Telmisartan vs. Perindopril in Mild-Moderate Alzheimer's Disease Patients (SARTAN-AD)

May 3, 2022 updated by: Dr. Sandra E Black, Sunnybrook Health Sciences Centre

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N1
      • Lethbridge, Alberta, Canada, T1K 6T5
        • Recruiting
        • University of Lethbridge
        • Principal Investigator:
          • John Kennedy, MD
        • Principal Investigator:
          • Robert Sutherland, PhD
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 2B5
        • Recruiting
        • UBC Hospital
        • Contact:
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Recruiting
        • Hamilton General Hospital
        • Contact:
          • Shuhira Himed
          • Phone Number: 44468 905.521.2100
          • Email: himed@hhsc.ca
        • Principal Investigator:
          • Demetrios (James) Sahlas, MD
      • London, Ontario, Canada, N6C 4R3
        • Not yet recruiting
        • Parkwood Institute
        • Principal Investigator:
          • Michael Borrie, MD
        • Contact:
      • Toronto, Ontario, Canada, M5B 1W8
        • Recruiting
        • St. Michael's Hospital
        • Principal Investigator:
          • Corinne Fischer, MD
      • Toronto, Ontario, Canada, M4N 3M5
      • Toronto, Ontario, Canada, M6A 2E1
        • Recruiting
        • Baycrest Health Sciences
        • Contact:
        • Principal Investigator:
          • Howard Chertkow, MD
      • Toronto, Ontario, Canada
        • Recruiting
        • Centre for Addiction and Mental Health (CAMH)
        • Principal Investigator:
          • Sanjeev Kumar, MD
        • Contact:
      • Toronto, Ontario, Canada, M4G 3E8
        • Completed
        • Centre for Memory and Aging

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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:

    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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Telmisartan
Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)
Drug: Telmisartan
Telmisartan 40 mg or 80 mg/day (depending on age and tolerability)
Other Names:
  • Micardis
Active Comparator: Perindopril
Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)
Drug: Perindopril
Perindopril 2 mg, 4 mg or 8 mg/day (depending on kidney function and tolerability)
Other Names:
  • Coversyl

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hippocampal volume
Time Frame: 12 months
Change in hippocampal volume measurements after 12 months of treatment
12 months
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
12 months
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
6 and 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neuropsychiatric Measures
Time Frame: 6 & 12 months
Assess the comparative treatment responsiveness of neuropsychiatric measures and obtain pilot data
6 & 12 months
Treatment responsiveness of Diffusion Tensor Imaging (DTI)
Time Frame: 12 months
Assess the comparative treatment responsiveness of Diffusion Tensor Imaging (DTI) and obtain pilot data
12 months
Treatment responsiveness of resting state functional MRI (rsfMRI)
Time Frame: 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.
12 months
Quality of Life - Caregiver burden
Time Frame: 12 months
Assess the comparative response of caregiver burden after treatment using Zarit burden interview.
12 months
Quality of Life - Health-related
Time Frame: 12 months
Assess health related quality of life after treatment using EQ-5D-5L questionnaire.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sunnybrook Health Sciences Centre

Collaborators

Alzheimer's Drug Discovery Foundation
Weston Brain Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Anticipated)

September 1, 2023

Study Completion (Anticipated)

September 1, 2023

Study Registration Dates

First Submitted

November 29, 2013

First Submitted That Met QC Criteria

March 10, 2014

First Posted (Estimate)

March 12, 2014

Study Record Updates

Last Update Posted (Actual)

May 4, 2022

Last Update Submitted That Met QC Criteria

May 3, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 148-2013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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