Idiopathic Inflammatory Demyelinating DiseaseNCT06474520
Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease (CBSinIIDD)
A study testing Calculus bovis sativus (CBS) in people with Idiopathic Inflammatory Demyelinating Disease and Multiple Sclerosis, run by Tongji Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Idiopathic Inflammatory Demyelinating Disease, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder
- What is being tested?
- Calculus bovis sativus (CBS)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteChina
- Study dates
- 8 Aug 2024to Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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;
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- 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
Who cannot join
- 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.
Show all 43Show fewer
- 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 corrected QT interval >450 msec (male) or 470 msec (female), where corrected QT interval is determined based on the Fridericia correction method, within 3 months prior to the screening visit.
- Planned elective procedures or surgeries at any time after signing the Informed Consent Form by follow-up visit.
- Any condition that affects the absorption of study treatment (e.g., gastrectomy).
- History of hypersensitivity to heparin or history of heparin-induced thrombocytopenia.
- Subjects with abnormalities in medical history, physical examination, ECG, or diagnostic laboratory tests that the investigator considers to be clinically relevant.
- History of human immunodeficiency virus (HIV) or positive test results at screening.
- Current infection with hepatitis C (defined as positive hepatitis C virus (HCV) antibodies and detectable HCV RNA). Subjects with positive HCV antibodies and HCV RNA below the limit of detection are eligible to participate in the study.
- Current infection with hepatitis B (defined as positive HBsAg and/or positive total anti-HBc).
- Chronic, recurrent, or severe infection (e.g., pneumonia, sepsis) within 90 days prior to baseline (visit 1).
- History of tuberculosis (TB) diagnosis or positive latent TB test result.
- Symptoms of bacterial, fungal, or viral infection (including upper respiratory tract infection) within 28 days prior to baseline (visit 1). Subjects with localized fungal infection (e.g., candidiasis, tinea) are eligible for rescreening after successful treatment of the infection.
- Infection requiring hospitalization or IV anti-infective medication within 4 weeks prior to baseline visit.
- Any live or live attenuated vaccine within 28 days prior to baseline (visit 1) or planned during the study.
- Contraindications to all of the following salvage therapies: rituximab, intravenous immunoglobulin, high-dose corticosteroids, or IV cyclophosphamide.
- History of or receipt of the following treatments: Total lymphoid irradiation, cladribine, T-cell or T Cell recipient vaccination, total body irradiation, or total lymphoid irradiation at any time. Stem cell transplantation at any time.
- Abnormal laboratory values determined by the investigator to be clinically significant at Screening or Baseline (Visit 1).
- Any of the following blood test abnormalities at Screening: a. White blood cell count < 3.0 × 10^3/µL. b. Absolute neutrophil count < 2.0 × 10^3/µL. c. Absolute lymphocyte count < 0.5 × 10^3/µL. d. Platelet count < × 10 × 10^4/µL. e. glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, or γ-glutamyl transpeptidase ≥ 3 x upper limit of normal (ULN) or bilirubin > 2 x ULN. f. glomerular filtration rate ≤ 60 mL/min/1.73 m2. g. Lymphocyte count < lower limit of normal
- Any of the following urine test abnormalities at Screening: a. β-2-microglobulin>0.3 μg/mL. b. Albumin/creatinine ratio>22.6 mg/mmol.
- Previous participation in this study.
- Blood donation (1 unit or more) within 90 days before screening, plasma donation within 1 week before screening, and platelet donation within 6 weeks before screening.
- History of alcohol or drug abuse in the past year (determined by the investigator).
- Pregnant or lactating subjects, as well as subjects planning to become pregnant or start breastfeeding at any time during the study and within 30 days after completion of study treatment.
- Participating in a clinical trial or having participated in a clinical trial within 90 days before screening.
- History of clinically significant suicidal thoughts or behaviors in the past 12 months as assessed by Columbia-Suicide Severity Rating Scale at screening.
- Unwilling or unable to comply with protocol requirements.
- The patient has obvious hearing or vision impairment, language barriers, claustrophobia, etc., which makes the patient unable to cooperate with the neuropsychological scale assessment and MRI examination.
