Study on Ginkgo Biolba Extract Fifty and Mild Cognitive Impairment Associated With CSVD (GRACE)

Study on Ginkgo Biolba Extract Fifty in the Treatment of Mild Cognitive Impairment Associated With Cerebral Small Vessel Disease

This study aimed to explore the efficacy and safety of Ginkgo Biolba Extract fifty in treating mild cognitive impairment associated with cerebral small vessel disease (CSVD). Subjects included based on eligibility criteria were randomized into treatment and control groups. Patients will receive the drug or placebo for 12 months. Patients were followed at baseline and at 3 months, 6 months, and 12 months after randomization. The primary outcome was the difference from baseline in the Montreal Cognitive Assessmen (MoCA) score at 12 months after randomization.

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: Ginkgo biloba extract 50 dropping pills; Drug: Ginkgo biloba extract Ginkgo biloba extract 50 Drops simulant

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 50-75 years old, with no limitation on sex.

2. Head MRI showed SVD lesions. High white matter signal, Fazekas score ≥2 and meet one of the following requirements:

   Have ≥2 vascular risk factors (hypertension, hyperlipidemia, diabetes, current smoking); Combined lacunar foci; Combined with a new subcortical lacunar infarction (within 7 days of onset);

3. Mild vascular cognitive impairment (memory and/or other cognitive domain abnormalities lasting for at least 3 months) with a score of 18 ≤MoCA score < 26.
4. Insufficient cognitive impairment to affect independence of life (mRS≤2).
5. After enrollment, you can live in the local stable for more than two years.
6. Sign the informed consent form.

Exclusion Criteria:

1. Known or suspected allergy to the components of the investigational drug or allergic constitution.
2. With other brain diseases: Alzheimer's disease, Lewy body dementia, Parkinson's disease frontotemporal dementia, Crohn's disease, as well as other diseases that can lead to cognitive impairment, such as subdural hematoma, communicating hydrocephalus, brain tumors, drug poisoning, alcoholism, thyroid disease, and vitamin deficiency.
3. Previous diagnosis of genetic/degenerative/inflammatory related small cerebral vascular diseases, such as CADASIL, CARASIL, etc.
4. Concomitant with major depressive disorder (≥24 score in HAMD-17) or other transient organic psychosis (e.g., schizophrenia) that meets DSM-V criteria.
5. Any medication used to treat cognitive impairment in the 4 weeks prior to randomization.
6. Combined with severe neurological impairment, such as convenient hand hemiplegia, aphasia, auditory and visual impairment, the relevant examination or scale evaluation can not be completed.
7. Combined with severe gastrointestinal diseases such as indigestion, gastrointestinal obstruction, gastric and duodenal ulcers that can affect drug absorption, or inability to swallow medication.
8. Liver enzymes (ALT, AST)>2 times the upper limit of normal value, creatinine>1.2 times the upper limit of normal value, and decreased glomerular filtration rate (<90ml/min).
9. Life expectancy < 1 year, or other reasons for not being able to complete follow-up.
10. Pregnant or lactating women, or those with fertility plans.
11. Has participated in other clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ginkgo biloba extract 50 dropping pills treatment group; Ginkgo biloba extract 50 dropping pills, oral administration, 8 dropping pills /time, 3 times/day	Drug: Ginkgo biloba extract 50 dropping pills; Composition: Ginkgo ketone ester, excipient polyethylene glycol 6000. Size: 10mg ginkgolides/pill.
Placebo Comparator: Ginkgo biloba extract 50 dropping pills Simulant treatment group; Ginkgo biloba extract 50 dropping pills simulant, oral administration, 8 dropping pills /time, 3 times/day	Drug: Ginkgo biloba extract Ginkgo biloba extract 50 Drops simulant; Composition: The main ingredient is polyethylene glycol 6000 + caramel pigment, placebo and ginkgolide drops are basically the same in color, odor and appearance. Size: 10 mg analog ingredient/pill.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Montreal Cognitive Assessment Scale	Montreal Cognitive Assessment Scale (Beijing Edition) scores from 0 to 30. A higher score indicates better cognitive function.	At 12months±14days after randomization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Montreal Cognitive Assessment Scale	Montreal Cognitive Assessment Scale (Beijing Edition) scores from 0 to 30. Higher score indicates better cognitive function.	At 3months±7days and 6months±14days after randomization.
Changes from baseline in total cerebral small vessel disease burden	The severity of periventricular WMH (PV-WMH) and the deep-WMH were rated by Fazekas rating scale. The numbers of lacune and cerebral microbleed (CMB) will be collected. Perivascular spaces (PVS) in the basal ganglia was rated with the semi-quantitative rating scale developed by the Edinburg group. Total CSVD burden was the sum of points awarded for the presence or absence of four MRI markers: one point was awarded if lacunes were present, one point was awarded if CMBs were present, one point was awarded if there were moderate to severe PVS (>10) in the basal ganglia, and one point was awarded for either confluent deep WMH (Fazekas scale 2 or 3) or irregular PV-WMH extending into the deep white matter (Fazekas score 3).	At 12months±14days after randomization.
Changes from baseline in Mini-mental State Examination score	Mini-mental State Examination (MMSE) scores from 0 to 30. A higher score indicates better cognitive function.	At 3months±7days, 6months±14days and 12months±14days after randomization.
Change from baseline in the Ability Daily Living score	Ability Daily Living (ADL) scores from 14 to 56. A higher score indicates a worse ability of daily living.	At 3months±7days, 6months±14days and 12months±14days after randomization.
Change from baseline in Social functioning questionnaire	Social functioning questionnaire (FAQ) scores from 0 to 30. A higher score indicates a worse capacity of action.	At 3months±7days, 6months±14days and 12months±14days after randomization.
Change from baseline in biomarkers	Biomarkers including hs-CRP, IL-6, TNF-α, Hcy, D-dimer, Fib	At 3months±7days, 6months±14days and 12months±14days after randomization.

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 16, 2024
• First Submitted That Met QC Criteria: July 8, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 27, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: KY2024-090-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No