Cerebrovascular Disease, Hypertension, Systolic
Conditions
Keywords
Hypertension, systolic, Elderly (> or equal to 75 years), Cerebrovascular disease
Brief summary
This randomized clinical trial examines if lowering and maintaining 24-hour ambulatory systolic blood pressure to \<130 mmHg (intensive control) versus \<145 mmHg (standard control) slows/halts the progression of deterioration of mobility and cognitive function linked to white-matter disease (also known as white-matter hyperintensity or WMH) in patients with normal or mildly impaired mobility and cognition in subjects with detectable cerebrovascular disease (\>0.5% WMH fraction of intracranial contents). The study patients will be enrolled and randomized to one of two levels of ambulatory blood pressure control (intensive to achieve a goal 24-hour systolic blood pressure of \< 130 mmHg or standard to achieve a goal 24-hour systolic blood pressure of \< 145 mmHg) for a total of 36 months.
Detailed description
The study patients will be enrolled and randomized to one of two levels of ambulatory BP control (intensive to achieve a goal 24-hour systolic BP of \< 130 mmHg or standard to achieve a goal 24-hour systolic BP of \< 145 mmHg) for a total of 36 months. Similar antihypertensive regimens will be used in both of the treatment groups. Titration of antihypertensive therapies will be performed at monthly intervals for the first 3 to 6 months post-randomization to achieve goal systolic BP. The primary and secondary outcomes will be evaluated at baseline, and following 18 months and 36 months of therapy.
Interventions
OTHERAnti-hypertensive therapy to SBP 130 mm Hg
Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 130 mm Hg
OTHERAnti-hypertensive therapy to SBP 145 mm Hg
Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 145 mm Hg
Sponsors
National Institute on Aging (NIA)
UConn Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 75 years of age or older * Seated clinic systolic BP \>150 mmHg in the untreated state (see criterion D) * At risk for cerebrovascular disease (history of smoking, dyslipidemia, type 2 diabetes, longstanding hypertension, family history). Patients must have visible (0.5% WMH or more)white-matter hypertensity lesions on screening magnetic resonance imaging * To achieve success in maintaining a 24-hour systolic BP of \<140-145 mmHg in the standard treatment group or a systolic BP \<125-130 mmHg in the intensive treatment group, patients will be eligible for inclusion if (1) their clinic systolic BP is 150-170 mmHg, and they are taking 0 to 2 antihypertensives, (2) their systolic BP is \>170 mmHg and they are taking 0 to 1 antihypertensives
Exclusion criteria
* Uncontrolled diabetes mellitus (HBA1c \>10%) * History of stroke, dementia or clinically impaired gait (Mini-mental status exam score (MMSE) \<24, Short Physical Performance Battery for gait (SPPB) \< 9,) * Body Mass Index \> 45 kg/m2 and/or arm circumference \> 44 cm) * Poor kidney function (defined as estimated GFR \<30 ml/minute) * Active liver disease or serum transaminases \>3 times the upper limit of normal * Major cardiovascular event (e.g. myocardial infarction) or procedure (e.g. cardiac bypass surgery) in past 3 months; stroke with residual gait abnormality * Uncompensated congestive heart failure (NYHA class III or IV or documented ejection fraction \<30%) * Chronic atrial fibrillation that disallows ambulatory BP monitoring to be successfully performed * Medical conditions that limit survival to \< 3 years * Non-dermatologic cancer diagnosed within 2 years * Organ transplantation requiring anti-rejection drug therapy * Severe and unexplained weight loss (\>15%) in past 6 months * Medical need to undergo recurrent phlebotomy or blood transfusions * Current participation in another investigational trial * Unable to obtain informed consent * Factors limiting adherence to the interventions * MRI contraindications (including MRI-incompatible implants, severe claustrophobia).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mobility - Measured by Change in Gait Speed | Change from baseline to 36 months | Change in gait speed (walking 8 meters) in seconds mediated by the accrual of white-matter hyperintensity lesions (WMH/intracranial cavity volume) using MRI and including degeneration of axonal and myelin components of white matter using MRI technology known as diffusion tensor imaging (DTI). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function - as Measured by Change in Stroop Test Score | Change from baseline to 36 months | Change in cognitive function as measured by stroop test score: number of correct responses in 45 seconds. The score for the Stroop Test is the number of correct responses provided in 45 seconds on each test condition: word reading, color naming, and inhibition. For the inhibition condition, words are written in an incongruous ink color (e.g., the word red written in blue ink) and participants must provide the ink color. Scores range from 0 to no upper limit, with higher scores indicating better performance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intensive Intensive anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 130 mmHg
Anti-hypertensive therapy to SBP 130 mm Hg: Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 130 mm Hg | 99 |
| Standard Standard anti-hypertensive therapies using standard blood pressure medications to lower blood pressure to a level less than or equal to 145 mmHg
Anti-hypertensive therapy to SBP 145 mm Hg: Anti-hypertensive therapy to achieve 24 hour systolic blood pressure less than or equal to 145 mm Hg | 100 |
| Total | 199 |
Baseline characteristics
| Characteristic | Intensive | Standard | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 99 Participants | 100 Participants | 199 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 85 Participants | 89 Participants | 174 Participants |
| Sex: Female, Male Female | 57 Participants | 51 Participants | 108 Participants |
| Sex: Female, Male Male | 42 Participants | 49 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 99 | 4 / 100 |
| other Total, other adverse events | 86 / 99 | 70 / 100 |
| serious Total, serious adverse events | 33 / 99 | 36 / 100 |
Outcome results
Primary
Mobility - Measured by Change in Gait Speed
Change in gait speed (walking 8 meters) in seconds mediated by the accrual of white-matter hyperintensity lesions (WMH/intracranial cavity volume) using MRI and including degeneration of axonal and myelin components of white matter using MRI technology known as diffusion tensor imaging (DTI).
Time frame: Change from baseline to 36 months
Population: 78 participants from the intensive group and 86 participants from the standard group were included in the mobility analysis because 1 participant from the intensive group did not complete mobility testing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intensive | Mobility - Measured by Change in Gait Speed | 0.4 seconds | Standard Deviation 2 |
| Standard | Mobility - Measured by Change in Gait Speed | 0.42 seconds | Standard Deviation 2.73 |
Secondary
Cognitive Function - as Measured by Change in Stroop Test Score
Change in cognitive function as measured by stroop test score: number of correct responses in 45 seconds. The score for the Stroop Test is the number of correct responses provided in 45 seconds on each test condition: word reading, color naming, and inhibition. For the inhibition condition, words are written in an incongruous ink color (e.g., the word red written in blue ink) and participants must provide the ink color. Scores range from 0 to no upper limit, with higher scores indicating better performance.
Time frame: Change from baseline to 36 months
Population: 69 participants from the intensive group and 76 participants from the standard group were included in analysis because 10 participants in the intensive group and 10 participants in the standard group did not complete cognitive testing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intensive | Cognitive Function - as Measured by Change in Stroop Test Score | -2.7 correct responses | Standard Deviation 8 |
| Standard | Cognitive Function - as Measured by Change in Stroop Test Score | -0.8 correct responses | Standard Deviation 6.4 |