Reducing pathology in Alzheimer's disease through angiotensin targeting

Phase 2

Completed

• Conditions: Topic: Dementias and Neurodegenerative Diseases Research Network; Subtopic: Dementia; Nervous System Diseases; Disease: Dementia; Alzheimer disease, unspecified

• Registration Number: ISRCTN93682878
• Lead Sponsor: orth Bristol NHS Trust (UK)

Brief Summary

2018 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/29226862 protocol 2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34687634/ (added 26/10/2021)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-09-10
• Study Completion: 2019-07-31
• Last Update Posted: 8 November 2021

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 261

Inclusion Criteria

1. Age =55 years
2. A Mini Mental State Examination (MMSE) score of 18-28 or Montreal Cognitive Assessment (MoCA) of 12-24
3. A modified Hachinski score (56) of 5 or less
4. A previous CT or MRI scan consistent with a diagnosis of AD
5. The presence of an informant who is willing to participate in the study
6. Capacity to consent for themselves as judged by a member of the research teamwith appropriate training and experience

Exclusion Criteria

Patients will be excluded/ineligible if they have any of the following:
1. Receiving ACE-Inhibitors; AT1RAs, aliskiren or potassium sparing diuretics
2. Known intolerance to sartans
3. Medically unsuitable for, or unwilling to have, an MRI scan
4. Consistent baseline BP of <115/70 mmHg or >160/110 mmHg
5. A fall in BP on standing of >20/10 mmHg associated with clinically significant symptoms or a fall >30/15 mmHg
6. Previous cerebrovascular accident (CVA), with significant residual impairment (Transient Ischaemic Attack (TIA) is NOT an exclusion)
7. Hypertrophic cardiomyopathy; or significant aortic valve stenosis
8. Estimated creatinine clearance of < 30 mL/min/1.73m2, or previous severe renal impairment with a sartan or ACE inhibitor
9. Evidence of liver disease or significant LFT derangement (Aspartate transaminase (AST)/ Alkaline Phosphatase (AP/ALP)/ Bilirubin greater than 2 x upper limit of normal) in the previous 12 months
10. Primary neurodegenerative diseases or potential causes of dementia other than AD.
11. Females who have not yet reached the menopause (defined as having a period in the previous 12 months) who test positive for pregnancy, are unwilling to take a pregnancy test prior to trial entry, or are unwilling to undertake adequate precautions to prevent pregnancy for the duration of the trial
12. Any severe co-incident medical disease, or other factor inhibiting compliance with the study medication or follow up schedule e.g. participant unlikely to survive the trial follow up period due to a terminal comorbid condition
13. Participation in a previous CTIMP within 6 months of RADAR trial entry
14. Severe hippocampal atrophy as identified at baseline (or previous) MRI scan according to the Sheltens Scale

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in whole brain volume, measured using volumetric MRI (vMRI); Timepoint(s): after 12 months of treatment after randomisation

Secondary Outcome Measures

Name	Time	Method
<br> 1. Rates of AD progression, assessed by changes in cognitive assessments, measures of activities of daily living and quality of life<br> 2. Change to the level of CBF, measured by arterial spin labelling (ASL) techniques<br> 3. Change to the level of white matter hyperintensities, measured by MRI<br> 4. Change in BP<br> 5. Measure of association between MRI measures of atrophy and rate of cognitive decline<br> 6. Level of drug compliance and tolerability (particular consideration to non-hypertensive patients? tolerability), although past studies report that drop out and side effects are not a major problem<br>