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Cerebral Small Vessel DiseasesPhase 2Prevent-SVDNCT02481323

Lacunar Intervention Trial 1 (LACI-1)

A Phase 2 study testing isosorbide mononitrate and cilostazol in people with Cerebral Small Vessel Diseases and Cognitive Impairment, run by University of Edinburgh at 2 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase II pilot randomised, factorial, short term dose escalation, open label, blinded intermediary endpoint trial, in two hospital centres in the UK, of tolerability and safety of cilostazol, isosorbide mononitrate, both or neither in patients with small vessel disease manifest as symptomatic small subcortical stroke. Read more about this study

Who is it for?
Ages 35 years and older
What is being tested?
isosorbide mononitrate and cilostazol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
2 sitesUnited Kingdom
Study dates
Mar 2016to 30 Nov 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Mild symptomatic ischaemic stroke in the past four years compatible with a clinical lacunar stroke syndrome, with brain magnetic resonance imaging or computed tomography scanning that is compatible with a symptomatic small subcortical (lacunar) infarct, or if no recent relevant infarct is visible, that excluded other cause for symptoms
  • Age > 35 years
  • Independent in activities of daily living (modified Rankin ≤2)
  • Able to give consent themselves

Who cannot join

  • Other significant active neurological illness present since suffering stroke (eg seizures, multiple sclerosis, brain tumour)
  • Age < 35
  • Montreal Cognitive Assessment score <26
  • Requiring assistance with activities of daily living (Modified Rankin ≥3)
  • Active cardiac disease (atrial fibrillation, myocardial infarction in past 6 months, active angina, symptomatic cardiac failure)
  • Carotid stenosis > 50% in the symptomatic artery territory requiring carotid endarterectomy (prior and apparently successful carotid endarterectomy is not an exclusion criterion)
Show all 16Show fewer
  • Definite indication for, or definite contraindication to either trial drug
  • Unable to swallow
  • Bleeding tendency (platelets<100, taking anticoagulant medication)
  • Unlikely to comply with trial medication
  • Planned surgery during the trial period
  • History of intracranial haemorrhage (subdural haematoma, subarachnoid haemorrhage, intracerebral haemorrhage, but not asymptomatic haemorrhagic transformation of infarction)
  • Other life threatening illness
  • History of drug overdose or attempted suicide or significant active mental illness
  • Pregnancy
  • If recruited in Edinburgh and participating in cerebrovascular reactivity arm of trial: active respiratory illness (such as moderate to severe asthma or chronic obstructive airways disease), unable to tolerate magnetic resonance imaging or unable to lie flat

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • University of Edinburgh

    Edinburgh, EH4 2XU

  • University of Nottingham

    Nottingham, NG7 2RD

Other trials in United Kingdom

About this study

Official title: Preventing Cognitive Decline and Dementia From Cerebral Small Vessel Disease

Phase II pilot randomised, factorial, short term dose escalation, open label, blinded intermediary endpoint trial, in two hospital centres in the UK, of tolerability and safety of cilostazol, isosorbide mononitrate, both or neither in patients with small vessel disease manifest as symptomatic small subcortical stroke.

Read the detailed description

A quarter of all ischaemic strokes are lacunar (small vessel) in type, about 35000 per annum in the United Kingdom, and due to an intrinsic, non-atheromatous, non-cardioembolic perforating cerebral arteriolar disease. 'Small vessel disease' also affects the brain diffusely, causing up to 40% of dementias, alone or mixed with Alzheimer's disease, 350,000+ patients estimated currently in the United Kingdom. There is no proven treatment: conventional antiplatelet drugs may be ineffective or even hazardous, antihypertensive treatment and statins have been disappointing. The disease mechanism is poorly understood but endothelial dysfunction, blood-brain barrier failure and vessel stiffness appear to contribute to the pathogenesis. Promising data available for licensed drugs with relevant modes of action, cilostazol (>6000 stroke patients in the Asia Pacific region) and isosorbide mononitrate (ISMN, widely used in cardiac disease) support their testing in small vessel disease. This trial will be a phase 2, randomised, dose-escalation, factorial trial to test short-term administration of cilostazol, Isosorbide Mononitrate, both, or neither, to provide data on patient tolerability of dose (including headache, dizziness), safety (including blood pressure, platelet function), provide mechanistic evidence of efficacy (cerebrovascular reactivity, arterial compliance), and to inform the design of a larger phase 2-3 trial. The trial will recruit 60 patients with small vessel disease, in two expert stroke centres (Edinburgh and Nottingham) where there are suitable patients, expert stroke centres, established trials infrastructures and neuroimaging and platelet testing expertise. The trial will also advance methods to stratify patients by small vessel disease burden in routine practise and data on intermediary mechanistic outcomes to assist in planning future trials testing novel agents for either stroke or dementia.

