Preventing cognitive decline and dementia from cerebral small vessel disease
| ISRCTN | ISRCTN12580546 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12580546 |
| EudraCT/CTIS number | 2015-001953-33 |
| ClinicalTrials.gov number | NCT02481323 |
| Secondary identifying numbers | PrevSVD-2015 |
- Submission date
- 14/05/2015
- Registration date
- 05/07/2015
- Last edited
- 17/08/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English Summary
Background and study aims
About 35,000 people each year in the UK have a type of stroke, called ‘lacunar’ or ‘small vessel’ stroke, which is different to other common types of stroke and for which there is no proven treatment. There is some evidence to suggest that small vessel stroke is caused by damage to the lining of the tiny blood vessels in the brain that stops the vessels functioning normally and damages the brain. This damage not only causes stroke, but it also causes problems with thinking and walking. It is possible that damage to the small blood vessels of the brain causes up to 40% of all dementias. Some drugs that are commonly used in other blood vessel diseases may help improve vessel function and prevent worsening of small vessel damage in the brain; however, the drugs need to be tested for this condition first. One such drug yet to be tested in the UK is cilostazol, although it has been tested in the Far East, but not on dementia. Another drug widely used in the UK in heart disease but not stroke is called isosorbide mononitrate. The aim of this small study is to find out how patients feel about testing the effects of cilostazol and isosorbide mononitrate on blood vessel function. The study will use detailed scanning and blood vessel measurements, and find out if both drugs might be better than just one. The results of this study will be used to inform a future large clinical study to investigate whether these drugs prevent worsening of small vessel disease.
Who can participate?
Adults who have had a mild ischaemic stroke in the past 4 years
What does the study involve?
Participants are randomly allocated into one of four groups. Each group is given different medication - one group receives cilostazol, one receives isosorbide mononitrate, one receives both drugs to start immediately and the other group gets both drugs but delay the start for three weeks. Participants are monitored for side effects and tolerability of the medication, the safety of the medication in combination with usual post-stroke medication and the effects of the medications on measurements of how well blood vessels are working in the brain and the rest of the body. During the 10-week study period the drugs are switched, so half of the participants eventually take both of the drugs. All participants also take both of the drugs in combination at some point during the study. The measurements are repeated up to 3 times to see what effect this has.
What are the possible benefits and risks of participating?
The aim of this study is to show that these medications are safe to use in people after a stroke. The main risks are associated with the side effects of the medications, which are well known as they have been used extensively to treat other conditions. The most common side effect is a headache but this normally settles after a few days.
Where is the study run from?
1. University of Edinburgh (UK)
2. University of Nottingham (UK)
When is the study starting and how long is it expected to run for?
October 2015 to October 2017
Who is funding the study?
Alzheimer's Society (UK)
Who is the main contact?
1. Dr Julia Boyd (public)
Julia.boyd@ed.ac.uk
2. Prof J Wardlaw (scientific)
joanna.wardlaw@ed.ac.uk
Contact information
Public
Edinburgh Clinical Trials Unit
University of Edinburgh (Usher Institute)
Outpatients Building - 2nd Floor D35
Western General Hospital
Crewe Road
Edinburgh
EH4 2XU
United Kingdom
 ORCID ID |
0000-0002-9872-3893 |
|---|---|
| Phone | +44 (0)131 537 3842 |
| Julia.boyd@ed.ac.uk |
Scientific
Centre for Clinical Brain Sciences
Chancellor's Building
University of Edinburgh
49 Little France Crescent
Edinburgh
EH16 4SB
United Kingdom
| Phone | +44 (0)131 537 2943 |
|---|---|
| joanna.wardlaw@ed.ac.uk |
Study information
| Study design | Two-centre dose-escalation factorial placebo-controlled prospective blinded intermediary endpoint trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Preventing cognitive decline and dementia from cerebral Small Vessel Disease (Prevent-SVD): a phase II pilot, factorial, randomised, open label blinded end-point trial to investigate short-term effects of cilostazol and isosorbide mononitrate on tolerability, safety, and vascular function in patients with small vessel disease associated stroke. (Lacunar Intervention Trial 1 (LACI-1)) |
| Study acronym | Prevent-SVD |
| Study hypothesis | Cilostazol and ISMN will be tolerable to participants in full dose and will improve endothelial function in participants with clinically-evident SVD, as determined using cerebrovascular reactivity and systemic arterial compliance measures. |
