Condition category
Nervous System Diseases
Date applied
10/09/2013
Date assigned
10/09/2013
Last edited
14/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Alzheimer's disease profoundly affects memory and brain function in older individuals. The disease starts slowly and worsens to the extent that people eventually need 24-hour care - a heart-breaking, exhausting and often costly reality for family and health services. With an ageing population, Alzheimer's disease care provision needs will increase with an impact on NHS healthcare costs. In this study we will investigate whether losartan, a well-tolerated blood pressure drug, can complement current therapies for Alzheimer's disease. We believe losartan will slow down the progression of Alzheimer's disease by improving brain blood flow and altering chemical pathways that affect abnormal proteins that accumulate in Alzheimer's disease and cause brain shrinkage. This study will test the effect of losartan on brain tissue changes in patients diagnosed with Alzheimer's disease.

Who can participate?
The study aims to recruit 228 patients who have mild to moderate Alzheimer's disease, who meet the trial eligibility criteria and are able to travel to one of 20-25 RADAR sites across the UK.

What does the study involve?
Each participant recruited into the study will be randomly allocated to receive either losartan or a placebo (dummy tablet) once a day for 12 months. In addition to memory tests, we will use brain imaging to measure whether losartan reduces shrinkage (atrophy) in brain areas that are strongly linked with reduced memory function and improves brain blood flow.

What are the possible benefits and risks of participating?
Possible benefits are unclear, but if the hypothesis is correct, then if you are allocated to receive the active medication this may help slow the progression of Alzheimer's disease, but it must be stressed that there is no guarantee. Possible risks include experiencing side-effects from the study drug, which include dizziness, low blood pressure, feeling tired or weak, too little sugar in the blood, and too much potassium in the blood.

Where is the study run from?
The study is a collaborative project led by NHS North Bristol Trust, in collaboration with the University of Bristol, Bristol Randomised Trial Collaboration (UKCRC Registered Clinical Trials Unit).

When is the study starting and how long is it expected to run for?
The study aims to start recruitment in October 2013. Each participant will be enrolled for 12 months. The study will run until February 2017.

Who is funding the study?
The Department of Health's National Institute for Health Research (NIHR) (UK).

Who is the main contact?
Prof. Patrick Kehoe
radar-trial@bristol.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Beth Howden

ORCID ID

Contact details

RADAR Coordinating Centre
School of Social and Community Medicine
Faculty of Health Sciences
University of Bristol
Oakfield House
Oakfield Grove
Bristol
BS8 2BN
United Kingdom
+44 (0)117 331 3317
radar-trial@bristol.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

15071

Study information

Scientific title

Reducing pathology in Alzheimer's disease through angiotensin targeting - the RADAR trial: a phase II, two-arm, double-blind, placebo-controlled, randomised trial to evaluate the effect of losartan on brain tissue changes in patients diagnosed with Alzheimer's disease

Acronym

RADAR

Study hypothesis

Alzheimer's disease (AD) profoundly affects memory and brain function. It is a slow progressive disease that can last for a number of years - a heartbreaking, exhausting and often costly reality for family and health services. With an ageing population, AD health care provision needs will significantly rise. Existing treatments only temporarily treat specific imbalances in the brain but as yet there is no cure for AD. Losartan, a well-tolerated blood pressure drug, blocks a chemical pathway called angiotensin II which prevent the release of vital memory chemicals in the brain. Losartan improves memory problems in mice designed to have Alzheimer's features and in people given chemicals to temporarily affect their memories. People who have previously taken losartan, have lower risk of developing AD compared to other blood pressure drugs. These drugs may also slow the rate of deterioration in patients with Alzheimer's. This multi-centre clinical trial will investigate if losartan could complement current treatments for AD. We believe losartan will slow down the progression of AD by improving brain blood flow and altering chemical pathways that cause brain cell damage, brain shrinkage and memory problems in AD. Brain images will measure if losartan reduces brain shrinkage, which we know is strongly linked with reduced memory function. Blood samples taken within this study will be analysed to see whether losartan changed proteins that may be predictive of rates of disease progression. RADAR will offer great value for money if this cheap (3-4p per day) well tolerated drug is found to be beneficial in AD. RADAR will provide the requisite evidence needed to justify a much larger multicentre trial that will be needed to provide the final proof of losartan's benefit in AD.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=15071

Ethics approval

South East Wales Research Ethics Committee C, 19/02/2013, ref: 12/WA/0338

Study design

Interventional phase II double-blind placebo-controlled randomised treatment trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Dementias and Neurodegenerative Diseases Research Network; Subtopic: Dementia; Disease: Dementia

Intervention

Drug Treatment, Group I: Placebo
Group II: Losartan

During the open-label phase losartan will be given at 25mg dose for 7 days and then 100mg for 7 days, followed by placebo for 4 days up to two weeks prior to the first MRI scan. Following the MRI, if suitable to proceed to the randomised phase, participants will be randomly allocated to receive either losartan at 25mg for 7 days followed by 100mg for the remainder of the trial, or placebo for the remainder of the trial. During the randomised phase patients will not know whether they are taking losartan or placebo.

Duration of intervention: Once a day for 12 months
The total follow up period is 12 months and at least 4 days (to allow a washout period after finishing the trial treatment before the final MRI).

The sample size will be recruited from at least 20 sites across the UK over 2 years which currently equates to approximately 12 patients per site at a monthly recruitment of 1 patient per month.

Intervention type

Drug

Phase

Phase II

Drug names

Losartan

Primary outcome measures

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

Secondary outcome measures

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 (particular consideration to non-hypertensive patients’ tolerability) though past studies report that drop out and side effects are not a major problem.

Overall trial start date

01/03/2013

Overall trial end date

28/02/2017

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 228; UK Sample Size: 228

Participant 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

Recruitment start date

31/10/2013

Recruitment end date

01/11/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Bristol
Bristol
BS8 2BN
United Kingdom

Sponsor information

Organisation

North Bristol NHS Trust (UK)

Sponsor details

Trust Headquarters
Beckspool Road
Frenchay
Bristol
B16 1JE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.nbt.nhs.uk/

Funders

Funder type

Government

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 14/12/2015 the overall trial end date was changed from 31/05/2015 to 28/02/2017.