Clinical trial NCT05890534: Pycnogenol® in Post-COVID-19 Condition
Official title: Pycnogenol® in People With Post-COVID-19 Condition: a Quadruple-blind, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Post COVID-19 Condition
Long COVID
Keywords: COVID-19
post COVID symptoms
Pycnogenol®
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2023-06-06
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the effect of Pycnogenol® versus placebo on patient-reported health status in people with post COVID-19 condition.

Detailed description: The primary aim of this 12-week quadruple blind, single-center randomized controlled trial is to determine the effect of Pycnogenol® (200mg daily) versus placebo on patient-reported health status (EQ-Visual Analogue Scale) in people with post COVID-19 condition. Secondary outcomes include symptoms, fatigue, cognitive function, health-related quality of life, functional exercise capacity and blood biomarkers of inflammation, endothelial function and oxidative stress.

Pycnogenol® is a licensed pine tree bark extract (Pinus pinaster ssp. atlantica) and primarly used for the treatment of venous disorders. Various studies reported beneficial effects in other conditions such as diabetes, metabolic syndrome and cardiovascular disorders. Pycnogenol® exerts antioxidative, anti-inflammatory and antiproliferative effects and has been shown to improve vascular endothelial function. Pycnogenol® may have potential to improve the health status of people suffering from post COVID-19 condition.

This trial lasts for 12 weeks. Participants are invited to visit the study center four times: screening visit, baseline visit, follow-up 1 visit (6 weeks after baseline visit), follow-up 2 visit (12 weeks after baseline visit).

In a substudy using baseline data, the investigators plan to study associations between objectively measured physical activity, severity of post COVID-19 condition, symptom burden and severity (e.g., fatigue, dyspnoea), functional exercise capacity, and health-related quality of life.

Eligibility criteria: Inclusion Criteria:

* SARS-CoV-2 infection confirmed by positive PCR or rapid antigen test for professional use or written medical report
* Post-COVID condition (WHO definition), i.e., ≥ 3 months after SARS-CoV2 infection and ongoing or recurring symptoms for at least 2 months that cannot be explained by alternative diagnosis
* Symptoms include fatigue and / or cognitive impairment ("brain fog") and / or dyspnea and / or post-exertional malaise
* Willing to participate and having signed informed consent
* Sufficient language and cognitive skills
* Ability to participate in study visits
* No foreseeable change in medication

Exclusion Criteria:

* Severe comorbidities such as liver or renal failure, advanced COPD or pulmonary fibrosis requiring \> 5L oxygen/min at rest, active malignancy, advanced heart failure, cardio-vascular events within the previous 24 weeks (such as unstable coronary artery disease, coronary revascularization, myocardial infarction, stroke, transient ischemic attack, critical limb ischemia, pulmonary embolism, deep vein thrombosis), uncontrolled severe hypertension, uncontrolled diabetes uncontrolled autoimmune or inflammatory disease (the responsible study physician will decide each case on an individual basis)
* Acute respiratory or other infections (postpone baseline visit until resolved)
* Clinical diagnosis of a psychiatric disease (e.g., depression, anxiety disorder, schizophrenia) that is untreated and/or unstable (the responsible study physician will decide each case on an individual basis)
* COVID-19 vaccination less than 4 weeks prior to the baseline visit (i.e., first or second dose of a two-dose vaccination regimen, first dose of a single dose vaccination regimen, booster) or during study participation (booster shot will be offered at screening visit, wait time until baseline visit 4 weeks)
* Known intolerance of the study drug
* Regular intake of Pycnogenol®
* Pregnancy or lactating. For women and transgender individuals of childbearing age, who can anamnestically not exclude a pregnancy, are offered a pregnancy test during the study visits.
* Being enrolled in another interventional study that may interfere with the current study (the responsible study physician will decide each case on an individual basis)

Primary outcomes:
measure: Health status (EQ-VAS)
timeFrame: Change from baseline to 12 weeks
Secondary outcomes:
measure: Post COVID-19 symptoms
timeFrame: Change from baseline to 12 weeks
measure: Fatigue
timeFrame: Change from baseline to 12 weeks
measure: Dyspnea
timeFrame: Change from baseline to 12 weeks
measure: Cognitive function
timeFrame: Change from baseline to 12 weeks
measure: Anxiety and depression
timeFrame: Change from baseline to 12 weeks
measure: Health-related quality of life (EQ-5D-5L)
timeFrame: Change from baseline to 12 weeks
measure: Functional exercise capacity
timeFrame: Change from baseline to 12 weeks
measure: Physical activity
timeFrame: Change from baseline to 12 weeks
measure: Soluble Thrombomodulin (sTM)
timeFrame: Change from baseline to 12 weeks
measure: von Willebrand Factor antigen (VWF:Ag)
timeFrame: Change from baseline to 12 weeks
measure: Syndecan-1
timeFrame: Change from baseline to 12 weeks
measure: Circulating Cascular Cell Adhesion Molecule-1 (sVCAM 1)
timeFrame: Change from baseline to 12 weeks
measure: C-reative protein (CRP)
timeFrame: Change from baseline to 12 weeks
measure: Interleukine 6 (IL 6)
timeFrame: Change from baseline to 12 weeks
measure: sCD40L
timeFrame: Change from baseline to 12 weeks
measure: sP selectin
timeFrame: Change from baseline to 12 weeks
measure: D-Dimer
timeFrame: Change from baseline to 12 weeks
measure: Activated partial thromboplastin time (aPTT)
timeFrame: Change from baseline to 12 weeks
measure: International normalized ratio (INR) blood test
timeFrame: Change from baseline to 12 weeks
measure: Total antioxidant capacity (TAC)
timeFrame: Change from baseline to 12 weeks
measure: Aspartate aminotransferase (ASAT)
timeFrame: Change from baseline to 12 weeks
measure: Alanine aminotransferase (ALAT)
timeFrame: Change from baseline to 12 weeks
measure: Gamma glutamyltransferase (γ-GT)
timeFrame: Change from baseline to 12 weeks
measure: Creatinine
timeFrame: Change from baseline to 12 weeks
Other outcomes:
measure: Adherence to study products
timeFrame: Baseline to 12 weeks
measure: Post-exertional malaise
timeFrame: Baseline to 12 weeks
Locations:
city: Zürich
country: Switzerland
facility: University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Department of Public & Global Health
Study officials:
affiliation: University of Zurich, EBPI, Department of Public & Global Health
name: Jahn S Fehr, Prof., MD
role: STUDY_DIRECTOR
affiliation: University of Zurich, EBPI, Department of Public & Global Health
name: Alexia Anagnostopoulos, MD
role: PRINCIPAL_INVESTIGATOR
References: