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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02085265
Recruitment Status : Recruiting
First Posted : March 12, 2014
Last Update Posted : May 4, 2022
Sponsor:
Collaborators:
Alzheimer's Drug Discovery Foundation
Weston Brain Institute
Information provided by (Responsible Party):
Dr. Sandra E Black, Sunnybrook Health Sciences Centre

Study Description
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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).

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Perindopril Drug: Telmisartan Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The SARTAN-AD Trial: A Randomized, Open Label, Proof of Concept Study of Telmisartan vs. Perindopril in Mild-Moderate Alzheimer's Disease Patients
Study Start Date : March 2014
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: 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 Name: Coversyl


Outcome Measures
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Primary Outcome Measures :
  1. Ventricular enlargement [ Time Frame: 12 months ]
    Change in ventricular size, on 3D T1 MR imaging, after 12 months of treatment

  2. Safety - Blood pressure [ Time Frame: 12 months ]
    Change in blood pressure (BP) measurements after 12 months of treatment.

  3. Safety - Vital signs [ Time Frame: 12 months ]
    Change in vital sign (heart rate, pulse) measurements after 12 months of treatment.

  4. Safety - Electrolytes [ Time Frame: 12 months ]
    Change in electrolyte measurements (Na, K) after 12 months of treatment.

  5. Safety - Adverse Events [ Time Frame: 12 months ]
    Adverse events and serious adverse events over 12 months of treatment.


Secondary Outcome Measures :
  1. Hippocampal volume [ Time Frame: 12 months ]
    Change in hippocampal volume measurements after 12 months of treatment

  2. 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

  3. 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


Other Outcome Measures:
  1. Neuropsychiatric Measures [ Time Frame: 6 & 12 months ]
    Assess the comparative treatment responsiveness of neuropsychiatric measures and obtain pilot data

  2. 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

  3. 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.

  4. Quality of Life - Caregiver burden [ Time Frame: 12 months ]
    Assess the comparative response of caregiver burden after treatment using Zarit burden interview.

  5. Quality of Life - Health-related [ Time Frame: 12 months ]
    Assess health related quality of life after treatment using EQ-5D-5L questionnaire.


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02085265


Contacts
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Contact: Sandra Black, MD 416.480.4551 sandra.black@sunnybrook.ca
Contact: Ljubica Zotovic, MD 416.480.6100 ext 3004 ljubica.zotovic@sunnybrook.ca

Locations
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Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada, T2N 4N1
Contact: Karyn Fischer, RN    403-220-8394    Karyn.Fischer@albertahealthservices.ca   
Principal Investigator: Eric Smith, MD         
University of Lethbridge Recruiting
Lethbridge, Alberta, Canada, T1K 6T5
Principal Investigator: John Kennedy, MD         
Principal Investigator: Robert Sutherland, PhD         
Canada, British Columbia
UBC Hospital Recruiting
Vancouver, British Columbia, Canada, V6T 2B5
Contact: Michele Assaly, M.A.    604-822-1782    Michele.Assaly@vch.ca   
Principal Investigator: Robin Hsiung, MD         
Canada, Ontario
Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Shuhira Himed    905.521.2100 ext 44468    himed@hhsc.ca   
Principal Investigator: Demetrios (James) Sahlas, MD         
Parkwood Institute Not yet recruiting
London, Ontario, Canada, N6C 4R3
Contact: Rebecca Shostak    519-685-4292 ext 45609    rebecca.shostak@sjhc.london.on.ca   
Principal Investigator: Michael Borrie, MD         
Centre for Memory and Aging Completed
Toronto, Ontario, Canada, M4G 3E8
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Anna Malakhova    416-480-6100 ext 63867    anna.malakhova@sunnybrook.ca   
Contact: Ljubica Zotovic    416-480-6100 ext 3004    ljubica.zotovic@sunnybrook.ca   
Principal Investigator: Sandra Black, MD         
St. Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Principal Investigator: Corinne Fischer, MD         
Baycrest Health Sciences Recruiting
Toronto, Ontario, Canada, M6A 2E1
Contact: Naga Avvaru    (416) 785-2500 ext 3627    navvaru@research.baycrest.org   
Principal Investigator: Howard Chertkow, MD         
Centre for Addiction and Mental Health (CAMH) Recruiting
Toronto, Ontario, Canada
Contact: Dewi Clark    416-535-8501 ext 30409    Dewi.Clark@camh.ca   
Principal Investigator: Sanjeev Kumar, MD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Alzheimer's Drug Discovery Foundation
Weston Brain Institute
Investigators
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Principal Investigator: Sandra Black, MD Sunnybrook Health Sciences Centre
Principal Investigator: Krista Lanctot, PhD Sunnybrook Research Institute
More Information
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Responsible Party: Dr. Sandra E Black, Principal Investigator, Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT02085265    
Other Study ID Numbers: 148-2013
First Posted: March 12, 2014    Key Record Dates
Last Update Posted: May 4, 2022
Last Verified: May 2022
Keywords provided by Dr. Sandra E Black, Sunnybrook Health Sciences Centre:
Alzheimer's Disease
Perindopril
Telmisartan
Brain atrophy
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
 Telmisartan
Perindopril
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors