An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Ischemic Cerebral Vascular Disease
Overview
- Phase
- Not Applicable
- Intervention
- Calculus bovis sativus (CBS)
- Conditions
- Ischemic Cerebrovascular Disease
- Sponsor
- Tongji Hospital
- Enrollment
- 230
- Locations
- 2
- Primary Endpoint
- The National Institutes of Health Stroke Scale, NIHSS
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
The most common cause of death for Chinese patients is ischemic cerebrovascular diseases(ICVD), particularly cerebral infarction. It places a heavy burden on people, families, and society as a whole and poses considerable risks of death and disability. The disease known as CSVD has a subtle beginning, is difficult to identify, and is frequently detected only after it progresses to the point of vascular cognitive dysfunction. The primary ischemia necrosis of brain nerve cells and the activation of inflammatory cells are their pathologic processes.
According to historical Chinese medical documents, bezoar possesses properties that can help prevent seizures, treat strokes, enhance cognitive function and mental well-being, and stimulate alertness. Calculus Bovis Sativus (CBS) is the most authentic formulation of bezoar ingredients compared to other bezoar products. It has received approval from the China Food and Drug Administration for the essential treatment of comatose patients. CBS consists of three primary constituents: bilirubin, bile acids, and taurine. Scientific evidence has demonstrated that all of these components possess anti-inflammatory, antioxidant, and neuroprotective properties.
The investigators' objective is to carry out an investigator-initiated clinical study to assess the efficacy of orally administered CBS in treating ischemic cerebrovascular diseases in humans.
Investigators
Wei Wang
Professor of Neurology, President of Tongji Hospital
Tongji Hospital
Eligibility Criteria
Inclusion Criteria
- •ICVD cohort:
- •Subjects are able to understand the purpose and risks of the study, provide informed consent, and authorize the use of confidential health information in accordance with national and local privacy regulations.
- •Both men and women are welcome, and the age at the time of providing informed consent is 18-80 years (inclusive).
- •All women of childbearing age and all men must use contraceptive measures during the study and for at least 30 days after the last dose of study treatment. In addition, subjects should not donate sperm or eggs during the study and for at least 30 days after the last dose of study treatment.
- •Must be diagnosed with
- •① Ischemic stroke, according to the "Diagnosis Points of Various Cerebrovascular Diseases" of the Fourth National Cerebrovascular Disease Academic Conference, the main clinical diagnosis is ischemic stroke (cerebral infarction), 1 point ≤ NIHSS ≤ 24 points, and mRS ≤ 3 points; or ② Cerebral small vessel disease, according to the results of conventional sequence MRI examination, Fazekas score on T2 FLAIR sequence ≥ 3 points (0-6 points, the sum of paraventricular WMH score + subcortical WMH score), and mRS ≤ 3 points (mRS ≤ 4 points for those with recent subcortical small infarction within 1 month).
- •Neurological examination showed stability within 30 days before baseline (visit 1).
- •Healthy cohort:
- •Age ≥ 18 years old when signing the informed consent form
- •Healthy adult subjects without underlying diseases
Exclusion Criteria
- •Medical History and Current Health Status 1.
- •Any clinically significant cardiac, endocrine, hematologic, hepatic, immune, infectious, metabolic, urologic, pulmonary, neurological, dermatologic, psychiatric, and renal disease or other major medical history that the investigator determines would preclude participation in the clinical trial.
- •Any untreated teratoma or thymoma at the baseline visit (randomization) 1.
- •Other causes of symptoms, including CNS infection, septic encephalopathy, metabolic encephalopathy, epileptic disorders, mitochondrial disease, Klein-Levin syndrome, Creutzfeldt-Jakob disease, rheumatic disease, Reyes syndrome, or inborn errors of metabolism.
- •History of herpes simplex encephalitis within the previous 24 weeks. 1.
- •Any surgical procedure within 4 weeks prior to baseline, except laparoscopic surgery or minor surgery (defined as surgery requiring only local anesthesia or conscious sedation, i.e., surgery that does not require general, neuraxial, or regional anesthesia and can be performed on an outpatient basis; e.g., toenail surgery, mole surgery, wisdom tooth extraction), excluding thymoma or teratoma removal.
- •Planned surgery during the study (except minor surgery). 1.
- •History of severe allergic or anaphylactic reactions, or any allergic reaction that the investigator believes may be exacerbated by any component of study treatment.
- •Current or history of malignant disease, including solid tumors and hematologic malignancies (except for basal cell carcinoma and squamous cell carcinoma that have been completely resected and considered cured for at least 12 months prior to Day -1). Subjects with cancer remission for more than 5 years prior to baseline (Visit 1) may be included after discussion with the sponsor/sponsor approval.
- •A history of gastrointestinal surgery (except appendectomy or cholecystectomy performed more than 6 months before screening), irritable bowel syndrome, inflammatory bowel disease (Crohn's disease, ulcerative colitis), or other clinically significant active gastrointestinal diseases in the opinion of the investigator.
Arms & Interventions
CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in ICVD cohort
Subjects in ICVD cohort of this arm will receive general therapy plus CBS.
Intervention: Calculus bovis sativus (CBS)
CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in healthy cohort
Subjects in healthy cohort of this arm will only receive CBS.
Intervention: Calculus bovis sativus (CBS)
Outcomes
Primary Outcomes
The National Institutes of Health Stroke Scale, NIHSS
Time Frame: Up to 12 weeks after treatment initiation
To assess NIHSS of subjects within 12 weeks after treatment initiation
The Modified Rankin Scale (mRS)
Time Frame: Up to 12 weeks after treatment initiation
To assess mRS of subjects within 12 weeks after treatment initiation
Incidence and Severity of AEs and SAEs
Time Frame: Up to 14 weeks after treatment initiation
To evaluate the incidence of AEs and SAEs occurred within 14 weeks after treatment initiation
Secondary Outcomes
- The number of newly increased cerebral infarction on diffusion-weighted imaging at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The number of lacunes on T1 weighted imaging at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The number of white matter hyper-intensities on T2 flair weighted imaging at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The number of cerebral microbleeds on susceptibility weighted imaging at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The score of 36-item Short-Form (SF-36) at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The score of Mini-mental State Examination (MMSE) at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The score of Montreal cognitive assessment scale (MoCA) at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) events at week 14 compared with baseline (visit 1) and control group(Up to 14 weeks after treatment initiation)
- The score of subjective cognitive decline questionnaire (SCD) at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The score of Hamilton Anxiety Scale at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)
- The score of Hamilton Depression Scale at week 12 compared with baseline (visit 1) and control group.(Up to 12 weeks after treatment initiation)