Clinical trial NCT05331144: Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study)
Official title: Impact of Intensive Treatment of Systolic Blood Pressure on Brain Perfusion, Amyloid, and Tau in Older Adults (IPAT Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cognitively Normal Older Adults
Hypertension
Subjective Cognitive Decline
Family History of Dementia
Keywords: Dementia
Alzheimer's Disease
Cognitive Function
Blood Pressure
Amyloid
Tau
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Texas Health Resources
name: Michigan State University
First posted: 2022-04-15
Enrollment: 180
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ)
timeFrame: Baseline, 24 months
Secondary outcomes:
measure: Change From Baseline in Brain Tau Deposition
timeFrame: Baseline, 24 months
measure: Change From Baseline in regional Cerebral Blood Flow (CBF)
timeFrame: Baseline, 12 months, 24 months
measure: Change From Baseline in global Cerebral Blood Flow (CBF)
timeFrame: Baseline, 12 months, 24 months
measure: Change From Baseline in Arterial Stiffness
timeFrame: Baseline, 12months, 4 months
measure: Change From Baseline in Amplitude of Low Frequency Fluctuations of Blood-Oxygen-Level-Dependent Signal (BOLD ALFF)
timeFrame: Baseline, 12 months, 24 months
measure: Change From Baseline in White Matter Hyperintensity Volume
timeFrame: Baseline, 12 months, 24 months
measure: Change From Baseline in Brain Neural Network Connectivity
timeFrame: Baseline, 12 months, 24 months
measure: Change From Baseline in Neurocognitive Function
timeFrame: Baseline, 12 months, 24 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Rong Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Southwestern Medical Center
name: Wanpen Vongpatanasin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Michigan State University
name: David Zhu, PhD
role: PRINCIPAL_INVESTIGATOR
References: