To assess whether temporary discontinuation of antihypertensive therapy in mildly cognitively impaired older patients on antihypertensive treatment improves cognitive and psychological functioning.
ID
Source
Brief title
Condition
- Other condition
- Central nervous system vascular disorders
- Dementia and amnestic conditions
Synonym
Health condition
depressie, apathie, dagelijks functioneren en kwaliteit van leven
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is the change in the compound cognitive score between baseline
and follow-up at 4 months after randomisation.
Secondary outcome
Secondary outcomes are the changes in the four separate cognitive domains
(executive functioning, cognitive speed, immediate memory, and delayed memory);
depressive symptoms, apathy, daily functioning, and quality of life between
baseline and follow-up, 4 months after randomisation; and change in cerebral
perfusion at MRI scan.
Background summary
A high blood pressure at middle age is deleterious and may lead to
cardiovascular disease, dementia and depression and apathy at old age.
Therefore, many people use antihypertensives. However, the usefulness of
antihypertensive treatment at old age had not been convincingly demonstrated
and increasing evidence suggests that at old age a low blood pressure is
deleterious for mental health. Low blood pressure at old age may compromise
cerebral perfusion, which may increase the risk of cognitive impairment,
depressive symptoms, and apathy. Cerebral imaging studies have shown that
cerebral blood flow is reduced in areas of small vessel disease and that the
degree of hypoperfusion correlates with disease severity. Hence, blood pressure
reduction in older people may lead to hypoperfusion, especially in patients
with cerebral small vessel disease, resulting in increased mental health
problems like cognitive impairment, depression, and apathy.
Study objective
To assess whether temporary discontinuation of antihypertensive therapy in
mildly cognitively impaired older patients on antihypertensive treatment
improves cognitive and psychological functioning.
Study design
Randomized non-blinded controlled clinical trial.
Intervention
Patients will be randomized to either continuation (n=200) or discontinuation
(n=200) of antihypertensive treatment. Discontinuation of antihypertensive
medication by patients* own general practitioner may vary from abrupt and
complete discontinuation to gradual and partial discontinuation, with a 20
mmgHg increase in systolic blood pressure as target and 180 mmHg as maximum
systolic blood pressure. For the various antihypertensive drugs commonly used
by older people a discontinuation algorithm will be used. Discontinuation will
be executed and completed within four weeks from randomization by the GP for a
period of three months thereafter.
Study burden and risks
Patients have to come to the LUMC for a MRI-scan. Assessments of cognitive
functioning and mental wellbeing (2x2 hours) will be done at the patients*
home. The patients will receive blood pressure measurements every 2 weeks
during the first 4 weeks by their GP. Thereafter, in order to make both
treatment arms as similar as possible the blood pressure of all patients, both
in the discontinuation arm and the stop arm, will be monitored monthly during
the entire study period by the research personnel and patients in the
discontinuation arm will be put on their original antihypertensive medication
when systolic blood pressure exceeds 200 mmHg or diastolic blood pressure
exceeds 110 mmHg. Moreover, all cardiovascular events during the study will be
closely monitored to prevent an increase in cardiovascular events in the
discontinuation group. A Data Safety and Monitoring Board (DSMB) will be
installed for monitoring of the safety data (cardio- and cerebrovascular
events). The DSMB will check progression of the study and adverse events after
the first 50 participants, and afterwards after every 100 participants. A
charter has been written detailing the exact procedures.
Postbus 9600
2300 RC Leiden
NL
Postbus 9600
2300 RC Leiden
NL
Listed location countries
Age
Inclusion criteria
(1) age >= 75 years,
(2) current antihypertensive treatment with a calcium antagonist, beta-blocker, diuretic, ACE-inhibitor, or angiotensin-II-receptor blocker prescribed by their general practitioner for hypertension,
(3) a last systolic blood pressure as reported in the chart of the general practitioner <= 160 mmHg(4) Mini-Mental State Examination (MMSE) score 21t/m 27.
Exclusion criteria
A history of myocardial infarction and/or coronary reperfusion procedures (CABG/PCI) < 3 years, stroke, or heart failure requiring antihypertensive medication and/or a clinical diagnosis of dementia.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL34418.058.10 |