Telmisartan vs. Perindopril in Mild-Moderate Alzheimer's Disease Patients

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dr. Sandra E Black; Sunnybrook Health Sciences Centre
• Collaborators: Alzheimer's Drug Discovery Foundation; Alzheimer’s Drug Discovery Foundation; Weston Brain Institute
• Treatments: Perindopril; Telmisartan

Criteria

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. At least 8 years of education

8. 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

9. 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

10. 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.

Exclusion criteria

1. Intolerance, or any contraindications, to study medications

2. Average SBP <110mmHg or average DBP <60 mmHg during screening

3. Familial autosomal dominant form of Alzheimer's disease

4. Creatinine clearance less than or equal to 30ml/min

5. Serum potassium > 5.5 mEq/L

6. ALT 3x > the upper limit of normal (ULN)

7. History of angioedema

8. Co-morbid acute or chronic conditions (including type I diabetes mellitus, other neurological conditions such as Parkinson's disease, psychiatric disorders, and severe or unstable medical conditions) that could confound assessments or would, in the judgment of the investigator, make the subject inappropriate for entry into this study

9. Any of the following findings on previous CT/MRI or on screening MRI:

Brain Location: Anywhere, Exclusionary Finding: Malignant tumour, Size: Any, Excl. #:

Any

Brain Location: Anywhere, Exclusionary Finding: Tumour w/ sig. mass effect, Size:

Sufficient for mass effect, Excl. #: Any

Brain Location: Anywhere, Exclusionary Finding: Vascular malformations, Size: Any, Excl. #: Any

Brain Location: Anywhere, Exclusionary Finding: Subdural hematoma, Size: Any, Excl. #:

Any

Brain Location: Anywhere, Exclusionary Finding: Intracerebral hemorrhage, Size: Any, Excl. #: Any

Brain Location: Anywhere, Exclusionary Finding: Cerebral microbleeds, Size: Any, Excl. #: more than 5

Brain Location: Cortex, Exclusionary Finding: Superficial siderosis, Size: Any, Excl. #: more than 1 instance of focal SS

Brain Location: Cortex, Exclusionary Finding: Ischemic infarct, Size: >1.5 cm in diameter, Excl. #: Any

Brain Location: Cortex, Exclusionary Finding: Ischemic infarct, Size: ≤1.5 cm in diameter, Excl. #: more than 1

Brain Location: Periventricular Exclusionary Finding: Fazekas score 3 with White matter hyperintensity band along the lateral surface of the ventricles, Size: >0.5 cm in width Excl. #: Any

Brain Location: White matter, Exclusionary Finding:Ischemic infarct, Size: >1.5 cm in diameter, Excl. #:Any

Brain Location: White matter, Exclusionary Finding: Ischemic infarct, Size: 1.0-1.5 cm in diameter, Excl. #: more than 2

Brain Location: Basal ganglia, Exclusionary Finding: Ischemic infarct, Size: >1.0 cm in diameter, Excl. #: Any

Brain Location: Basal ganglia and white matter, Exclusionary Finding: Ischemic infarct, Size: ≤1.0 cm in diameter, Excl. #: more than 4

Brain Location: Thalamus, Exclusionary Finding: Strategic infarct, Size: Any, Excl. #:

Any

Brain Location: Hippocampus, Exclusionary Finding: Strategic infarct, Size: Any, Excl#.: Any

10. Inability to perform the study procedures, including claustrophobia or contraindications for MRI

11. Currently on or has taken an angiotensin receptor blocker within 12 months of randomization visit

12. Resides in a nursing home (participants who reside in retirement homes may be included if they have a study partner who meets inclusion criterion #8)

13. Current major depression by clinical history or score greater than 18 on the Cornell Scale for Depression in Dementia

14. Documented potential cardiac source of brain infarction such as mechanical valve or atrial fibrillation that is untreated or treated with warfarin or an antiplatelet agent; atrial fibrillation treated with a novel oral anticoagulant is permitted, as is a history of remote, transient atrial fibrillation that has not recurred