Daphnetin Capsule In the Treatment of VaScular COgnitive Impairment Without Dementia (DISCO)

August 21, 2025 updated by: Dr. Yi Sui, First People's Hospital of Shenyang

Daphnetin Capsule In the Treatment of VaScular COgnitive Impairment Without Dementia - A Randomized, Double-blind, Placebo-controlled Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

206

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Liaoning
      • Shenyang, Liaoning, China, 110041
        • Recruiting
        • Shenyang First People's Hospital
        • Principal Investigator:
          • Wei Bian, MD
        • Sub-Investigator:
          • Hong Wang
        • Sub-Investigator:
          • Yang Zhao
        • Contact:
        • Contact:
        • Principal Investigator:
          • Li Li, MD PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Daphnetin
oral Daphnetin Capsule three capsules/tid for up to six months.
Drug: Daphnetin Capsule
Daphnetin, chemically known as 7,8-dihydroxycoumarin, also known as ZuShiMaJiaSu, is a class of coumarin derivatives derived from different Daphnetin genus plant .
Other Names:
  • 7,8-dihydroxycoumarin
Placebo Comparator: Placebo
oral Placebo (Daphnetin Capsule simulants) three capsules/tid for up to six months.
Drug: Placebo
The placebo is a Daphnetin Capsule simulants

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog)
Time Frame: 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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of each individual event of the combined endpoint
Time Frame: 6 months
For categorical indicators, the stratified Cochran- Mantel-Haenszel (CMH) test will be used for analysis.
6 months
Change in the Brief Mental State Evaluation Scale (MMSE)
Time Frame: 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.
6 months
Change in the Montreal Cognitive Assessment Scale (MoCA)
Time Frame: 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.
6 months
Changes in the Symbol Digit Transformation Test (SDMT)
Time Frame: 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
6 months
Change in Neuropsychiatric Questionnaire (NPI-Q)
Time Frame: 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
6 months
Changes in the Activities of Daily Living Scale (ADL)
Time Frame: 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.
6 months
Changes in motor function (TUG, time to walk three meters)
Time Frame: 6 months
Change in motor score (TUG, time to walk three meters) at 6 months relative to baseline
6 months
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
Time Frame: 6 months
For categorical indicators, the stratified Cochran- Mantel-Haenszel (CMH) test will be used for analysis.
6 months
Clinician Interview-Based studies Impression of Change scale-plus version(CIBIC-Plus) of change
Time Frame: 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.
6 months
Change in Clinical Dementia Rating Scale (CDR)
Time Frame: 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.
6 months
EuroQol Five Dimensions Questionnaire (EQ-5D)
Time Frame: 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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First People's Hospital of Shenyang

Collaborators

The Fourth People's Hospital of Shenyang

Investigators

  • Principal Investigator: Yi Sui, MD PhD, The Fourth People's Hospital of Shenyang, China Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 7, 2025

Primary Completion (Actual)

July 7, 2025

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

July 12, 2024

First Submitted That Met QC Criteria

July 12, 2024

First Posted (Actual)

July 18, 2024

Study Record Updates

Last Update Posted (Estimated)

August 28, 2025

Last Update Submitted That Met QC Criteria

August 21, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RXSJNJLXD-2024-SYSY

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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