NCT02450253

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
55

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Sep 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 18, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 21, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 25, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 25, 2018

Completed
Last Updated

October 27, 2022

Status Verified

August 1, 2018

Enrollment Period

2.4 years

First QC Date

May 18, 2015

Last Update Submit

October 25, 2022

Conditions

Dementia, Vascular

Keywords

Vascular cognitive impairment

Outcome Measures

Primary Outcomes (1)

  • change in deep brain blood flow as measured by MRI-Arterial Spin Labelling

    3-5 hours following IMP dosing

Secondary Outcomes (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

    3-5 hours following IMP dosing

Study Arms (2)

Active Treatment

ACTIVE COMPARATOR

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: TadalafilBehavioral: Cognitive functioning testsBehavioral: Neuropsychological testsOther: MRI Scan - Arterial Spin Labelling

Control

PLACEBO COMPARATOR

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: PlaceboBehavioral: Cognitive functioning testsBehavioral: Neuropsychological testsOther: MRI Scan - Arterial Spin Labelling

Interventions

TadalafilDRUG

single dose, 20 mg capsule p.o.

Also known as: Cialis
Active Treatment
PlaceboDRUG

single dose, matching capsule p.o.

Control
Cognitive functioning testsBEHAVIORAL

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

Also known as: TOPF, NIHSS, MoCA,
Active TreatmentControl
Neuropsychological testsBEHAVIORAL

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

Also known as: CANTAB, BMIPB, RBANS subtest
Active TreatmentControl
MRI Scan - Arterial Spin LabellingOTHER

Pre and post IMP dose on 2 occasions to detect difference in blood flow in deep brain 4 MRI scans in total

Active TreatmentControl

Eligibility Criteria

Age55 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \. 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)
  • \. Clinical evidence of cerebral small vessel disease can be:
  • lacunar stroke syndrome with symptoms lasting \>24 hours, occurring at least 6 months previously; OR:
  • 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
  • \. Age ≥ 55 years.
  • \. 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

You may not qualify if:

  • Known diagnosis of dementia
  • Cortical infarction (\>1.5 cm maximum diameter)
  • Systolic BP \<90 and/or diastolic BP \< 50
  • Creatinine Clearance\<50ml/min
  • Severe hepatic impairment
  • History of Lactose intolerance
  • Concomitant use of PDE5 inhibitors e.g. sildenafil, tadalafil, vardenafil.
  • Concomitant use of alpha-blockers e.g. alfuzosin, doxazosin, indoramin, prazosin, tamsulosin, and terazosin can all increase the risk of postural hypotension.
  • Participants receiving nicorandil and nitrates e.g. isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate
  • weight \> 130kg
  • Uncontrolled cardiac failure
  • \. Persistent or paroxysmal atrial fibrillation
  • \. History of gastric ulceration
  • \. History of 'sick sinus syndrome' or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block
  • \. Uncontrolled COPD
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

St George's Healthcare NHS Trust

London, SW17 0QT, United Kingdom

Location

Related Publications (2)

  • Pauls MMH, Binnie LR, Benjamin P, Betteridge S, Clarke B, Dhillon MK, Ghatala R, Hainsworth FAH, Howe FA, Khan U, Kruuse C, Madigan JB, Moynihan B, Patel B, Pereira AC, Rostrup E, Shtaya ABY, Spilling CA, Trippier S, Williams R, Young R, Barrick TR, Isaacs JD, Hainsworth AH. The PASTIS trial: Testing tadalafil for possible use in vascular cognitive impairment. Alzheimers Dement. 2022 Dec;18(12):2393-2402. doi: 10.1002/alz.12559. Epub 2022 Feb 8.

    PMID: 35135037DERIVED

  • Binnie LR, Pauls MMH, Benjamin P, Dhillon MK, Betteridge S, Clarke B, Ghatala R, Hainsworth FAH, Howe FA, Khan U, Kruuse C, Madigan JB, Moynihan B, Patel B, Pereira AC, Rostrup E, Shtaya ABY, Spilling CA, Trippier S, Williams R, Isaacs JD, Barrick TR, Hainsworth AH. Test-retest reliability of arterial spin labelling for cerebral blood flow in older adults with small vessel disease. Transl Stroke Res. 2022 Aug;13(4):583-594. doi: 10.1007/s12975-021-00983-5. Epub 2022 Jan 26.

    PMID: 35080734DERIVED

MeSH Terms

Conditions

Dementia, Vascular

Interventions

TadalafilNeuropsychological Tests

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesIntracranial ArteriosclerosisIntracranial Arterial DiseasesDementiaLeukoencephalopathiesArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CarbolinesPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIndole AlkaloidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds, 3-RingPsychological TestsBehavioral Disciplines and Activities

Study Officials

  • Jeremy Dr Isaacs, MRCP PhD

    St George's University Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 18, 2015

First Posted

May 21, 2015

Study Start

September 1, 2015

Primary Completion

January 25, 2018

Study Completion

January 25, 2018

Last Updated

October 27, 2022

Record last verified: 2018-08

Locations

GB(1)