Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease (CBSinIIDD)

NCT06474520 | Recruiting

• 1 other identifier: CBSinIIDD
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

According to the records of traditional Chinese medicine, CBS has the following functions: clearing the heart, resolving phlegm, promoting bile secretion, and calming the nerves. It can treat fever, coma, delirium, epilepsy, convulsions in children, dental caries, throat swelling, oral sores, carbuncle, and furuncle. The significant pathophysiological process of primary inflammatory demyelinating disease of the central nervous system (hereinafter referred to as IIDD) is the activation of the immune system of the central nervous system and the enhancement of inflammation. It includes several common diseases: multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-related disease (MOGAD), acute disseminated encephalomyelitis (ADEM), concentric sclerosis, tumor-like inflammatory demyelinating disease, etc. Combined with the inspiration brought to us by the above background research, especially bilirubin and bile acid are closely related to intestinal digestive function, and CBS is clinically effective through oral administration by subjects, the investigators speculate that CBS is likely to exert its immune, anti-inflammatory and neuroprotective effects on the brain by changing the intestinal flora and regulating the brain-gut axis. In terms of symptoms, CBS is likely to have the effect of improving the clinical symptoms of IIDD subjects and reducing disability.

Conditions

Idiopathic Inflammatory Demyelinating Disease; Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorder; Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease; Acute Disseminated Encephalomyelitis

Outcome Measures

Primary Outcomes (3)

• The Modified Rankin Scale (mRS)

  To assess mRS of subjects within 12 weeks after treatment initiation. The score ranges from 0 to 5. 5 represents the worst.

  Up to 12 weeks after treatment initiation

• Expanded Disability Status Scale (EDSS)

  To assess EDSS of subjects within 12 weeks after treatment initiation. The score ranges from 0 to 10. 10 represents the worst.

  Up to 12 weeks after treatment initiation

• Incidence and Severity of Adverse Effects (AEs) and Severe Adverse Effects (SAEs)

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

  Up to 14 weeks after treatment initiation

Secondary Outcomes (9)

• The number of newly increased inflammatory lesions 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 newly increased inflammatory lesions on gadolinium-enhanced T1 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

• Quantitative and qualitative changes in Montreal cognitive assessment scale (MoCA) 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

Other Outcomes (4)

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

  Up to 12 weeks after treatment initiation

• Quantitative and qualitative changes in 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 IIDD cohort

EXPERIMENTAL

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

Drug: Calculus bovis sativus (CBS)

Control therapy: no intervention, in IIDD cohort.

NO INTERVENTION

Subjects in IIDD 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 IIDD 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:

• IIDD cohort:
• Subjects are capable of understanding the purpose and risks of the study, providing informed consent and authorizing 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 18-65 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 Multiple sclerosis, meet the 2017 revised McDonald criteria, and enter the MS cohort;
• ② Aquaporin Protein-4-positive (AQP4) neuromyelitis optica spectrum disease, meet the 2015 international consensus diagnostic criteria for neuromyelitis optica spectrum disease (NMOSD), and AQP4 antibody positive, enter the AQP4-NMOSD cohort;
• ③ Myelin oligodendrocyte glycoprotein antibody-related disease, clinically diagnosed as MOGAD according to the 2023 international MOGAD diagnostic criteria, and positive MOG autoantibody test by cell-based-assay method;
• ④ Acute disseminated encephalomyelitis, clinically diagnosed as ADEM according to the 2013 International Pediatric Multiple Sclerosis Study Group (IPMSSG) diagnostic criteria, characterized by multifocal neurological deficits, must have encephalopathy manifestations (behavioral changes and/or changes in consciousness that cannot be explained by fever, including irritability), and exclude other specific antibody-positive IIDD.
• EDSS score ≤ 4 points at baseline (visit 1).
• Stable neurological examination within 30 days prior to 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:

• 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)
• Other causes of symptoms, including central nervous system 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).
• 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.

Sponsors & Collaborators

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

Study Sites (1)

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

Wuhan, Hubei, 430000, China

RECRUITING

Related Publications (24)

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MeSH Terms

Conditions

Multiple Sclerosis; Neuromyelitis Optica; Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease; Encephalomyelitis, Acute Disseminated

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Leukoencephalopathies; Brain Diseases; Central Nervous System Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; 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

Study Record Dates

• First Submitted: June 3, 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 (1)