Cerebrovascular Disorders
Conditions
Keywords
Vascular Cognitive Impairment No Dementia, Daphnetin, Effectiveness, safety
Brief summary
The purpose of this clinical trial is to understand and evaluate the clinical efficacy and safety of Daphnetin Capsule in patients with vascular cognitive impairment. Changes in the Vascular Dementia Assessment Scale-cog(VADAS-cog) at 6 months were evaluated. Although Daphnetin has a dual neurovascular protective effect, however, there is still a lack of relevant high-quality studies on its role in patients with vascular cognitive impairment, especially in patients with vascular cognitive impairment in non-dementia (VCI-ND), whether it has a role in improving cognitive status needs to be urgently explored in high-quality clinical studies. Researchers are comparing Daphnetin to placebo (a drug-free analog) to see if Daphnetin is effective in treating vascular cognitive impairment. Participants will take either Daphnetin or placebo daily for six months, with follow-up visits every three months and completion of a case report form.
Detailed description
Vascular cognitive impairment (VCI) is caused by ischemic or hemorrhagic strokes and other cerebrovascular diseases, leading to cognitive and memory function impairment. With the aging population and high incidence of cerebrovascular diseases in China, Vascular cognitive impairment (VCI) prevalence is rising, increasing the disease burden. However, due to the complexity of Vascular cognitive impairment (VCI) symptoms and imaging changes, targeted therapies are currently lacking. Daphnetin, a coumarin derivative, has shown promise in treating various diseases and has gained significant attention recently. It offers "triple protection" for blood, blood vessels, and ischemic tissues by inhibiting inflammation, anticoagulation, and thrombosis, protecting endothelial structures, and regulating vasoactive substances. Daphnetin is particularly beneficial for cardio-cerebral vascular disease, diabetes mellitus, and microvascular complications. It also expands peripheral blood vessels, improving circulation and alleviating vascular occlusive diseases. Research indicates that Daphnetin's anti-inflammatory effects can inhibit neuroinflammation, promote synaptic growth, and enhance neuronal survival, protecting nerve cells and repairing damage. Despite these benefits, there is a lack of high-quality studies on Daphnetin's role in non-dementia vascular cognitive impairment (VCI-ND). This project aims to evaluate the clinical efficacy and safety of oral Daphnetin capsules in treating Vascular cognitive impairment (VCI) through a prospective, randomized, double-blind, placebo-controlled study. Patients with vascular cognitive dysfunction confirmed by cerebral small vessel disease imaging will participate. The study will follow the international FINESSE framework, comparing Daphnetin to a placebo over six months, with follow-up visits and case report forms completed every three months.
Interventions
DRUGDaphnetin Capsule
Daphnetin, chemically known as 7,8-dihydroxycoumarin, also known as ZuShiMaJiaSu, is a class of coumarin derivatives derived from different Daphnetin genus plant .
DRUGPlacebo
The placebo is a Daphnetin Capsule simulants
Sponsors
First People's Hospital of Shenyang
Fourth People's Hospital of Shenyang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Be 50-80 years of age (both ends included) 2. Have a complaint of cognitive impairment involving memory and/or other cognitive domains that has persisted for at least 3 months 3. Have a cognitive level that is neither normal nor demented according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Criteria ( DSM-V criteria）, a Montreal Cognitive Assessment (MoCA scale) score \<26 and ≥18, and a Clinical Dementia Rating (CDR) scale score of ≥0.5 in at least one domain and an overall CDR score ≤1 4. Have a cognitive level that is neither normal nor demented according to DSM-V criteria, a MoCA scale score \<26 and ≥18, and a CDR scale score of ≥0.5 in at least one domain and an overall CDR score ≤1 5. Voluntarily participate in this study and sign an informed consent form.
