Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, Perindopril, Telmisartan, Brain atrophy
Brief summary
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).
Detailed description
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.
Interventions
DRUGPerindopril
Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)
DRUGTelmisartan
Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)
Sponsors
Alzheimer's Drug Discovery Foundation
Weston Brain Institute
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Probable AD dementia or Possible AD dementia due to concomitant cerebrovascular disease (as permitted by the study
Exclusion criteria
), using the 2011 McKhann criteria. 2. Previous brain MRI or CT scan to rule out exclusionary pathology, and absence of stepwise decline since the previous scan. 3. Age 50 years or older 4. Standardized Mini Mental State Examination (SMMSE) score of 16-27 at screening visit 5. Sufficient hearing and vision to participate in testing as per investigator's judgement 6. Sufficient fluency in English to understand instructions and to be able to complete SMMSE 7. A study partner who in the opinion of the study investigator has regular interaction with the participant, can be present for study visits, can provide a collateral history and can ensure compliance with study procedures 8. HbA1C \<8.5%. Patients with stable type II diabetes are eligible for the study if there have been no severe hypoglycemic events requiring third party intervention (e.g. emergency department visit) for 6 months prior to randomization 9. Patients on cholinesterase inhibitors or memantine, medications for vascular risk factors (e.g., hypertension, cholesterol, diabetes), or on psychotropic medications must be on a stable dose for 30 days prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Adverse Events | 12 months | Adverse events and serious adverse events over 12 months of treatment. |
| Ventricular enlargement | 12 months | Change in ventricular size, on 3D T1 MR imaging, after 12 months of treatment |
| Safety - Electrolytes | 12 months | Change in electrolyte measurements (Na, K) after 12 months of treatment. |
| Safety - Vital signs | 12 months | Change in vital sign (heart rate, pulse) measurements after 12 months of treatment. |
| Safety - Blood pressure | 12 months | Change in blood pressure (BP) measurements after 12 months of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grey/White matter volume | 12 months | Volume of grey and white matter in the cingulate, parietotemporal and dorsolateral frontal regions after 12 months of treatment |
| Hippocampal volume | 12 months | Change in hippocampal volume measurements after 12 months of treatment |
| Cognitive and functional measures | 6 and 12 months | Determine comparative efficacy of perindopril vs. telmisartan on cognitive and functional measures and on other structural brain imaging measures in this participant population |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life - Caregiver burden | 12 months | Assess the comparative response of caregiver burden after treatment using Zarit burden interview. |
| Treatment responsiveness of resting state functional MRI (rsfMRI) | 12 months | Assess the comparative treatment responsiveness of multi-modal MRI, resting-state functional MRI (rsfMRI) and arterial spin labeling (in a subset of participants) and obtain pilot data. |
| Treatment responsiveness of Diffusion Tensor Imaging (DTI) | 12 months | Assess the comparative treatment responsiveness of Diffusion Tensor Imaging (DTI) and obtain pilot data |
| Neuropsychiatric Measures | 6 & 12 months | Assess the comparative treatment responsiveness of neuropsychiatric measures and obtain pilot data |
| Quality of Life - Health-related | 12 months | Assess health related quality of life after treatment using EQ-5D-5L questionnaire. |
Countries
Canada
Outcome results
None listed