Effect of Tadalafil on Cerebral Large Arteries in Stroke

NCT02801032 | Completed Phase 2 DMC

• 2 other identifiers: H-160208362016-000896-26
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In a double blind placebo-controlled cross-over study the effect of tadalafil on blood flow velocity in the large arteries of the brain, cortical brain oxygenation, peripheral endothelial function, and endothelial biomarkers will be tested in patients with lacunar stroke caused by cerebral small vessel disease.

Conditions

Stroke, Lacunar; Cerebral Small Vessel Diseases

Outcome Measures

Primary Outcomes (2)

• Difference in Blood flow velocity change in middel cerebral artery (MCA) between placebo and tadalafil

  Change in Blood flow velocity in middel cerebral artery (MCA) will be measured with transcranial doppler (TCD) before and up to three hours after intake of tadalafil/placebo.

  Measurement before and up to three hours after intake of tadalafil/placebo.

• Difference in cortical brain oxygenation between placebo and tadalafil

  Cortical brain oxygenation will be measured with near-infrared spectroscopy (NIRS) before and up to three hours after intake of tadalafil/placebo.

  Measurement before and up to three hours after intake of tadalafil/placebo.

Secondary Outcomes (2)

• Changes in endothelial response

  Measurement before and three hours after intake of tadalafil/placebo.

• Changes in endothelial biomarkers in blood

  Blood samples before and 3,5-4 hours after intake of tadalafil/placebo.

Study Arms (2)

Active Treatment

ACTIVE COMPARATOR

Tadalafil 20 mg Capsule. MRI of cerebrum pre dose. Transcranial Doppler, near-infrared spectroscopy (NIRS), endothelial response with EndoPAT2000, and endothelial biomarkers (pre and post dose).

Drug: Tadalafil

Control

PLACEBO COMPARATOR

Placebo Capsule. MRI of cerebrum pre dose. Transcranial Doppler, near-infrared spectroscopy (NIRS), endothelial response with EndoPAT2000, and endothelial biomarkers (pre and post dose).

Drug: Placebo

Interventions

Tadalafil DRUG

Single dose, 20 mg capsule p.o. minimum one week apart from placebo. MRI of cerebrum before the first trial day. Transcranial Doppler to measure blood flow velocity in MCA bilaterally before and after intervention. Near-infrared spectroscopy (NIRS) to measure cortical brain oxygenation before and after intervention. EndoPAT2000 to estimate endothelial function before and after intervention. Endothelial biomarkers in blood samples before and after intervention.

Also known as: Cialis

Active Treatment

Placebo DRUG

Single dose, matching capsule p.o. minimum one week apart from active treatment. MRI of cerebrum before the first trial day. Transcranial Doppler to measure blood flow velocity in MCA bilaterally before and after intervention. Near-infrared spectroscopy (NIRS) to measure cortical brain oxygenation before and after intervention. EndoPAT2000 to estimate endothelial function before and after intervention. Endothelial biomarkers in blood samples before and after intervention.

Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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 5 months previously; OR
• transient ischemic attack (TIA) lasting \< 24 hours with limb weakness, hemi-sensory loss or dysarthria at least 5 months previously AND with MR DWI performed acutely showing lacunar infarction, OR if MRI is not performed within ten days of TIA, a lacunar infarction in an anatomically appropriate position is demonstrated on a subsequent MRI.
• Age ≥ 50 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
• Pregnancy or nursing
• Cortical infarction (\>1.5 cm maximum diameter)
• Systolic BP \< 90 and/or diastolic BP \< 50
• eGFR \< 30 ml/min/1,73m2
• Severe hepatic impairment
• History of Lactose intolerance
• Concomitant use of PDE5 inhibitors e.g. sildenafil, tadalafil, vardenafil
• Patients receiving nicorandil and nitrates e.g. isosorbide mononitrate, isosorbide dinitrate, glyceryl trinitrate
• Body weight \> 130kg
• Uncontrolled cardiac failure
• Persistent or paroxysmal atrial fibrillation
• History of "sick sinus syndrome" or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block
• Uncontrolled COPD
• Stroke or TIA within the last 5 months.

Sponsors & Collaborators

• Christina Kruuse: lead

Study Sites (1)

Department of Neurology, Herlev-Gentofte Hospital

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Stroke, Lacunar; Cerebral Small Vessel Diseases

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Thrombotic Stroke; Ischemic Stroke; Stroke; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Christina R Kruuse, MD, PhD

  Consultant Neurologist, Dept Neurology, Herlev Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, DMSc, Consultant Neurologist, Associate Professor

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 15, 2016
• Study Start: November 29, 2016
• Primary Completion: August 4, 2017
• Study Completion: August 4, 2017
• Last Updated: August 22, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)