Lumacaftor Yields Reversal of Impaired Cerebral Blood Flow in Heart Failure Patients
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorQanatpharma AG
About this trial
Cognitive impairment (CI) is highly prevalent in patients with heart failure with reduced ejection fraction (HFrEF), which has significant implications for disease management, quality of life and clinical outcomes. Currently, there are no specific treatments for CI aside from the current standard of care therapy for HF, making this a high unmet medical need. Impaired cerebral autoregulation is a proposed mechanistic factor that leads to cerebral hypoperfusion, ischemic damage and the development for CI. Preclinical data indicates that restoring CFTR-protein expression normalizes cerebral microvascular function and cerebral blood flow (CBF) in models of HF. The purpose of this study is to investigate whether CFTR-targeting therapy enhances cerebral perfusion and cognitive function in heart failure patients using the CFTR-corrector Lumacaftor.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provide written informed consent
Aged 18 years or older with stable heart failure NYHA class II-III, with reduced cardiac output and an EF of <40% on optimal goal directed medical therapy as per CCS Guidelines and the AHA/ACC/HFSA Guidelines for the Management of Heart Failure
No hospital admissions for inpatient care in 3 months prior to study
CBF at screening of ≤45 mL/100g/min
Disqualifiers
Participants with symptomatic HF who have non-MRI compatible cardiac implantable electronic devices (CIEDs), such as a cardiac defibrillator or pacemaker, or in whom this is required within 3 months of the study
Those requiring coronary revascularisation in 6 months following the study
Participants with cystic fibrosis (CF) or any other condition that may require use of CFTR modulating agents
Participants using antiallergics (e.g., montelukast), antibiotics (e.g., clarithromycin), anticoagulants (e.g., warfarin), anticonvulsants (e.g., carbamazepine), antidepressants (e.g., citalopram), antifungals (e.g., fluconazole), anti-mycobacterials (e.g., rifabutin), barbituates, benzodiazepines (e.g., midazolam), immunosuppressants (e.g., cyclosporine), proton pump inhibitors (e.g., esomeprazole) within 30 days of trial start
Trial design
Design model
Parallel
Treatments tested in this trial
Lumacaftor 200 MG
DrugLumacaftor 200 mg q12
Placebo
DrugIdentical placebo
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: LumacaftorExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Efficacy of lumacaftor treatment in increasing cerebral blood flow versus placebo in HFrEF patients.
Change from baseline in global cerebral blood flow at 1 month using treatment or placebo as assessed by perfusion weighted MRI.
Time frame
Baseline and 1 monthSecondary outcomes
1
Rate of treatment-emergent adverse events as assessed by MedDRA.
Number of treatment-emergent AEs by severity and treatment received. This will capture participants who received at least one dose of treatment.
Time frame
Baseline up to Day 902
Number of participants with clinically significant changes from baseline in physical examinations findings at 1 week, 1 month and 3 months.
Time frame
Baseline, 1 week, 1 month and 3 months3
Number of participants with clinically significant changes from baseline in vital signs at 1 week, 1 month and 3 months.
Time frame
Baseline, 1 week, 1 month and 3 months4
Number of participants with clinically significant changes from baseline in electrocardiograms (ECGs) at 1 week, 1 month and 3 months.
Time frame
Baseline, 1 week, 1 month and 3 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Qanatpharma AG
Lead sponsor
Qanatpharma Canada LTD
Collaborator
Source ClinicalTrials.gov