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

NCT ID: NCT02085265

Last Updated: 2025-05-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2025-02-28

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Telmisartan

Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)

Group Type: EXPERIMENTAL

Telmisartan

Intervention Type: DRUG

Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)

Perindopril

Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)

Group Type: ACTIVE_COMPARATOR

Perindopril

Intervention Type: DRUG

Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)

Interventions

Perindopril

Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)

Intervention Type: DRUG

Telmisartan

Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)

Intervention Type: DRUG

Other Intervention Names

Coversyl; Micardis

Eligibility Criteria

Exclusion 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.

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:

Exclusionary Finding: Malignant tumour Brain Location: Anywhere Size: Any Exclusionary Number: Any

Exclusionary Finding: Tumour with significant mass effect Brain Location: Anywhere Size: Sufficient for mass effect Exclusionary Number: Any

Exclusionary Finding: Vascular malformations Brain Location: Anywhere Size: Any Exclusionary Number: Any

Exclusionary Finding: Subdural hematoma Brain Location: Anywhere Size: Any Exclusionary Number: Any

Exclusionary Finding: Intracerebral hemorrhage Brain Location: Anywhere Size: Any Exclusionary Number: Any

Exclusionary Finding: Cerebral microbleeds, Brain Location: Anywhere Size: Any Exclusionary Number: more than 5

Exclusionary Finding: Superficial siderosis (SS) Brain Location: Cortex Size: Any Exclusionary Number: >1 instance of focal SS

Exclusionary Finding: Ischemic infarct Brain Location: Cortex Size: >1.5 cm in diameter Exclusionary Number: Any

Exclusionary Finding: Ischemic infarct Brain Location: Cortex Size: ≤1.5 cm in diameter Exclusionary Number: more than 1

Exclusionary Finding: Fazekas score 3 with white matter hyperintensity band along the lateral surface of the ventricles >0.5 cm in width

Exclusionary Finding: Ischemic infarct Brain Location: White matter Size: >1.5 cm in diameter Exclusionary Number: Any

Exclusionary Finding: Ischemic infarct Brain Location: White matter Size: 1.0-1.5 cm in diameter Exclusionary Number: More than 2

Exclusionary Finding: Ischemic infarct Brain Location: Basal ganglia Size: >1.0 cm in diameter Exclusionary Number: Any

Exclusionary Finding: Ischemic infarct Brain Location: Basal ganglia and white matter Size: ≤1.0 cm in diameter Exclusionary Number: More than 4

Exclusionary Finding: Strategic infarct Brain Location: Thalamus Size: Any Exclusionary Number: Any

Exclusionary Finding: Strategic infarct Brain Location: Hippocampus, Size: Any Exclusionary Number: 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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alzheimer's Drug Discovery Foundation

OTHER

Sponsor Role: collaborator

Weston Brain Institute

OTHER

Sponsor Role: collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Sandra E Black

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sandra Black, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Krista Lanctot, PhD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Research Institute

Locations

University of Calgary

Calgary, Alberta, Canada

University of Lethbridge

Lethbridge, Alberta, Canada

UBC Hospital

Vancouver, British Columbia, Canada

Hamilton General Hospital

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

Countries

Canada

Other Identifiers

148-2013

Identifier Type: -

Identifier Source: org_study_id