- The researcher or sponsor believes that there are other unknown reasons that make the subject unsuitable for inclusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430000
Ke Shang, MD, 86-27-83663337, kay_sang@qq.com
Ke Shang, MD, 86-27-83663333, kay_sang@hust.edu.cn
About this study
Official title: An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease
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
- Being tested
- Calculus bovis sativus (CBS)
- Medical subject headings
- Multiple Sclerosis, Neuromyelitis Optica, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, Encephalomyelitis, Acute Disseminated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Calculus bovis sativus (CBS)Drug
Subjects will orally receive 100mg CBS per day from day 1 to day 84.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Calculus bovis sativus (CBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
The score of MMSE ranges from 0 to 30, and 30 represents the best.
Measured: 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.
Measured: 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.
The score of MoCA ranges from 0 to 30, and 30 represents the best.
Measured: Up to 12 weeks after treatment initiation
The score of Hamilton Anxiety Scale at week 12 compared with baseline (visit 1) and control group.
The score of Hamilton Anxiety Scale ranges from 0 to 56, and 56 represents the worst.
Measured: Up to 12 weeks after treatment initiation
The score of Hamilton Depression Scale at week 12 compared with baseline (visit 1) and control group.
The score of Hamilton Depression Scale ranges from 0 to 81, and 81 represents the worst.
Measured: 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.
The score of SF-36 ranges from 0 to 100, and 100 represents the best.
Measured: 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.
Measured: Up to 14 weeks after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2024
- Study start8 Aug 2024
- Primary completionJul 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Inflammatory Demyelinating DiseaseStudies of the same condition, open and under way.
- More trials run by Tongji HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Jianmin Pharmaceutical Group Co., LTD.
- Responsible party
- Principal investigator, Wei Wang, Tongji Hospital
- Investigators
- Wei Wang, MD, Principal investigator, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06474520
- Sponsor's protocol ID
- CBSinIIDD
- Status last verified
- Sep 2024
- First submitted
- 3 Jun 2024
- Last updated
- 20 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fu WJ, Lei T, Yin Z, Pan JH, Chai YS, Xu XY, Yan YX, Wang ZH, Ke J, Wu G, Xu RH, Paranjpe M, Qu L, Nie H. Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis. J Ethnopharmacol. 2017 Jan 4;195:118-126. doi: 10.1016/j.jep.2016.11.015. Epub 2016 Nov 20.
PubMed 27880884Zhou J, Jiang T, Wang J, Wu W, Duan X, Jiang H, Jiao Z, Wang X. Multimodal investigation reveals the neuroprotective mechanism of Angong Niuhuang pill for intracerebral hemorrhage: Converging bioinformatics, network pharmacology, and experimental validation. J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117045. doi: 10.1016/j.jep.2023.117045. Epub 2023 Aug 24.
PubMed 37633621Yu ZJ, Xu Y, Peng W, Liu YJ, Zhang JM, Li JS, Sun T, Wang P. Calculus bovis: A review of the traditional usages, origin, chemistry, pharmacological activities and toxicology. J Ethnopharmacol. 2020 May 23;254:112649. doi: 10.1016/j.jep.2020.112649. Epub 2020 Feb 14.
PubMed 32068140Shi Y, Xiong J, Sun D, Liu W, Wei F, Ma S, Lin R. Simultaneous quantification of the major bile acids in artificial Calculus bovis by high-performance liquid chromatography with precolumn derivatization and its application in quality control. J Sep Sci. 2015 Aug;38(16):2753-62. doi: 10.1002/jssc.201500139. Epub 2015 Jun 30.
PubMed 26016891Shimada K, Azuma Y, Kawase M, Takahashi T, Schaffer SW, Takahashi K. Taurine as a marker for the identification of natural Calculus Bovis and its substitutes. Adv Exp Med Biol. 2013;776:141-9. doi: 10.1007/978-1-4614-6093-0_15.
PubMed 23392879Li X, Yao Y, Chen M, Ding H, Liang C, Lv L, Zhao H, Zhou G, Luo Z, Li Y, Zhang H. Comprehensive evaluation integrating omics strategy and machine learning algorithms for consistency of calculus bovis from different sources. Talanta. 2022 Jan 15;237:122873. doi: 10.1016/j.talanta.2021.122873. Epub 2021 Sep 30.
PubMed 34736706Liu Y, Tan P, Liu S, Shi H, Feng X, Ma Q. A new method for identification of natural, artificial and in vitro cultured Calculus bovis using high-performance liquid chromatography-mass spectrometry. Pharmacogn Mag. 2015 Apr-Jun;11(42):304-10. doi: 10.4103/0973-1296.153083.
