Clinical trial NCT06507488: Daphnetin Capsule In the Treatment of VaScular COgnitive Impairment Without Dementia
Official title: Daphnetin Capsule In the Treatment of VaScular COgnitive Impairment Without Dementia - A Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cerebrovascular Disorders
Keywords: Vascular Cognitive Impairment No Dementia
Daphnetin
Effectiveness
safety
Lead sponsor: First People's Hospital of Shenyang
Sponsor class: OTHER
First posted: 2024-07-18
Enrollment: 206
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog)
timeFrame: 6 months
Secondary outcomes:
measure: 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
timeFrame: 6 months
measure: Incidence of each individual event of the combined endpoint
timeFrame: 6 months
measure: Clinician Interview-Based studies Impression of Change scale-plus version(CIBIC-Plus) of change
timeFrame: 6 months
measure: Change in the Brief Mental State Evaluation Scale (MMSE)
timeFrame: 6 months
measure: Change in the Montreal Cognitive Assessment Scale (MoCA)
timeFrame: 6 months
measure: Changes in the Symbol Digit Transformation Test (SDMT)
timeFrame: 6 months
measure: Change in Clinical Dementia Rating Scale (CDR)
timeFrame: 6 months
measure: Change in Neuropsychiatric Questionnaire (NPI-Q)
timeFrame: 6 months
measure: Changes in the Activities of Daily Living Scale (ADL)
timeFrame: 6 months
measure: Changes in motor function (TUG, time to walk three meters)
timeFrame: 6 months
measure: EuroQol Five Dimensions Questionnaire (EQ-5D)
timeFrame: 6 months
Other outcomes:
Locations:
city: Shenyang
country: China
facility: First People's Hospital of Shenyang
state: Liaoning
Study officials:
affiliation: First People's Hospital of Shenyang
name: Yi Sui, MD PhD
role: PRINCIPAL_INVESTIGATOR
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