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

NCT ID: NCT05331144

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-25
• Study Completion Date: 2027-12-31

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.

Detailed Description

The IPAT study is a 2-arm open-label randomized controlled trial to assess the effects of intensive pharmacological reduction of high blood pressure (SBP) on brain amyloid and tau protein deposition (Alzheimer's Disease pathology) in older adults who are at high risk for AD and related dementias, that is, those who have high blood pressure, family history of dementia, or subjective memory complaints. Furthermore, IPAT will examine effects of intensive blood pressure lowering on brain volume, perfusion, and neural network connectivity using magnetic resonance imaging (MRI) and cognitive performance.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Intensive Treatment (IT)

Lowering SBP \< 120 mmHG

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Usual Care (UC)

Participants will follow their PCP's recommendations for BP control

Group Type: ACTIVE_COMPARATOR

PCP

Intervention Type: OTHER

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

Interventions

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

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.

Intervention Type: DRUG

PCP

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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;
• Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix "-sartan"; allergy to amlodipine;
• Abnormal screening laboratory tests (e.g., liver ALT and AST > 3 x ULN, GFR < 30 or Hct < 28%); may be rescreened after 2 weeks or longer;
• A medical condition likely to limit survival to less than 3 years;
• Participant has any condition(s) judged by the study investigator to be medically inappropriate, risky or likely to cause poor study compliance. For example:

1. Plans to move outside the clinic catchment area in the next 2 years;

2. Significant concerns about participation in the study from spouse, significant other, or family members;

3. Lack of support from primary health care provider;

4. Residence too far from the study clinic site such that transportation is a barrier including persons who require transportation assistance provided by the study clinic funds for screening or randomization visits;

5. Residence in a nursing home; persons residing in an assisted living or retirement community are eligible if they meet the other criteria;

6. Other medical, psychiatric, or behavioral factors that, in the judgment of the site PI or clinician, may interfere with study participation or the ability to follow the study Protocol.

7. Couples or significant partners who live together cannot be enrolled or participate simultaneously in the study.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Texas Health Resources

OTHER

Sponsor Role: collaborator

Michigan State University

OTHER

Sponsor Role: collaborator

Rong Zhang

OTHER

Sponsor Role: lead

Responsible Party

Rong Zhang

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rong Zhang, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

Wanpen Vongpatanasin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center

David Zhu, PhD

Role: PRINCIPAL_INVESTIGATOR

Michigan State University

Locations

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Tristyn Hall-Curtis, MBA

Role: CONTACT

TristynHall@texashealth.org

2143454245

Facility Contacts

Tristyn Hall-Curtis, MBA

Role: primary

TristynHall@texashealth.org

214-345-4245

Other Identifiers

1R01AG076660-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU-2021-1210

Identifier Type: -

Identifier Source: org_study_id