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Completed

NCT Number: NCT05890534

Pycnogenol® in Post-COVID-19 Condition

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

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Key information

Conditions

Post COVID-19 Condition COVID-19 Chronic Disease Coronaviridae Infections Coronavirus Infections Disease Attributes Infections Long COVID Lung Diseases Nidovirales Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Viral Post-Acute COVID-19 Syndrome Post-Infectious Disorders RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Zurich, Epidemiology, Biostatistics and Prevention Institute, Department of Public & Global Health

Zurich, 8001, Switzerland

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Pycnogenol®

Drug

Single center, quadruple blind randomized controlled trial comparing Pycnogenol® versus Placebo.

Placebo

Drug

Single center, quadruple blind randomized controlled trial comparing Pycnogenol® versus Placebo.

Primary outcomes

  1. Health status (EQ-VAS)

    Time frame: Change from baseline to 12 weeks

    EQ-Visual Analogue Scale (EQ-VAS also known as "Feeling thermometer") assessed daily over 7 consecutive days prior to the baseline and at the end of the follow-up 2 visit (i.e., study end after 12 weeks). The scale ranges from 0-100 with 0 representing worst health status and 100 representing best health status.

Secondary outcomes

  1. Post COVID-19 symptoms

    Time frame: Change from baseline to 12 weeks

    Symptoms (present/not present) and symptom severity (5- point Likert scale: 1=not bad at all, 2=mild, 3=moderate, 4=severe, 5=very severe) will be assessed using a self-administered online questionnaire. Symptoms will also be recorded in a paper diary and completed on a weekly basis.

  2. Fatigue

    Time frame: Change from baseline to 12 weeks

    Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F). 13-item questionnaire with a 7-day recall period assessed at baseline and after 12 weeks. The level of fatigue is measured on a 5-point Likert scale (4 = not at all fatigued to 0 = very much fatigued). Individual item scores are summed, with lower scores indicating more severe fatigue.

  3. Dyspnea

    Time frame: Change from baseline to 12 weeks

    Symptom domain of the Chronic Respiratory Questionnaire (CRQ) assessed at baseline and after 12 weeks. The questionnaire contains 5 questions; 7-point Likert-type scale ranging from 1 (most severe dyspnea) to 7 (no dyspnea).

  4. Cognitive function

    Time frame: Change from baseline to 12 weeks

    Montreal Cognitive Assessment (MoCA) assessed at baseline and after 12 weeks. The cut-off score < 26 for cognitive impairment will be used in this study.

  5. Anxiety and depression

    Time frame: Change from baseline to 12 weeks

    Hospital, Anxiety and Depression Scale (HADS) assessed at baseline and after 12 weeks. Symptoms of depression and anxiety (14 questions, 4-point Likert-type scale).

  6. Health-related quality of life (EQ-5D-5L)

    Time frame: Change from baseline to 12 weeks

    The EQ-5D-5L assesses the 5 dimensions mobility, self-care, usual activities, pain/discomfort, anxiety/depression. The EQ-5D-5L scores each dimension on five levels of severity ranging from 1 = "no problems" to 5 = "extreme problems. The instrument will be used at baseline and after 12 weeks.

  7. Functional exercise capacity

    Time frame: Change from baseline to 12 weeks

    A 30 second Sit-to-Stand (STS) will be performed at baseline and after 12 weeks. The number of repetitions that the participant completes the full sit-to-stand movement on a chair during 30 seconds. A familiarisation test will be done at the screening visit to rule out potential learning effects.

  8. Physical activity

    Time frame: Change from baseline to 12 weeks

    Physical activity measured with an accelerometer (ActiGraph wGT3X-BT, Pensacola, FL, USA), which is worn at the right hip over 8 consecutive days prior to the baseline and 12 week study visit. Number of daily steps and time spent in different intensity domains (min per day) will be analysed.

  9. Soluble Thrombomodulin (sTM)

    Time frame: Change from baseline to 12 weeks

    Blood biomarker of endothelial health measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  10. von Willebrand Factor antigen (VWF:Ag)

    Time frame: Change from baseline to 12 weeks

    Blood biomarker of endothelial health measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  11. Syndecan-1

    Time frame: Change from baseline to 12 weeks

    Blood biomarker of endothelial health measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  12. Circulating Cascular Cell Adhesion Molecule-1 (sVCAM 1)

    Time frame: Change from baseline to 12 weeks

    Blood biomarker of endothelial health measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  13. C-reative protein (CRP)

    Time frame: Change from baseline to 12 weeks

    Marker of inflammation (serum) measured at baseline and after 12 weeks by a certified laboratory (Analytica, Zurich, Switzerland).

  14. Interleukine 6 (IL 6)

    Time frame: Change from baseline to 12 weeks

    Marker of inflammation measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  15. sCD40L

    Time frame: Change from baseline to 12 weeks

    Marker of coagulation and platelet function measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  16. sP selectin

    Time frame: Change from baseline to 12 weeks

    Adhesion molecule measured with Enzyme-linked Immunosorbent Assay (ELISA) or Luminex (bead-based immunoassay) at baseline and after 12 weeks.

  17. D-Dimer

    Time frame: Change from baseline to 12 weeks

    Marker of coagulation and platelet function measured in citrate blood at baseline and after 12 weeks by certified laboratory (Analytica, Zurich, Switzerland).

  18. Activated partial thromboplastin time (aPTT)

    Time frame: Change from baseline to 12 weeks

    Marker of coagulation and platelet function measured in citrate blood at baseline and after 12 weeks by certified laboratory (Analytica, Zurich, Switzerland).

  19. International normalized ratio (INR) blood test

    Time frame: Change from baseline to 12 weeks

    Marker of coagulation and platelet function measured in citrate blood at baseline and after 12 weeks by certified laboratory (Analytica, Zurich, Switzerland).

  20. Total antioxidant capacity (TAC)

    Time frame: Change from baseline to 12 weeks

    Marker of oxidative stress measured in blood plasma at baseline and after 12 weeks. TAC will be measured using the well-established Ferric Reduction Capability of Plasma (FRAP) method using a commercially available kit.

  21. Aspartate aminotransferase (ASAT)

    Time frame: Change from baseline to 12 weeks

    Marker of liver function measured in blood serum at baseline and after 12 weeks by a certified laboratory (Analytica, Zurich, Switzerland).

  22. Alanine aminotransferase (ALAT)

    Time frame: Change from baseline to 12 weeks

    Livery enzyme measured in blood serum at baseline and after 12 weeks by a certified laboratory (Analytica, Zurich, Switzerland).

  23. Gamma glutamyltransferase (γ-GT)

    Time frame: Change from baseline to 12 weeks

    Livery enzyme measured in blood serum at baseline and after 12 weeks by a certified laboratory (Analytica, Zurich, Switzerland).

  24. Creatinine

    Time frame: Change from baseline to 12 weeks

    Creatinine including clearance measured in blood serum at baseline and after 12 weeks by a certified laboratory (Analytica, Zurich, Switzerland).

Other outcomes

  1. Adherence to study products

    Time frame: Baseline to 12 weeks

    Adherence to study products (Pycnogenol® and Placebo) will be evaluated during the two follow-up visits (6 and 12 weeks after baseline visit) and the two follow-up phone calls using a standardized assessment form. The number of capsules returned at the study visits will be counted and entered into the database.

  2. Post-exertional malaise

    Time frame: Baseline to 12 weeks

    Post-exertional malaise is a frequent symptom in post COVID-19 condition. Study visits and measurements may pose a burden for the participants. At each visit, starting with the baseline visit, participants will be asked whether they experienced a worsening of their symptoms within 3 days after the last study visit (i.e., after 12 weeks). A self-administered questionnaire will be used.

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Registry information

Official study title

Pycnogenol® in People With Post-COVID-19 Condition: a Quadruple-blind, Randomized, Placebo-controlled Trial

Acronym: PYCNOVID

Important dates

Study start
2023
Primary completion
2024
Study completion
2025
First posted
Jun 6, 2023
Registry last updated
Apr 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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