Exclusion criteria
1. Previously diagnosed dementia; vascular cognitive impairment not associated with a condition other than dementia that may affect cognition 2. Acute stroke event within 6 months 3. Previously diagnosed hereditary or inflammatory small vessel disease 4. Presence of congenital mental retardation and severe neurological or psychiatric disorders 5. Illiteracy or severe visual or hearing impairment, severe aphasia, and other factors that may preclude cooperation with neuropsychological evaluation 6. Associated depression (Hamilton Depression Scale score ≥ 17), or other unrelated serious mental illness (schizophrenia, bipolar disorder, or delirium) 7. Combined severe cardiac, pulmonary, and renal insufficiency (creatinine \> 2.0 mg/dl or 177 μ mol/L), and severe hepatic impairment (aminotransferases more than 3 times normal) 8. Alcoholism, drug addiction, or ongoing use of medications that affect cognitive assessment, such as tranquilizers, sleeping pills, puberty pills, and cholinergics 9. Malignant tumors that have been clearly diagnosed, vital organ failure 10. Those with bleeding tendency after surgery 11. Pregnant and lactating women are prohibited 12. Severe hypertension (Systolic Blood Pressure(SBP)≥160mmHg and/or Diastolic Blood Pressure(DBP)≥110mmHg) is prohibited 13. Previous allergy or intolerance to the ingredients of Reserpine 14. The subject does not have a stable and reliable caregiver or the caregiver is unable to assist the subject in participating in the study 15. Patients who have participated in other interventional clinical studies within the last 3 months or are currently participating in other interventional clinical studies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) | 6 months | Vascular Dementia Assessment Scale-cognitive subscale（VADAS-cog） is a revision of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) to be a better measure in vascular conditions，The lowest score is 0, with higher scores representing higher levels of cognitive dysfunction and poorer status of the patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of combined endpoints: including new stroke (ischemic Trial of ORG 10172 in Acute Stroke Treatment typing [TOAST typing] or hemorrhagic)/transient ischemic attack, myocardial infarction, new-onset dementia, death | 6 months | For categorical indicators, the stratified Cochran- Mantel-Haenszel (CMH) test will be used for analysis. |
| Incidence of each individual event of the combined endpoint | 6 months | For categorical indicators, the stratified Cochran- Mantel-Haenszel (CMH) test will be used for analysis. |
| Clinician Interview-Based studies Impression of Change scale-plus version(CIBIC-Plus) of change | 6 months | Consists of three parts The clinician's impression of change is an assessment of change from baseline, not an assessment of severity. The clinician may refer to his/her own baseline information compiled in Part I when making the assessment of change. The clinician's assessment of impression of change should then be replicated in the main study case report form.The score of CIBIC-plus ranges from 1 to 7, and the score of 1-3 indicates improvement, 4 means no changed, and 5-7 indicates worse. |
| Change in the Brief Mental State Evaluation Scale (MMSE) | 6 months | Each correct item is scored as 1 point, and errors are scored as 0 points. The total score ranges from 0 to 30, and the cut-off value for normal and abnormal is related to the level of education; ≤17 points for the illiterate (no education) group, ≤20 points for the elementary school (≤6 years of education) group, and ≤24 points for the secondary school or above (\>6 years of education) group. Cognitive deficits are considered to be below the cut-off value and normal above it. |
| Change in the Montreal Cognitive Assessment Scale (MoCA) | 6 months | The MoCA scale is a 30-point scale, with ≥26 normal, 18-26 mild cognitive impairment (MCI), 10-17 moderate, and less than 10 severe.Patients with MCI scored approximately 22 (19-25) points, and patients with AD scored between 11-21 points. |
| Changes in the Symbol Digit Transformation Test (SDMT) | 6 months | Completion of the SDMT scale within 90 seconds, with a total score of 0-110; the lower the score, the more severe the degree of cognitive impairment |
| Change in Clinical Dementia Rating Scale (CDR) | 6 months | The total score ranges from 0 to 18,The higher the score, the more demented the patient is, the worse the state is. |
| Change in Neuropsychiatric Questionnaire (NPI-Q) | 6 months | Presence of symptoms (1-2): 1=present 2=absent. Frequency (1-4 points): 1=occasional, less than weekly; 2=frequent, about weekly; 3=several times a week but less than daily; 4=very frequent, once or more at a time or continuously. Severity (on a scale of 1 to 3): 1=mild, perceptible but not obvious; 2=moderate, obvious but not very prominent; 3=severe, very prominent changes. The degree of distress caused by the symptom to the caregiver (0-5 points): 0 = no distress; 1 = very mild distress, caregiver does not need to take steps to cope; 2 = mild distress, caregiver copes easily; 3 = moderate distress, caregiver struggles to cope; 4 = severe, caregiver is barely able to cope; 5 = extreme distress, caregiver is unable to cope. The higher the score the more severe |
| Changes in the Activities of Daily Living Scale (ADL) | 6 months | 1 = can do it all by myself; 2 = can still do it with some difficulty; 3 = need help 4 = cannot do it at all. When the patient never does it but is able to do it, it is rated as 1, never does it but has difficulty doing it but does not need help, 2, never does it but needs help, 3, never does it and is unable to do it, 4. The range of scores is from 20 to 80, and a score of \>23 is considered to be cognitively impaired. |
| Changes in motor function (TUG, time to walk three meters) | 6 months | Change in motor score (TUG, time to walk three meters) at 6 months relative to baseline |
| EuroQol Five Dimensions Questionnaire (EQ-5D) | 6 months | The EuroQol Five Dimensions Questionnaire (EQ-5D) health description system consists of five dimensions: mobility (MO), self-care (SC), ability to perform activities of daily living (UA), pain or discomfort (PD), and anxiety or depression (AD), each of which can be reported separately as "no problem, moderate problem, or severe problem".Self-rated health on a scale of 0 to 100, the higher the score the better your health is considered to be. |
Countries
China
Contacts
CONTACTYi Sui, MD PhD
CONTACTMingming Dong, MD
PRINCIPAL_INVESTIGATORYi Sui, MD PhD
The Fourth People's Hospital of Shenyang, China Medical University
Outcome results
None listed