≤170 on up to 2 medications; ≥130 and ≤160 on up to 3 medications; ≥130 and ≤150 on up to 4 medications. Those on antihypertensives are eligible. If an individual, not treated for hypertension (HTN), has a SBP ≥ 125 mmHg, consider rescreening after 24 hours;
• Willingness to be randomized into the treatment groups and ability to return to clinic for follow-up visits over 24 months;
• Fluency in English or Spanish or both, adequate visual and auditory acuity to allow neuropsychological testing;
• Participants must have a regular healthcare provider.

You may not qualify if:

• Clinically documented history of stroke, focal neurological signs or other major cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence of infection, infarction, or other brain lesions;
• Diagnosis of AD or other type of dementia, or significant neurologic diseases such as Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head trauma or normal pressure hydrocephalus;
• Evidence of severe major depression (GDS ≥ 12, may be rescreened after 12 weeks or longer if evidence of reactive depression or temporary mood disturbances) or clinically significant psychopathology, (e.g., psychosis and schizophrenia); if hospitalized in past year, can be rescreened in 6 months; or presence of a major psychiatric disorder that in the investigator's opinion, could interfere with adherence to research assessments or procedures.
• Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest, cardiac bypass procedures within previous 6 months and congestive heart failure), or other severe medical conditions;
• History of atrial fibrillation and evidence on ECG with any of the following: active symptoms of persistent palpitation, dizziness, history of syncope, chest pain, dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea within the past 6 months; resting heart rate of \< 30 or \> 110 bpm; taking class I or III antiarrhythmic drugs including flecainide, propafenone, dronedarone, sotalol, dofetilide, and amiodarone; or clinical concerns for safely participating in lowering blood pressure.
• Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than 110 mmHg, may be rescreened in 1 week.
• Orthostatic hypotension, defined as the third standing SBP \< 100mmHg, may be rescreened after 2 weeks;
• History of significant autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis or polymyalgia rheumatica;
• Significant history of alcoholism or drug abuse within the last five years;
• Uncontrolled diabetes mellitus, defined as hemoglobin A1C \> 7.5%, or requiring insulin treatment;
• Regularly smoking cigarettes within the past year;
• Pacemaker or other medical device of metal that precludes performing MRI;
• Women with a potential for pregnancy, lactation/childbearing (2 year post-menopausal or surgically sterile to be considered not childbearing potential);
• Participant enrolled in another investigational drug or device study, either currently or within the past 2 months;
• Severe obesity with BMI \> 40 ; clinical judgment should be applied in all cases to assess patient safety and anticipated compliance;

Sponsors & Collaborators

• Rong Zhang: lead
• National Institute on Aging (NIA): collaborator
• Texas Health Resources: collaborator
• Michigan State University: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Hypertension; Dementia; Alzheimer Disease; Pick Disease of the Brain

Interventions

Angiotensin Receptor Antagonists; Losartan; Calcium Channel Blockers; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases; Frontotemporal Dementia; Frontotemporal Lobar Degeneration

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Cardiovascular Agents; Therapeutic Uses; Dihydropyridines; Pyridines

Study Officials

• Rong Zhang, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Wanpen Vongpatanasin, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• David Zhu, PhD

  Michigan State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tristyn Hall-Curtis, MBA

CONTACT

2143454245; TristynHall@texashealth.org

Study Design

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

Study Record Dates

• First Submitted: April 8, 2022
• First Posted: April 15, 2022
• Study Start: October 25, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At the time of publication of the primary results or within 9 months of the database lock whichever comes first.
• Access Criteria: The Study Steering Committee (SC) will review and approve the Data and Resource Sharing (DRS) requests from qualified investigators. A Material Transfer Agreement (MTA) and Data Use Agreement (DUA) will be in place with any academic group or scientists before any transfer of bio-samples or other data. Investigators receiving the data and/or samples will be required to abide by the conditions of these agreements. We will make the data and associated documentation available to other investigators only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate technology; and (3) a commitment to destroying or returning the data after analyses are completed.

Locations

US (1)