A Study Testing How Well the Drug Extract of Ginkgo Biloba Leaves Tablets Works for People With Memory or Thinking Problems After a Stroke When Added to Standard Treatment

Official title

Pragmatic Open-label, Parallel-group Clinical Trial on the Effectiveness of Extract of Ginkgo Biloba Leaves Tablets as add-on to Standard of Care in Participants With Cognitive Impairment After an Acute Ischemic Stroke (GiCIIS)

Overview

The goal of this clinical trial is to learn if Extract of Ginkgo Biloba Leaves Tablets help improve thinking and memory in people aged 55 years and older who had an ischemic stroke (a type of stroke caused by a blocked blood vessel in the brain). It will also look at how safe the Extract of Ginkgo Biloba Leaves Tablets are. The main questions it aims to answer are: * Do the Extract of Ginkgo Biloba Leaves Tablets help people with memory or thinking problems after an ischemic stroke? * What medical problems do people have when taking the Extract of Ginkgo Biloba Leaves Tablets ? Researchers will compare people who take the Extract of Ginkgo Biloba Leaves Tablets along with their usual post-stroke treatment to people who only receive their usual post-stroke treatment. Participants will: * Have had an ischemic stroke confirmed by MRI (Magnet Resonance Imaging, a magnetic scan that helps seeing inside the body in great detail) 7 to 14 days before joining the study * Take Extract of Ginkgo Biloba Leaves Tablets (240 mg per day) in addition to usual post-stroke treatment for 12 months, or receive only usual post-stroke treatment for 12 months * Be treated initially at hospitals across China * Visit the clinic 4, 26, and 52 weeks following the baseline for checkups and tests, and receive follow-up calls after 12 and 38 weeks.

Detailed description

This is a prospective, multicenter, pragmatic, open-label, parallel-group, randomized clinical trial to investigate the effectiveness and safety of Extract of Ginkgo Biloba Leaves Tablets as add-on to standard of care in participants with cognitive impairment after an acute ischemic stroke (AIS). The trial will be conducted at hospitals across China. Participants that had had a non-disabling overt AIS (i. e., NIHSS (National Institutes of Health Stroke Scale) ≤ 5, mRS (Modified Rankin Scale) ≤ 2 at the day of screening), confirmed by MRI (magnetic resonance imaging), 7 to 14 days before screening will be randomized 1:1 to Extract of Ginkgo Biloba Leaves Tablets (240 mg total dose per day, (3 x (2 x 40 mg)) in addition to standard of care or standard of care alone. The total duration of the trial will be 52 weeks per trial participant.

Interventions

• Drug Extract of Ginkgo Biloba Leaves Tablets 240 mg (2 x 40 mg, t.i.d.)
  3 x 2 film-coated tablets with 40 mg Extract of Ginkgo Biloba Leaves Tablets daily for 52 weeks plus standard of care in accordance with treatment guidelines
• Other Standard of care (SoC) Group
  Individualized therapy in accordance with treatment guideline from the Chinese Stroke Association

Primary outcome measures

• Change in Montreal Cognitive Assessment (MoCA) Total Score [Time frame: From baseline to Week 26 (Visit 4) and Week 52 (Visit 6)]
• Change in Cognitive Function Using Trail Making Test (TMT) Parts A and B [Time frame: Change from baseline to Week 26 (Visit 4) and Week 52 (Visit 6)]
• Change in Cognitive Processing Speed Using Symbol Digit Modalities Test (SDMT) [Time frame: Change from baseline to Week 26 (Visit 4) and Week 52 (Visit 6)]
• Change in Verbal Fluency Performance Using Verbal Fluency Test (VFT) [Time frame: Change from baseline to Week 26 (Visit 4) and Week 52 (Visit 6)]
• Change in Clinical Global Impression of Change Using ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change) [Time frame: Change from baseline to Week 26 (Visit 4) and Week 52 (Visit 6)]
• Change in Neurological Impairment Using National Institutes of Health Stroke Scale (NIHSS) [Time frame: Change from Baseline to Week 4 (Visit 1), Week 26 (Visit 4) and Week 52 (Visit 6)]
• Change in Neurological Impairment Using Modified Rankin Scale (mRS) [Time frame: Change from Baseline to Week 4 (Visit 1), Week 26 (Visit 4) and Week 52 (Visit 6)]
• Any new stroke event (ischemic stroke or hemorrhagic stroke) at Week 4, Week 12, Week 26, Week 38 and Week 52. [Time frame: Week 4, Week 12, Week 26, Week 38 and Week 52]

Eligibility criteria

Inclusion criteria

• Male and female participants aged ≥ 55 years who gave their informed consent.
• Non-disabling overt acute ischemic stroke (NIHSS (National Institutes of Health Stroke Scale) ≤ 5, mRS (Modified Rankin Scale) ≤ 2 at the day of screening) confirmed by magnetic resonance imaging, and at least 7 but no longer than 14 days before baseline.
• Cognitive impairment (MoCA (Montreal Cognitive Assessment)) total score (corrected) < 23 for participants with up to 12 years of education, or MoCA total score < 22 if more than 12 years of education).
• Sufficient Chinese language skills to understand and respond to all interview questions, complete questionnaires and undergo neuropsychological testing.

