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

Overview

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).

Full Title of Study: “The SARTAN-AD Trial: A Randomized, Open Label, Proof of Concept Study of Telmisartan vs. Perindopril in Mild-Moderate Alzheimer’s Disease Patients”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2022

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

  • Drug: Perindopril
    • Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)
  • Drug: Telmisartan
    • Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)

Arms, Groups and Cohorts

  • Experimental: Telmisartan
    • Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)
  • Active Comparator: Perindopril
    • Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)

Clinical Trial Outcome Measures

Primary Measures

  • Ventricular enlargement
    • Time Frame: 12 months
    • Change in ventricular size, on 3D T1 MR imaging, after 12 months of treatment
  • Safety – Blood pressure
    • Time Frame: 12 months
    • Change in blood pressure (BP) measurements after 12 months of treatment.
  • Safety – Vital signs
    • Time Frame: 12 months
    • Change in vital sign (heart rate, pulse) measurements after 12 months of treatment.
  • Safety – Electrolytes
    • Time Frame: 12 months
    • Change in electrolyte measurements (Na, K) after 12 months of treatment.
  • Safety – Adverse Events
    • Time Frame: 12 months
    • Adverse events and serious adverse events over 12 months of treatment.

Secondary Measures

  • Hippocampal volume
    • Time Frame: 12 months
    • Change in hippocampal volume measurements after 12 months of treatment
  • Grey/White matter volume
    • Time Frame: 12 months
    • Volume of grey and white matter in the cingulate, parietotemporal and dorsolateral frontal regions after 12 months of treatment
  • Cognitive and functional measures
    • Time Frame: 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sunnybrook Health Sciences Centre
  • Collaborator
    • Alzheimer’s Drug Discovery Foundation
  • Provider of Information About this Clinical Study
    • Principal Investigator: Dr. Sandra E Black, Principal Investigator – Sunnybrook Health Sciences Centre
  • Overall Official(s)
    • Sandra Black, MD, Principal Investigator, Sunnybrook Health Sciences Centre
    • Krista Lanctot, PhD, Principal Investigator, Sunnybrook Research Institute
  • Overall Contact(s)
    • Sandra Black, MD, 416.480.4551, sandra.black@sunnybrook.ca

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.