Evaluation of Ginkgo Biloba Extract EGb 761 on Cognitive Impairment in Post-COVID-19 Syndrome: A Randomized, Placebo-Controlled, Triple-Blind Study

The primary objective of this clinical study is to evaluate the effect of **EGb 761®** (240 mg once daily) compared to placebo on objective cognitive outcomes in participants with cognitive impairment associated with post-COVID-19 syndrome (PCS). This is clinically relevant as cognitive impairment is a significant concern for individuals recovering from PCS, and understanding the potential benefits of EGb 761® could inform treatment strategies.

Secondary objectives include:

• Evaluating the effect of EGb 761® on neuropsychiatric outcomes in participants with cognitive impairment associated with PCS.
• Assessing the effect on neurosensory outcomes in the same population.
• Investigating the impact on global and functional outcomes.
• Evaluating the safety of EGb 761® compared to placebo.

The clinical trial focuses on evaluating the effect of EGb 761® on **cognitive impairment associated with post-COVID-19 syndrome**. The study population includes both male and female outpatients aged 18 years and older. Participants are required to have a diagnosis of post-COVID-19 syndrome (PCS) as defined by the World Health Organization, with symptoms persisting for at least three months following a confirmed or probable SARS-CoV-2 infection. The trial includes individuals with persisting subjective cognitive problems for a minimum of two months, alongside objective cognitive impairment in memory or executive functioning. Additionally, participants may present with mild to moderate anxiety or depressive symptoms. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on specific inclusion criteria, ensuring that participants have a history of probable or confirmed SARS-CoV-2 infection and meet the cognitive and functional status requirements. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **placebo-controlled**, **triple-blind** study to evaluate the treatment effects and safety of **Ginkgo biloba** extract EGb 761® in participants with **cognitive impairment associated with post-COVID-19 syndrome**. The trial will involve the administration of Tebonin konzent 240 mg, a **film-coated tablet** containing a refined and quantified dry extract of **Ginkgo biloba** leaves, compared to a placebo. The study is set to commence recruitment on March 10, 2025, and is expected to conclude by March 31, 2026, with a total duration of 12 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, diagnosis of post-COVID-19 syndrome, and presence of cognitive impairment. Following successful screening, participants will be randomly assigned to receive either the active treatment or placebo. The trial includes follow-up visits at Week 6 and Week 12, during which primary endpoints will be assessed, including changes in cognitive test scores and questionnaire scores related to anxiety and depression. The end-of-study visit will occur at Week 12, marking the completion of the participant's involvement in the trial.

Participant involvement is expected to last for the entire 12-week period unless early termination is warranted. Conditions that may lead to early termination include the occurrence of adverse events, adverse drug reactions, or serious adverse events that compromise participant safety. The primary endpoints of the study focus on changes from baseline in cognitive test scores, such as the Digit Span and Verbal Fluency tests, as well as changes in questionnaire scores for anxiety and depression. The trial aims to provide valuable insights into the efficacy and safety of **Ginkgo biloba** extract in addressing cognitive impairment associated with post-COVID-19 syndrome.

The clinical trial involves the administration of **Tebonin konzent 240 mg**, a **film-coated tablet** containing a refined and quantified dry extract of **Ginkgo biloba** leaves. The extract is standardized to contain 22.0 to 27.0% flavonoids expressed as flavone glycosides, 2.8 to 3.4% ginkgolides A, B, and C, and 2.6 to 3.2% bilobalide. The extraction solvent used is acetone 60% (m/m). The medication is administered orally at a dosage of 240 mg once daily (QD). The maximum treatment period is 12 weeks, with a total maximum dose of 20,160 mg. The product is manufactured by Dr. Willmar Schwabe GmbH & Co. KG and is not a pediatric formulation.

The study also includes a **placebo** group, which receives a film-coated, round, yellow tablet for oral use that contains no active substance. The placebo is designed to match the experimental medication in appearance to maintain the triple-blind nature of the study. The placebo is administered with the same frequency and route as the experimental medication, ensuring consistency in the administration process.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen. The trial is designed to evaluate the effects of the Ginkgo biloba extract on cognitive impairment associated with post-COVID-19 syndrome, comparing the outcomes with those of the placebo group.

Efficacy in this clinical trial will be assessed by evaluating the effect of EGb 761® (240 mg once daily) compared to placebo on objective cognitive outcomes in participants with cognitive impairment associated with post-COVID-19 syndrome. The primary endpoints for efficacy evaluation include changes from baseline to Week 6 and Week 12 in various cognitive and symptom assessment scores. These assessments will utilize the Digit Span Forward and Backward Test, Verbal Fluency Test, Trail-Making Test (TMT A + B), California Verbal Learning Test (CVLT), and d2-R test. Additionally, changes in questionnaire scores such as the Generalized Anxiety Disorder-7 (GAD-7) test, Patient Health Questionnaire-9 (PHQ-9) test, and the 11-point box scale for vertigo and tinnitus will be measured.

Further assessments will include changes in scores from the Clinical Global Impression-Severity (CGI-S), Post COVID Functional Status Scale (PCFSS), Modified Fatigue Impact Scale (MFIS), Modified Patient Experience Measure-Daily Symptom Questionnaire (mPEM-DSQ), and the Shortness of Breath Questionnaire-Long COVID (SBQ-LC) test. The Clinical Global Impression-Improvement (CGI-I) will be evaluated at Week 6 and Week 12. The number of patients experiencing adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) will also be recorded as part of the efficacy assessment. These parameters will be collected and analyzed at specified timepoints to determine the treatment's impact on cognitive impairment associated with post-COVID-19 syndrome.