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Perfusion by Arterial Spin Labelling Following Single Dose Tadalafil in Small Vessel Disease (PASTIS) Trial (PASTIS)

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ClinicalTrials.gov Identifier: NCT02450253
Recruitment Status : Active, not recruiting
First Posted : May 21, 2015
Last Update Posted : August 21, 2018
Sponsor:
Collaborators:
Alzheimer’s Drug Discovery Foundation
Alzheimer's Society UK
University of Copenhagen
University of Glasgow
St George's University Hospitals NHS Foundation Trust
Information provided by (Responsible Party):
St George's, University of London

Brief Summary:
Could Tadalafil improve blood flow in deep brain tissue and potentially improve cognitive function in patients with cerebral small vessel disease

Condition or disease Intervention/treatment Phase
Dementia, Vascular Drug: Tadalafil Drug: Placebo Behavioral: Cognitive functioning tests Behavioral: Neuropsychological tests Other: MRI Scan - Arterial Spin Labelling Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Perfusion by Arterial Spin Labelling Following Single Dose Tadalafil in Small Vessel Disease (PASTIS) Trial
Study Start Date : September 2015
Actual Primary Completion Date : January 25, 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Tadalafil

Arm Intervention/treatment
Active Comparator: Active Treatment
Tadalafil 20mg Capsule Stat single dose 2 x MRI scans (pre and post dose) Neuropsychological tests pre and post IMP dose Cognitive functioning prior to 1st MRI scan of that visit
Drug: Tadalafil
single dose, 20 mg capsule p.o.
Other Name: Cialis

Behavioral: Cognitive functioning tests
Cognitive function tests will be performed prior to MRI scan 1 performed prior to IMP dosing on 2 occasions as patient will act as their own control
Other Name: TOPF, NIHSS, MoCA,

Behavioral: Neuropsychological tests

Neuropsychological tests will be performed prior to pre IMP dose MRI scan & then parallel V2 of the tests repeated 3-5 post IMP dose and before 2nd MRI scan.

Participants act as own controls as 1 IMP occasion will be placebo- 2nd IMP occasion will be active. 7-30 days apart

Other Name: CANTAB, BMIPB, RBANS subtest

Other: MRI Scan - Arterial Spin Labelling
Pre and post IMP dose on 2 occasions to detect difference in blood flow in deep brain 4 MRI scans in total

Placebo Comparator: Control
Matched placebo Capsule Stat single dose 2 x MRI scans (pre and post dose) Neuropsychological tests pre and post IMP dose Cognitive functioning prior to 1st MRI scan of that visit
Drug: Placebo
single dose, matching capsule p.o.

Behavioral: Cognitive functioning tests
Cognitive function tests will be performed prior to MRI scan 1 performed prior to IMP dosing on 2 occasions as patient will act as their own control
Other Name: TOPF, NIHSS, MoCA,

Behavioral: Neuropsychological tests

Neuropsychological tests will be performed prior to pre IMP dose MRI scan & then parallel V2 of the tests repeated 3-5 post IMP dose and before 2nd MRI scan.

Participants act as own controls as 1 IMP occasion will be placebo- 2nd IMP occasion will be active. 7-30 days apart

Other Name: CANTAB, BMIPB, RBANS subtest

Other: MRI Scan - Arterial Spin Labelling
Pre and post IMP dose on 2 occasions to detect difference in blood flow in deep brain 4 MRI scans in total




Primary Outcome Measures :
  1. change in deep brain blood flow as measured by MRI-Arterial Spin Labelling [ Time Frame: 3-5 hours following IMP dosing ]

Secondary Outcome Measures :
  1. Change in regional CBF in cortical grey matter areas Plasma [drug concentration] dependence of deep CBF as measured by MRI ASL Changes in neuropsychological parameters including attention in Neuro attention and cognitive speed [ Time Frame: 3-5 hours following IMP dosing ]


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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Radiological evidence of cerebral small vessel disease defined as: MRI evidence of lacunar infarct(s) (≤ 1.5 cm maximum diameter) and/or confluent deep white matter leukoaraiosis (≥ grade 2 on Fazekas scale)

2. Clinical evidence of cerebral small vessel disease can be:

  1. lacunar stroke syndrome with symptoms lasting >24 hours, occurring at least 6 months previously; OR:
  2. transient ischaemic attack lasting < 24 hours with limb weakness, hemi-sensory loss or dysarthria at least 6 months previously AND with MRI DWI performed acutely showing lacunar infarction, OR if MRI is not performed within 10 days of TIA, a lacunar infarction in an anatomically appropriate position is demonstrated on a subsequent MRI

    3. Age ≥ 55 years.

    4. Imaging of the carotid arteries with Doppler ultrasound, CT angiography or MR angiography in the previous 12 months, demonstrating < 70% stenosis in both internal carotid arteries

    Exclusion Criteria:

    1. Known diagnosis of dementia
    2. Cortical infarction (>1.5 cm maximum diameter)
    3. Systolic BP <90 and/or diastolic BP < 50
    4. Creatinine Clearance<50ml/min
    5. Severe hepatic impairment
    6. History of Lactose intolerance
    7. Concomitant use of PDE5 inhibitors e.g. sildenafil, tadalafil, vardenafil.
    8. Concomitant use of alpha-blockers e.g. alfuzosin, doxazosin, indoramin, prazosin, tamsulosin, and terazosin can all increase the risk of postural hypotension.
    9. Participants receiving nicorandil and nitrates e.g. isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate
    10. weight > 130kg

    11 Uncontrolled cardiac failure

    12. Persistent or paroxysmal atrial fibrillation

    13. History of gastric ulceration

    14. History of 'sick sinus syndrome' or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block

    15. Uncontrolled COPD

    16. Stroke or TIA within the last 6 months

    17. MRI not tolerated or contra-indicated : MRI exclusion criteria -Participant has a cardiac pacemaker; recent surgery; vascular clips; metal implants or joint replacements; have had metal fragments in their eyes; has ever worked on a lathe; has shrapnel from a war injury; possibility of pregnancy

    18. Known monogenic causes of stroke e.g.. CADASIL

    19 Unable to provide informed consent

    20. enrolled in another CTIMP study


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02450253


Locations
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United Kingdom
St George's Healthcare NHS Trust
London, United Kingdom, SW17 0QT
Sponsors and Collaborators
St George's, University of London
Alzheimer’s Drug Discovery Foundation
Alzheimer's Society UK
University of Copenhagen
University of Glasgow
St George's University Hospitals NHS Foundation Trust
Investigators
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Principal Investigator: Jeremy Dr Isaacs, MRCP PhD St George's University Hospitals NHS Foundation Trust

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Responsible Party: St George's, University of London
ClinicalTrials.gov Identifier: NCT02450253     History of Changes
Other Study ID Numbers: 14.0189
2015-001235-20 ( EudraCT Number )
15/LO/0714 ( Other Identifier: Research Ethics Committee (REC) )
20140901 ( Other Grant/Funding Number: ADDF )
First Posted: May 21, 2015    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: August 2018
Keywords provided by St George's, University of London:
Vascular cognitive impairment
Additional relevant MeSH terms:
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Dementia, Vascular
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Tadalafil
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents