Towards Onset Prevention of COGnition decline in adults with Down syndrome (the TOP-COG study)

Plain English summary of protocol

Background and study aims
This study is to find out whether it will be feasible to conduct a larger study to test whether a medication called simvastatin can prevent the onset of dementia in adults with Down syndrome. A lot of people with Down syndrome develop memory problems or Alzheimer’s disease/dementia in middle age. This is disabling, causing loss of skills and abilities. Over time, a naturally occurring product called amyloid-beta builds up in the brain and causes these memory problems. Studies show simvastatin may possibly slow this down, and delay the start of memory problems. Down syndrome is caused by having extra genetic material on chromosome 21. This extra genetic material means people with Down syndrome also have a “double dose” of the amyloid-beta that causes memory problems, as it is also coded on chromosome 21. There has only been one previous study on simvastatin with people with Down syndrome. It looked at the medications they had taken in the past, and found the people who did not have memory problems were more likely to have taken simvastatin than those who had memory problems. So simvastatin may help prevent the chance of getting memory problems, but we do not know for sure. Doctors do not at present prescribe simvastatin to prevent dementia but do prescribe it for other conditions.

Who can participate?
Everyone with Down syndrome who will be aged 50 or more by Autumn 2012, and stays in Greater Glasgow and Clyde, Lothian, or Tayside can participate, if they do not already have dementia. GPs, learning disabilities services, and Down Syndrome Scotland are writing to people to send out invitations to take part in the study. The plan is that 60 people will take part.

What does the study involve?
A researcher will visit participants at home and ask questions about their health and supports. She/he will ask for a blood test, or a thumb pin-prick sample and saliva collection. Participants are then allocated to one of two groups. This is so we can compare the outcomes of taking simvastatin against taking a placebo (a placebo is a capsule with no medication in it.) To try to make sure the groups are the same to start with, each person is put into a group by chance (a bit like tossing a coin). There is an equal chance of getting into either of the two groups. For the following year, the doctor will prescribe people in one group a simvastatin capsule every night (40mg), and the other group a placebo capsule every night. Both groups also continue to receive all their health care and supports as per usual. Six to 12 weeks after starting, we will visit to make sure there are no side effects. After a year of taking the medication, the researcher will visit again to ask about health and supports, and request an optional blood test. We can then check the differences between the two groups. The study will assess how many people take part, and factors affecting participation. It will determine the most sensitive tests and puzzles to detect early memory changes. Differences between the two groups in memory changes over a year will be measured, to gauge the number who should be recruited in the future large study. A sub-study will also seek the views of about 10 people regarding taking part in the trial. We will also ask participants if we may store their blood samples for future use, and link to their health records in future.

What are the possible benefits and risks of taking part?
We cannot promise the study will prevent participants from developing memory problems/Alzheimer’s disease. However the study will provide important information necessary for a much larger study on simvastatin. If simvastatin does reduce the chance of getting Alzheimer disease, then half of the study participants would have benefited, and the other half will benefit from its future use, and this will also be important news for everyone with Down syndrome. We hope that people will enjoy taking part in the study and meeting with the researcher. Participants have to take a simvastatin or placebo capsule every night for a year, and avoid drinking grapefruit juice and excessive alcohol. Placebo has no risks. All medications whether given by a doctor or bought over the counter can cause side-effects in some people, and simvastatin is not an exception. It is however commonly used, so we know its safety profile is good. We have no reason to think this will be any different for people with Down syndrome, but will check. Lots of people take simvastatin to prevent heart attacks and strokes. Most people do not get side-effects. The most common side effect is muscle pain or weakness, which affects about 1 in every 100 people; occasionally people have to stop the simvastatin to get rid of this.

Where is the study run from?
The study is run from the Institute of Health and Wellbeing at the University of Glasgow (UK)

When is the study starting and how long is it expected to run for?
The study is starting at the beginning of 2012 and will run for 24 months. We plan to recruit participants until Autumn 2012.

Who is funding the study
The Chief Scientist Office, Scottish Health Department of the Scottish Government (UK)

Who is the main contact person?
Prof. Sally-Ann Cooper
Sally-Ann.Cooper@glasgow.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• Scotland
• United Kingdom

Study participating centre

Sponsor information

NHS Greater Glasgow and Clyde (UK)
Government

1st Floor
R&D Central Office
The Tennent Institute
Western Infirmary
38 Church Street
Glasgow
G11 6NT
United Kingdom

Phone	+44 (0)141 211 6208
Email	Erica.Packard@ggc.scot.nhs.uk
"ROR"	https://ror.org/05kdz4d87

Funders

Funder type

Government

Results and Publications

Study outputs

Editorial Notes

01/08/2016: Publication reference added.

22/05/2012: the following changes have been made on the trial record:
1. The overall trial start date was changed from 01/01/2012 to 01/04/2012.
2. The overall trial end date was changed from 31/12/2013 to 31/03/2014.