Intensive blood pressure treatment's effect on Alzheimer's disease in older adults

Impact of Intensive Treatment of Systolic Blood Pressure on Brain Perfusion, Amyloid, and Tau in Older Adults (IPAT Study)

This study is testing if lowering blood pressure more aggressively can help older adults at risk for Alzheimer's disease by reducing harmful brain changes related to the condition.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 60 Years to 85 Years
• Sex: All
• Sponsor: University of Texas Southwestern Medical Center (Academic / other)
• Locations: 1 site (Dallas, Texas)
• Trial ID: NCT05331144 on ClinicalTrials.gov

What this trial studies

The IPAT study is a Phase 2 interventional trial that investigates whether intensive lowering of systolic blood pressure (SBP) can reduce Alzheimer's disease-related brain pathology, specifically amyloid and tau protein deposition, in older adults at high risk for cognitive decline. Participants aged 60-85 with high blood pressure, a family history of dementia, or subjective memory complaints will be randomized to receive antihypertensive medications, including Angiotensin II Receptor Blockers and Calcium Channel Blockers. The study will also assess changes in brain volume, perfusion, and neural connectivity using MRI, alongside cognitive performance evaluations over a 24-month period.

Who should consider this trial

Good fit: Ideal candidates are cognitively normal older adults aged 60-85 with high blood pressure and a family history of dementia or subjective cognitive decline.

Not a fit: Patients with a clinically documented history of stroke or major cerebrovascular diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new strategies for preventing or delaying Alzheimer's disease in at-risk older adults.

How similar studies have performed: Other studies have shown promising results in managing blood pressure to potentially impact cognitive decline, but this specific approach is novel.

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.

Where this trial is running

Dallas, Texas

• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Rong Zhang, PhD — University of Texas Southwestern Medical Center
• Study coordinator: Tristyn Hall-Curtis, MBA

Conditions Cognitively Normal Older Adults; Hypertension; Subjective Cognitive Decline; Family History of Dementia; Dementia; Alzheimer's Disease; Cognitive Function; Blood Pressure