Exclusion criteria

• Participation in another experimental drug trial at the same time or within the past 4 weeks before enrollment.
• Aphasia, dysarthria, apraxia or paresis of the dominant upper extremity, severe and insufficiently corrected loss of vision or hearing, severe language difficulties or any other disability that may prevent the participant from cooperating adequately in the trial or that may interfere with neuropsychological test performance.
• Pre-stroke cognitive impairment (16-item Informant Questionnaire on Cognitive Decline (IQCODE) score ≥ 3.3), preexisting major neurocognitive disorder (e. g., dementia due to Alzheimer's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia).
• Cardiogenic ischemic stroke, atrial fibrillation, or any other conditions that require the intake of anticoagulants.
• Conditions that require the administration of thrombolytics at day of Screening or Visit 1.
• Index acute ischemic stroke with hemorrhagic transformation.
• Intake of traditional Chinese medicines.
• Major neurological disorder, including intracranial hemorrhage, delirium, Parkinson's disease, brain tumor, alcohol-associated brain damage, infectious CNS disease, epilepsy, recent brain trauma, subdural hematoma, HIV-associated cognitive disorder, Huntington's disease, Pick's disease, Wilson's disease, normal pressure hydrocephalus, hydrocephalus, progressive supra-nuclear palsy, Creutzfeldt-Jakob disease, etc.
• Major depression or generalized anxiety disorder.
• Active malignant disease.
• Alcohol addiction or substance abuse.
• Known hypersensitivity to Ginkgo biloba, Ginkgo biloba extract or any ingredient of the drug under trial.
• Any circumstances that prevent the participant to be followed up at the scheduled intervals. Hospitalization of the participant for long-term treatment or nursing home placement for bedside care (assisted living facility residence or stay in a rehabilitation facility is acceptable if the participant is not bedridden and does not need general bedside nursing, and if an informant is available who sees the participant on a regular basis and accompanies him/her to the trial visits).
• Severe comorbidity with life expectancy < 12 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 40 centers

• The People's Hospital of Anyang City — Anyang
• Baotou Central Hospital — Baotou
• Tiantan Hospital — Beijing
• Beipiao Central Hospital — Beipiao
• Benxi Central Hospital — Benxi
• The First People's Hospital of Chenzhou — Chenzhou
• Affiliated Hospital of Chifeng University — Chifeng
• Affiliated Zhongshan Hospital of Dalian University — Dalian
• … and 32 more centers

Publications

• Wu Y, Wang M, Ren M, Xu W. The effects of educational background on Montreal Cognitive Assessment screening for vascular cognitive impairment, no dementia, caused by ischemic stroke. J Clin Neurosci. 2013 Oct;20(10):1406-10. doi: 10.1016/j.jocn.2012.11.019. Epub 2013 Jul 24. PMID 23891119
• Liu L, Li Z, Zhou H, Duan W, Huo X, Xu W, Li S, Nie X, Liu H, Liu J, Sun D, Wei Y, Zhang G, Yuan W, Zheng L, Liu J, Wang D, Miao Z, Wang Y. Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update. Stroke Vasc Neurol. 2023 Dec 29;8(6):e3. doi: 10.1136/svn-2023-002998. PMID 38158224
• Herrschaft H, Nacu A, Likhachev S, Sholomov I, Hoerr R, Schlaefke S. Ginkgo biloba extract EGb 761(R) in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psychiatr Res. 2012 Jun;46(6):716-23. doi: 10.1016/j.jpsychires.2012.03.003. Epub 2012 Mar 27. PMID 22459264
• El Husseini N, Katzan IL, Rost NS, Blake ML, Byun E, Pendlebury ST, Aparicio HJ, Marquine MJ, Gottesman RF, Smith EE; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; and Council on Lifestyle and Cardiometabolic Health. Cognitive Impairment After Ischemic and Hemorrhagic Stroke: A PMID 37125534
• Cui M, You T, Zhao Y, Liu R, Guan Y, Liu J, Liu X, Wang X, Dong Q. Ginkgo biloba extract EGb 761(R) improves cognition and overall condition after ischemic stroke: Results from a pilot randomized trial. Front Pharmacol. 2023 Mar 29;14:1147860. doi: 10.3389/fphar.2023.1147860. eCollection 2023. PMID 37063270

Identifiers

NCT: NCT07220538 · D.01.02.2.04 · ChiCTR2500107051

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• ChiCTR ChiCTR2500107051 (Chinese Clinical Trial Registry)

View this study on ClinicalTrials.gov ↗