To conduct a proof of concept study in patients with mild to moderate Alzheimer's Disease in order to determine if there is less global brain atrophy over one year, as measured by ventricular enlargement as a primary outcome measure, when patients are randomized to treatment with an angiotensin receptor blocker (ARB) compared to an angiotensin converting enzyme inhibitor (ACEI).
This study uses a simple validated measure of brain atrophy as a surrogate marker in a repurposing effort that could recast an antihypertensive medication as a cognitive enhancer/neuroprotective agent and possibly as a drug of choice for Alzheimer patients and patients at risk for AD. If the proof of concept result is positive, a larger study would be warranted with potential practice-changing impact.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)
Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)
University of Calgary
Calgary, Alberta, Canada
University of Lethbridge
Lethbridge, Alberta, Canada
UBC Hospital
Vancouver, British Columbia, Canada
Hamilton General Hospital
Ventricular enlargement
Change in ventricular size, on 3D T1 MR imaging, after 12 months of treatment
Time frame: 12 months
Safety - Blood pressure
Change in blood pressure (BP) measurements after 12 months of treatment.
Time frame: 12 months
Safety - Vital signs
Change in vital sign (heart rate, pulse) measurements after 12 months of treatment.
Time frame: 12 months
Safety - Electrolytes
Change in electrolyte measurements (Na, K) after 12 months of treatment.
Time frame: 12 months
Safety - Adverse Events
Adverse events and serious adverse events over 12 months of treatment.
Time frame: 12 months
Hippocampal volume
Change in hippocampal volume measurements after 12 months of treatment
Time frame: 12 months
Grey/White matter volume
Volume of grey and white matter in the cingulate, parietotemporal and dorsolateral frontal regions after 12 months of treatment
Time frame: 12 months
Cognitive and functional measures
Determine comparative efficacy of perindopril vs. telmisartan on cognitive and functional measures and on other structural brain imaging measures in this participant population
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Hamilton, Ontario, Canada
Parkwood Institute
London, Ontario, Canada
Centre for Memory and Aging
Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
St. Michael's Hospital
Toronto, Ontario, Canada
Baycrest Health Sciences
Toronto, Ontario, Canada
Centre for Addiction and Mental Health (CAMH)
Toronto, Ontario, Canada
Time frame: 6 and 12 months