Alzheimer's Disease
Conditions
Interventions
Trade Name: Losartan potassium 25 mg Film-coated Tablets
Product Name: Losartan 25mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: losartan potassium
CAS Number: 114798-26-4
Concentrati
Sponsors
North Bristol NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age=55 years • A MMSE score of 15-28 (equivalent to a previous Montreal Cognitive Assessment (MoCA) of 7-26). NB all patients must undergo an MMSE as part of their eligibility assessment for RADAR, but may be screened on the basis of a previous MMSE/MoCA score. • A modified Hachinski score of 5 or less • A previous CT or MRI scan consistent with a diagnosis of AD • The presence of an informant who is willing to participate in the study • Capacity to consent for themselves as judged by a member of the research team with appropriate training and experience Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 78 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: • Receiving ACE-Inhibitors; AT1RAs, aliskiren or potassium sparing diuretics • Known intolerance or renal problems with ACE-inhibitors or sartans • Medically unsuitable for, or unwilling to have, an MRI scan • Consistent baseline BP of 160/110 mmHg • A fall in BP on standing of >20/10 mmHg associated with clinically significant symptoms or a fall >30/15 mmHg • Previous cerebrovascular accident (CVA), with significant residual impairment (Transient Ischaemic Attack (TIA) is NOT an exclusion) • Hypertrophic cardiomyopathy; or significant aortic valve stenosis • Estimated glomerular filtration rate (eGFR) of < 30 mL/min/1.73m2Evidence of liver disease or significant LFT derangement (Aspartate transaminase (AST)/ Alkaline Phosphatase (AP/ALP)/ Bilirubin greater than 2 x upper limit of normal) • Potassium (K) greater than 6 on non-haemolysed sample • Primary neurodegenerative diseases or potential causes of dementia other than AD. • 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 • 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 • Participation in a previous CTIMP within 6 months of RADAR trial entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To what extent does angiotensin II signalling blockade by losartan reduce MRI-based measures of brain atrophy (wasting) in Alzheimer's Disease? Angiotensin II is a small molecule that is already well known for being responsible for the contraction of blood vessels which in turn increases blood pressure. More recent evidence over the last decades has come to light of how angiotensin II is also very promiscuous in biochemical terms. Angiotensin II (or Ang II) is very involved in processes that increase inflammation; it inhibits the release of the chemical acetylcholine which is vital for memory formation in the brain; it is heavily involved with how cells regulate calcium levels which in turn can impact on levels of cell death and the activation of other mechanisms that also damage cells. All of these facets are characteristics of the detrimental processes that are all very active in the brain of patients with Alzheimer's disease.;Secondary Objective: Does losartan slow the rate of cognitive decline in AD? Does losartan improve daily functioning and quality of life in AD? Does losartan improve blood flow to the brain and improve white matter hyperintensities volume (evidence of vascular damage) in people with AD? What is the association between MRI measures of brain shrinkage and the rate of cognitive decline following one year of treatment with losartan? In elderly hypertensive and normotensive AD patients, what is the level of tolerability and compliance to taking 100mg of losartan once daily for 12 months? ;Primary end point(s): Change in whole brain volume after 12 months of treatment after randomisation, measured using volumetric MRI (vMRI). ;Timepoint(s) of evaluation of this end point: 12 months 4 days after randomisation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) rates of AD progression as assessed by changes in cognitive assessments, measures of activities of daily living and quality of life; 2) change to the level of CBF measured by arterial spin labelling (ASL) techniques; 3) change to the level of white matter hyperintensities by MRI; 4) change in BP 5) measure of association between MRI measures of atrophy and rate of cognitive decline; 6) level of drug compliance and tolerability. ;Timepoint(s) of evaluation of this end point: 1) 6 months and 12 months 4 days after randomisation 2) 12 months 4 days after randomisation. 3) 12 months 4 days after randomisation. 4) 3 months, 6 months, 9 months and 12 months 4 days after randomisation. 5) 12 months 4 days after randomisation. 6) 12 months 4 days after randomisation. | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Manager
North Bristol NHS Trust
Outcome results
None listed