| Ethics approval(s) | Scotland A REC, 09/11/2015, ref: 15/SS/0154 |
| Condition | Stroke due to cerebral small vessel disease |
| Intervention | Participants will be randomised to one of four groups to take one or other drug or both starting immediately or both with a delayed start, the dose of each drug initially being started at low dose and then increased per week to target dose: 1. Cilostazol 50 to 100mg twice daily 2. Isosorbide mononitrate 25mg twice daily |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 1. Cilostazol 2. Isosorbide mononitrate |
| Primary outcome measure | Number of patients reaching target dose judged on direct questioning, medication diary and tablet count |
| Secondary outcome measures | 1. Symptoms of headache, palpitations, or loose stools (all present/absent and if present then degree of interference with daily life), dizziness (dizziness scale), nausea (nausea scale) assessed every two weeks during the trial 2. Safety (bleeding, recurrent vascular events, death) assessed at the end of the trial 3. Effect on blood pressure measured three times standing and sitting with an omron bp device assessed in weeks 3 and 8 4. Effect on platelet function measured with a specialised platelet function assay (platelet solutions) assessed in weeks 3 and 8 5. Effect on cerebrovascular reactivity measured with magnetic resonance imaging and carbon dioxide breathing challenge assessed in week 8 6. Effect on arterial stiffness measured using pulse wave velocity and pulse wave analysis assessed in week 3 and week 8 |
| Overall study start date | 01/10/2015 |
| Overall study end date | 31/10/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 57 |
| Total final enrolment | 57 |
| Participant inclusion criteria | 1. Mild symptomatic ischaemic stroke compatible with a lacunar ischaemic stroke in the past four years with brain magnetic resonance imaging or CT brain scanning that confirmed the relevant infarct or excluded other cause for symptoms 2. Age >35 years 3. Independent in activities of daily living (modified Rankin ≤2) 4. Able to give consent (Montreal Cognitive Assessment score 26-30) |
| Participant exclusion criteria | 1. Other significant acute neurological illness since suffering stroke 2. Age <35 3. Requiring assistance with activities of daily living (Modified Rankin ≥3) 4. Active cardiac disease (myocardial infarction in past 6 months, active angina, symptomatic cardiac failure) 5. Carotid stenosis >50% NASCET 6. Contraindication to trial drugs 7. Current use of trial drugs 8. Unable to swallow 9. Bleeding tendency 10. Unlikely to comply with trial medication 11. Planned surgery during the trial period 12. History of intracranial haemorrhage 13. Other life threatening illness 14. History of drug overdose or attempted suicide or significant active mental illness 15. Pregnancy |
| Recruitment start date | 01/11/2015 |
| Recruitment end date | 31/08/2017 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Western General Hospital
Edinburgh & The Royal Infirmary of Edinburgh
Edinburgh
EH16 4SA
United Kingdom
Nottingham
NG7 2RD
United Kingdom
Sponsor information
University/education
Research & Development Management Suite
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 242 9262 |
|---|---|
| ray.french@ed.ac.uk | |
| Website | http://www.accord.ed.ac.uk/contactus/ |
"ROR" |
https://ror.org/01nrxwf90 |
Hospital/treatment centre
Research & Development Management Suite
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 242 6515 |
|---|---|
| d.e.newby@ed.ac.uk | |
| Website | http://www.accord.ed.ac.uk/contactus/ |
|
"ROR" |
https://ror.org/03q82t418 |
Funders
Funder type
Charity
Private sector organisation / Associations and societies (private and public)
- Alternative name(s)
- alzheimerssoc
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/05/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Presentation at European Stroke Organisation Conference (ESOC) and publication in peer-reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Joanna Wardlaw (joanna.wardlaw@ed.ac.uk). |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol and statistical analysis plan | 01/07/2018 | Yes | No | |
| Results article | results | 01/05/2019 | 25/06/2019 | Yes | No |
| Results article | safety data results | 03/07/2019 | 25/07/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 01/12/2021 | 17/08/2023 | Yes | No |
Editorial Notes
17/08/2023: Publication reference added.
25/07/2019: Publication reference added.
25/06/2019: Publication reference and total final enrolment number added.
15/01/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/10/2017 to 31/08/2017.
2. The overall trial end date was changed from 01/10/2017 to 31/10/2017.
3. The intention to publish date was changed from 01/10/2017 to 01/05/2019.
4. The target number of participants was changed from 60 to 57.
5. The IPD sharing statement was added.
15/09/2017: Publication reference added.
31/08/2016: Ms Kirsten Shuler has been removed as a study contact and Dr Julia Boyd has been added.
29/03/2016: Ethics approval information added.
