Efficacy and Safety of Calculus Bovis Sativus (CBS) for Ischemic Cerebral Vascular Disease (CBSinICVD)

NCT06474507 | Recruiting

• 1 other identifier: CBSinICVD
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 2

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.

Conditions

Ischemic Cerebrovascular Disease; Acute Ischemic Stroke; Cerebral Small Vessel Diseases

Keywords

Calculus Bovis Sativus; Neuroprotection; Neuroinflammation

Outcome Measures

Primary Outcomes (3)

• The Modified Rankin Scale (mRS)

  To assess mRS of subjects within 12 weeks after treatment initiation

  Up to 12 weeks after treatment initiation

• The National Institutes of Health Stroke Scale, NIHSS

  To assess NIHSS of subjects within 12 weeks after treatment initiation

  Up to 12 weeks after treatment initiation

• Incidence and Severity of AEs and SAEs

  To evaluate the incidence of AEs and SAEs occurred within 14 weeks after treatment initiation

  Up to 14 weeks after treatment initiation

Secondary Outcomes (11)

• 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 Mini-mental State Examination (MMSE) at week 12 compared with baseline (visit 1) and control group.

  Up to 12 weeks after treatment initiation

Other Outcomes (4)

• Fecal flora abundance at week 12 compared with baseline (visit 1).

  Up to 12 weeks after treatment initiation

• Fecal metabolomics analysis at week 12 compared with baseline (visit 1).

  Up to 12 weeks after treatment initiation

• Profiling of cell subtypes at week 12 compared with baseline (visit 1).

  Up to 12 weeks after treatment initiation

Study Arms (3)

CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in ICVD cohort

EXPERIMENTAL

Subjects in ICVD cohort of this arm will receive general therapy plus CBS.

Drug: Calculus bovis sativus (CBS)

Control therapy: no intervention, in ICVD cohort.

NO INTERVENTION

Subjects in ICVD cohort of this arm will only receive general therapy.

CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in healthy cohort

EXPERIMENTAL

Subjects in healthy cohort of this arm will only receive CBS.

Drug: Calculus bovis sativus (CBS)

Interventions

Calculus bovis sativus (CBS) DRUG

Subjects will orally receive 100mg CBS per day from day 1 to day 84.

CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in ICVD cohort; CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in healthy cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Medical History and Current Health Status 1.1. 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) 1.3. 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. 1.5. 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). 1.7. 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.
• A history of clinically significant recurrent or active gastrointestinal symptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days before screening, including the need to start symptomatic treatment (e.g., start medication for gastroesophageal reflux disease) or a change in symptomatic treatment within 90 days before screening (e.g., dose increase).
• A history of diverticulitis or concurrent severe gastrointestinal (GI) abnormalities (e.g., symptomatic diverticular disease) because the investigator believes that this may lead to an increased risk of complications such as GI perforation.
• A history of blood donation (1 unit or more), plasma donation, or platelet donation within 90 days before screening.
• Active suicidal ideation within 6 months before screening, or a history of suicide attempt within 3 years before screening.
• Based on the investigator's judgment, there are serious diseases or abnormalities in the clinical laboratory test results that prevent the patient from completing the study or participating in the study safely.
• Pregnant or lactating, or planning to become pregnant during the study or within 3 months after the last dose of the study drug; women of childbearing potential must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result before the start of the study.
• The subject's mental or physical condition will hinder the evaluation of efficacy and safety.
• Systolic blood pressure \>150 mmHg or \<90 mmHg after sitting still for 5 minutes or before dosing at screening. If out of range, it can be measured again at screening and before dosing. If the repeated measurement value is still out of range, the subject shall not receive the drug.
• Subjects with second or third degree atrioventricular block or sick sinus syndrome, poorly controlled atrial fibrillation, severe or unstable angina, congestive heart failure, myocardial infarction, or significant ECG abnormalities, including QTc\>450 msec (male) or 470 msec (female), where QTc is determined based on the Fridericia correction method, within 3 months prior to the screening visit.

Sponsors & Collaborators

• Tongji Hospital: lead
• Jianmin Pharmaceutical Group Co., LTD.: collaborator

Study Sites (2)

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430000, China

RECRUITING

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MeSH Terms

Conditions

Ischemic Stroke; Cerebral Small Vessel Diseases; Neuroinflammatory Diseases

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wei Wang, MD

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ke Shang, MD

CONTACT

86-27-83663337; kay_sang@qq.com

Ke Shang, MD

CONTACT

86-27-83663332; kay_sang@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, President of Tongji Hospital

Study Record Dates

• First Submitted: June 2, 2024
• First Posted: June 25, 2024
• Study Start: August 8, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 20, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)