Daphnetin Capsule In the Treatment of VaScular COgnitive Impairment Without Dementia

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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 .
• Препарат Placebo
  The placebo is a Daphnetin Capsule simulants

Первичные конечные точки

• Changes in Vascular Dementia Assessment Scale-cognitive subscale (VADAS-cog) [Срок оценки: 6 months]

Вторичные конечные точки (11)

• 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 [Срок оценки: 6 months]
• Incidence of each individual event of the combined endpoint [Срок оценки: 6 months]
• Clinician Interview-Based studies Impression of Change scale-plus version(CIBIC-Plus) of change [Срок оценки: 6 months]
• Change in the Brief Mental State Evaluation Scale (MMSE) [Срок оценки: 6 months]
• Change in the Montreal Cognitive Assessment Scale (MoCA) [Срок оценки: 6 months]
• Changes in the Symbol Digit Transformation Test (SDMT) [Срок оценки: 6 months]
• Change in Clinical Dementia Rating Scale (CDR) [Срок оценки: 6 months]
• Change in Neuropsychiatric Questionnaire (NPI-Q) [Срок оценки: 6 months]
• Changes in the Activities of Daily Living Scale (ADL) [Срок оценки: 6 months]
• Changes in motor function (TUG, time to walk three meters) [Срок оценки: 6 months]
• EuroQol Five Dimensions Questionnaire (EQ-5D) [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Be 50-80 years of age (both ends included)
• Have a complaint of cognitive impairment involving memory and/or other cognitive domains that has persisted for at least 3 months
• 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
• 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
• Voluntarily participate in this study and sign an informed consent form.

Критерии исключения

• Previously diagnosed dementia; vascular cognitive impairment not associated with a condition other than dementia that may affect cognition
• Acute stroke event within 6 months
• Previously diagnosed hereditary or inflammatory small vessel disease
• Presence of congenital mental retardation and severe neurological or psychiatric disorders
• Illiteracy or severe visual or hearing impairment, severe aphasia, and other factors that may preclude cooperation with neuropsychological evaluation
• Associated depression (Hamilton Depression Scale score ≥ 17), or other unrelated serious mental illness (schizophrenia, bipolar disorder, or delirium)
• 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)
• Alcoholism, drug addiction, or ongoing use of medications that affect cognitive assessment, such as tranquilizers, sleeping pills, puberty pills, and cholinergics
• Malignant tumors that have been clearly diagnosed, vital organ failure
• Those with bleeding tendency after surgery
• Pregnant and lactating women are prohibited
• Severe hypertension (Systolic Blood Pressure(SBP)≥160mmHg and/or Diastolic Blood Pressure(DBP)≥110mmHg) is prohibited
• Previous allergy or intolerance to the ingredients of Reserpine
• The subject does not have a stable and reliable caregiver or the caregiver is unable to assist the subject in participating in the study
• Patients who have participated in other interventional clinical studies within the last 3 months or are currently participating in other interventional clinical studies.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shenyang First People's Hospital — Шэньян

Публикации

• Benisty S. [Current concepts in vascular dementia]. Geriatr Psychol Neuropsychiatr Vieil. 2013 Jun;11(2):171-80. doi: 10.1684/pnv.2013.0410. French. PMID 23803634
• Wu YT, Lee HY, Norton S, Chen C, Chen H, He C, Fleming J, Matthews FE, Brayne C. Prevalence studies of dementia in mainland china, Hong Kong and taiwan: a systematic review and meta-analysis. PLoS One. 2013 Jun 11;8(6):e66252. doi: 10.1371/journal.pone.0066252. Print 2013. PMID 23776645
• D'Onofrio G, Sancarlo D, Addante F, Ciccone F, Cascavilla L, Paris F, Picoco M, Nuzzaci C, Elia AC, Greco A, Chiarini R, Panza F, Pilotto A. Caregiver burden characterization in patients with Alzheimer's disease or vascular dementia. Int J Geriatr Psychiatry. 2015 Sep;30(9):891-9. doi: 10.1002/gps.4232. Epub 2014 Dec 4. PMID 25475248
• Kalaria RN. The pathology and pathophysiology of vascular dementia. Neuropharmacology. 2018 May 15;134(Pt B):226-239. doi: 10.1016/j.neuropharm.2017.12.030. Epub 2017 Dec 19. PMID 29273521
• Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, Burke JR, Hurd MD, Potter GG, Rodgers WL, Steffens DC, Willis RJ, Wallace RB. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1-2):125-32. doi: 10.1159/000109998. Epub 2007 Oct 29. PMID 17975326
• Javed M, Saleem A, Xaveria A, Akhtar MF. Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials. Front Pharmacol. 2022 Sep 29;13:993562. doi: 10.3389/fphar.2022.993562. eCollection 2022. PMID 36249766
• Singh L, Singh AP, Bhatti R. Mechanistic interplay of various mediators involved in mediating the neuroprotective effect of daphnetin. Pharmacol Rep. 2021 Oct;73(5):1220-1229. doi: 10.1007/s43440-021-00261-z. Epub 2021 Apr 16. PMID 33860917
• Chaudhary PK, Kim S, Kim S. Antiplatelet Effect of Daphnetin Is Regulated by cPLA2-Mediated Thromboxane A2 Generation in Mice. Int J Mol Sci. 2023 Mar 17;24(6):5779. doi: 10.3390/ijms24065779. PMID 36982853

Идентификаторы

NCT: NCT06507488 · RXSJNJLXD-2024-SYSY

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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