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

Alzheimer's Disease Clinical Trial

— SARTAN-AD  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02085265
• Other study ID #: 148-2013
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: September 2023

Study information

• Verified date: May 2022
• Source: Sunnybrook Health Sciences Centre
• Contact: Sandra Black, MD
• Phone: 416.480.4551
• Email: sandra.black[@]sunnybrook.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	University of Lethbridge	Lethbridge	Alberta
Canada	Parkwood Institute	London	Ontario
Canada	Baycrest Health Sciences	Toronto	Ontario
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario
Canada	Centre for Memory and Aging	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	UBC Hospital	Vancouver	British Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Alzheimer's Drug Discovery Foundation, Weston Brain Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neuropsychiatric Measures	Assess the comparative treatment responsiveness of neuropsychiatric measures and obtain pilot data	6 & 12 months
Other	Treatment responsiveness of Diffusion Tensor Imaging (DTI)	Assess the comparative treatment responsiveness of Diffusion Tensor Imaging (DTI) and obtain pilot data	12 months
Other	Treatment responsiveness of resting state functional MRI (rsfMRI)	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
Other	Quality of Life - Caregiver burden	Assess the comparative response of caregiver burden after treatment using Zarit burden interview.	12 months
Other	Quality of Life - Health-related	Assess health related quality of life after treatment using EQ-5D-5L questionnaire.	12 months
Primary	Ventricular enlargement	Change in ventricular size, on 3D T1 MR imaging, after 12 months of treatment	12 months
Primary	Safety - Blood pressure	Change in blood pressure (BP) measurements after 12 months of treatment.	12 months
Primary	Safety - Vital signs	Change in vital sign (heart rate, pulse) measurements after 12 months of treatment.	12 months
Primary	Safety - Electrolytes	Change in electrolyte measurements (Na, K) after 12 months of treatment.	12 months
Primary	Safety - Adverse Events	Adverse events and serious adverse events over 12 months of treatment.	12 months
Secondary	Hippocampal volume	Change in hippocampal volume measurements after 12 months of treatment	12 months
Secondary	Grey/White matter volume	Volume of grey and white matter in the cingulate, parietotemporal and dorsolateral frontal regions after 12 months of treatment	12 months
Secondary	Cognitive and functional measures	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