Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000214336
Ethics application status
Approved
Date submitted
2/02/2017
Date registered
9/02/2017
Date last updated
24/11/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of statins on cognition in older adults with dementia
Scientific title
A pilot study of N-of-1 trials to determine the effects of deprescribing statins on short-term cognition in older adults with dementia
Secondary ID [1] 290386 0
None
Universal Trial Number (UTN)
U1111-1189-0576
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dementia 300702 0
Cognitive impairment 300703 0
Condition category
Condition code
Neurological 300548 300548 0 0
Dementias
Neurological 300549 300549 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomly assigned to one of two treatment arms: Arm 1, Placebo-Statin-Placebo; or Arm 2, Statin-Placebo-Statin.
Patients will be on each period of either 'statin' or 'placebo' for 5 weeks with no washout, resulting in a total trial period of 15 weeks.
Patients will be taking their normal statin treatment during their 'statin' period(s), with a placebo replacement during 'placebo' period(s).
Adherence will be tested by using a pill count at the end of each intervention period.
Intervention code [1] 296214 0
Treatment: Drugs
Comparator / control treatment
Patients will be compared between having a placebo, and when on their normal statin treatment - which will act as a control period.
Control group
Active

Outcomes
Primary outcome [1] 299964 0
Mean change in Alzheimer's Disease Assessment Scale - Cognitive Portion (ADAS-CoG) score
Timepoint [1] 299964 0
Baseline, and at 5, 10 and 15-weeks after enrolment in the trial.
Secondary outcome [1] 328712 0
Mean change in Quality of Life in Alzheimer's Disease (QoL-AD) score
Timepoint [1] 328712 0
Baseline, and at 5, 10 and 15-weeks after enrolment in the trial.
Secondary outcome [2] 328713 0
Mean change in Short Performance Physical Battery score
Timepoint [2] 328713 0
Baseline, and at 5, 10 and 15-weeks after enrolment in the trial
Secondary outcome [3] 328714 0
Mean change in Cambridge Behavioural Inventory score
Timepoint [3] 328714 0
Baseline, and at 5, 10 and 15-weeks after enrolment in the trial

Eligibility
Key inclusion criteria
Mini-Mental State Examination (MMSE) score of between 10 and 23 and/or clinical diagnosis of dementia; currently taking any statin for at least 6 months
Minimum age
80 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Too unwell to participate, or in the terminal stage of any illness; active cancer diagnosis; taking a combination statin;

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomised by a third-party (Clinical Trials Pharmacy at the Royal North Shore Hospital, St Leonards, Sydney) upon patient enrolment into the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number generator on Microsoft Excelt
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Multiple N-of-1 trials with participants randomised to either Treatment Arm 1 (Placebo-Statin-Placebo) or Treatment Arm 2 (Statin-Placebo-Statin)
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is a pilot study so no formal power calculation was used. We aim to recruit 30 participants for this study which can then inform future trials.

Data analysis will be conducted within each N-of-1 trial and results combined across them. We will follow the intention-to-treat principal of analyses. The difference in mean ADAS-CoG scores between statin therapy and placebo is the pre-specified primary outcome, with a difference of 4 to be considered clinically significant.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
18/01/2017
Date of last participant enrolment
Anticipated
20/02/2017
Actual
18/01/2017
Date of last data collection
Anticipated
11/06/2017
Actual
18/05/2017
Sample size
Target
30
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6862 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 14532 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 294779 0
University
Name [1] 294779 0
University of Sydney
Country [1] 294779 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
Faculty of Pharmacy
Pharmacy and Bank Building
Science Road
Camperdown
NSW
2006
Country
Australia
Secondary sponsor category [1] 293625 0
None
Name [1] 293625 0
Address [1] 293625 0
Country [1] 293625 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296186 0
North Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 296186 0
Level 13
Kolling Building
Royal North Shore Hospital
Reserve Road
St Leonards
NSW 2065
Ethics committee country [1] 296186 0
Australia
Date submitted for ethics approval [1] 296186 0
25/07/2016
Approval date [1] 296186 0
10/10/2016
Ethics approval number [1] 296186 0
HREC/16/HAWKE/286

Summary
Brief summary
Background:
Statins are effective in treating dyslipidaemia in older adults, reducing the cardiovascular related morbidity – however their adverse effects are more common and harmful amongst older adults. Additionally, the impact on cognition is unclear, with previous studies producing mixed results. The N-of-1 method has been demonstrated to be a feasible method of conducting deprescribing trials, generating strong-patient specific evidence as to the effects of discontinuing statin use on cognition.

Aims:
1. To determine the effect on cognition of discontinuation and rechallenge with statins.
2. To determine the effects on quality of life and functional status of discontinuation and rechallenge with statins.

Methods:
A pilot interventional study of 30 older adults 80 years of age or older admitted to Royal North Shore Hospital, Sydney with current dementia diagnosis, and taking statins for at least 6 months will be conducted. Participants will be randomly assigned to statin and placebo treatment pairs with discontinuation and rechallenge of statins over the course of 4-months. At baseline (0-weeks), recruited patients will be subsequently randomised into either continuation of active statin treatment or placebo replacement for a period of 5-weeks. Participants will be followed at 5-weeks (Visit 2), 10-weeks (Visit 3) and 15-weeks (Visit 4). At each visit, patients will be crossed over into opposing intervention, either continuation of active statin or placebo. The primary outcome will be measured using the cognitive portion of the Alzheimer’s Disease Assessment Score (ADAS-CoG), which assesses the level of cognitive impairment on a 30-point scale with a psychometric test. The patients’ general practitioners will be contacted two months after trial completion to ascertain whether patients had discontinued, lowered dose, or continued their statin medication.

Hypothesis:
We hypothesise that patients will have improved cognition and quality of life when on placebo compared to when on statins.
Trial website
None
Trial related presentations / publications
None
Public notes
Attachments [1] 1201 1201 0 0
/AnzctrAttachments/371713-Letter - HREC FINAL approval - HREC Exec meeting 10 October 2016 - RESP 16 191.pdf (Ethics approval)
Attachments [2] 1202 1202 0 0
/AnzctrAttachments/371713-PISCF Patient Version 3 26.09.16 Clean.docx (Participant information/consent)
Attachments [3] 1203 1203 0 0
/AnzctrAttachments/371713-PISCF Person Responsible Version 3 26.09.16 Clean.docx (Participant information/consent)

Contacts
Principal investigator
Name 69910 0
Mr Alexander Clough
Address 69910 0
Pharmacy and Bank Building
Science Road
University of Sydney
Camperdown
NSW 2006
Country 69910 0
Australia
Phone 69910 0
+61414161528
Fax 69910 0
Email 69910 0
[email protected]
Contact person for public queries
Name 69911 0
Mr Alexander Clough
Address 69911 0
Pharmacy and Bank Building
Science Road
University of Sydney
Camperdown
NSW 2006
Country 69911 0
Australia
Phone 69911 0
+61414161528
Fax 69911 0
Email 69911 0
[email protected]
Contact person for scientific queries
Name 69912 0
Mr Alexander Clough
Address 69912 0
Pharmacy and Bank Building
Science Road
University of Sydney
Camperdown
NSW 2006
Country 69912 0
Australia
Phone 69912 0
+61414161528
Fax 69912 0
Email 69912 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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