Being tested
isosorbide mononitrate, cilostazol
Keywords
cerebral small vessel disease, cerebrovascular reactivity, cilostazol, isosorbide mononitrate
Medical subject headings
Cerebral Small Vessel Diseases, Cognitive Dysfunction, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • isosorbide mononitrateDrug

    Also called Isotard

    slow release nitric oxide donor that enhances vasodilation and widely used in angina prophyaxis

  • cilostazolDrug

    Also called pletal

    phosphodiesterase 3-inhibitor that enhances vessel wall function with weak antiplatelet effects

Study groups in NCT02481323
Study groupRoleWhat they receive
Group 1Active comparatorIsosorbide mononitrate 25mg bd
Receives: Drug: isosorbide mononitrate
Group 2Active comparatorCilostazol 100mg bd
Receives: Drug: cilostazol
Group 3Active comparatorIsosorbide mononitrate 25mg bd and cilostazol 100mg bd start immediately
Receives: Drug: isosorbide mononitrate; Drug: cilostazol
Group 4OtherIsosorbide mononitrate 25mg bd and cilostazol 100mg bd delayed start
Receives: Drug: isosorbide mononitrate; Drug: cilostazol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tolerability proportion of patients able to tolerate the target dose

    proportion of patients able to tolerate the target dose

    Measured: 8 weeks

Secondary outcomes (13)

  1. Safety - bleeding

    systemic or intracranial bleeding

    Measured: 12 weeks

  2. Safety - recurrent stroke

    recurrent vascular events,

    Measured: 12 weeks

  3. Safety - death

    death

    Measured: 12 weeks

  4. Safety - blood pressure

    reduction in blood pressure

    Measured: 8 weeks

  5. Safety - bleeding

    effect on platelet function assessed using p-selectin

    Measured: 8 weeks

  6. Efficacy - cerebrovascular function

    effect on cerebrovascular reactivity assessed using carbon dioxide challenge in magnetic resonance imaging

    Measured: 8 weeks

  7. Efficacy - systemic arterial stiffness

    effect on systemic large artery stiffness assessed with pulse wave velocity measurement

    Measured: 8 weeks

  8. Tolerability Proportion of patients with headache that interferes with daily activities

    Proportion of patients with headache that interferes with daily activities

    Measured: 8 weeks

  9. Tolerability Proportion of patients with dizziness that interferes with daily activities

    Proportion of patients with dizziness that interferes with daily activities

    Measured: 8 weeks

  10. Tolerability Proportion of patients with nausea that interferes with daily activities

    Proportion of patients with nausea that interferes with daily activities

    Measured: 8 weeks

  11. Tolerability Proportion of patients with palpitations

    Proportion of patients with palpitations

    Measured: 8 weeks

  12. Tolerability Proportion of patients with loose stools

    Proportion of patients with loose stools

    Measured: 8 weeks

  13. Tolerability Tablet count

    Tablet count

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2015 (estimated)
  2. Study startMar 2016
  3. Primary completionAug 2017
  4. Study completion30 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02481323
Sponsor's protocol ID
PrevSVD-2015
Other IDs
2015-001953-33, 252 (AS-PG-14-033), 2015
Acronym
Prevent-SVD
Status last verified
Jan 2018
First submitted
19 Jun 2015
Last updated
19 Jan 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Blair GW, Janssen E, Stringer MS, Thrippleton MJ, Chappell F, Shi Y, Hamilton I, Flaherty K, Appleton JP, Doubal FN, Bath PM, Wardlaw JM. Effects of Cilostazol and Isosorbide Mononitrate on Cerebral Hemodynamics in the LACI-1 Randomized Controlled Trial. Stroke. 2022 Jan;53(1):29-33. doi: 10.1161/STROKEAHA.121.034866. Epub 2021 Dec 1.

    PubMed 34847709

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing isosorbide mononitrate and cilostazol in people with Cerebral Small Vessel Diseases and Cognitive Impairment, run by University of Edinburgh at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerability proportion of patients able to tolerate the target dose (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02481323, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2018; AzTrials last refreshed its copy on 31 Oct 2026.

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