PubMed 25829769Tang Y, Han Z, Zhang H, Che L, Liao G, Peng J, Lin Y, Wang Y. Characterization of Calculus bovis by principal component analysis assisted qHNMR profiling to distinguish nefarious frauds. J Pharm Biomed Anal. 2023 May 10;228:115320. doi: 10.1016/j.jpba.2023.115320. Epub 2023 Mar 1.
PubMed 36871364Takahashi K, Azuma Y, Shimada K, Saito T, Kawase M, Schaffer SW. Quality and safety issues related to traditional animal medicine: role of taurine. J Biomed Sci. 2010 Aug 24;17 Suppl 1(Suppl 1):S44. doi: 10.1186/1423-0127-17-S1-S44.
PubMed 20804621Lu F, Wang L, Chen Y, Zhong X, Huang Z. In vitro cultured calculus bovis attenuates cerebral ischaemia-reperfusion injury by inhibiting neuronal apoptosis and protecting mitochondrial function in rats. J Ethnopharmacol. 2020 Dec 5;263:113168. doi: 10.1016/j.jep.2020.113168. Epub 2020 Jul 27.
PubMed 32730869Zhong XM, Ren XC, Lou YL, Chen MJ, Li GZ, Gong XY, Huang Z. Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats. J Ethnopharmacol. 2016 Nov 4;192:390-397. doi: 10.1016/j.jep.2016.09.014. Epub 2016 Sep 9.
PubMed 27616028Vitek L, Tiribelli C. Bilirubin: The yellow hormone? J Hepatol. 2021 Dec;75(6):1485-1490. doi: 10.1016/j.jhep.2021.06.010. Epub 2021 Jun 18.
PubMed 34153399Thakkar M, Edelenbos J, Dore S. Bilirubin and Ischemic Stroke: Rendering the Current Paradigm to Better Understand the Protective Effects of Bilirubin. Mol Neurobiol. 2019 Aug;56(8):5483-5496. doi: 10.1007/s12035-018-1440-y. Epub 2019 Jan 5.
PubMed 30612336Vasavda C, Kothari R, Malla AP, Tokhunts R, Lin A, Ji M, Ricco C, Xu R, Saavedra HG, Sbodio JI, Snowman AM, Albacarys L, Hester L, Sedlak TW, Paul BD, Snyder SH. Bilirubin Links Heme Metabolism to Neuroprotection by Scavenging Superoxide. Cell Chem Biol. 2019 Oct 17;26(10):1450-1460.e7. doi: 10.1016/j.chembiol.2019.07.006. Epub 2019 Jul 25.
PubMed 31353321Liu HW, Gong LN, Lai K, Yu XF, Liu ZQ, Li MX, Yin XL, Liang M, Shi HS, Jiang LH, Yang W, Shi HB, Wang LY, Yin SK. Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage. Neuron. 2023 May 17;111(10):1609-1625.e6. doi: 10.1016/j.neuron.2023.02.022. Epub 2023 Mar 14.
PubMed 36921602
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Idiopathic Inflammatory Demyelinating Disease
- ClinicalTrials.gov ID
- NCT06474520
- Acronym / sponsor ID
- CBSinIIDD
- Conditions
- Idiopathic Inflammatory Demyelinating Disease, Multiple Sclerosis, Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Acute Disseminated Encephalomyelitis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Collaborators
- Jianmin Pharmaceutical Group Co., LTD.
- Study start
- 8 Aug 2024 (actual)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 25 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in IIDD cohort | Experimental | Drug: Calculus bovis sativus (CBS)Subjects in IIDD cohort of this arm will receive general therapy plus 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 | Drug: Calculus bovis sativus (CBS)Subjects in healthy cohort of this arm will only receive CBS. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- IIDD cohort:
- 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.
Key exclusion criteria (43 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Calculus bovis sativus (CBS)Subjects will orally receive 100mg CBS per day from day 1 to day 84. | Drug | 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 |
Primary outcome
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. The score ranges from 0 to 5. 5 represents the worst.
Expanded Disability Status Scale (EDSS)
Time frame: Up to 12 weeks after treatment initiation
To assess EDSS of subjects within 12 weeks after treatment initiation. The score ranges from 0 to 10. 10 represents the worst.
Incidence and Severity of Adverse Effects (AEs) and Severe Adverse Effects (SAEs)
Time frame: Up to 14 weeks after treatment initiation
To evaluate the AEs and SAEs occurred within 14 weeks after treatment initiation
9 secondary outcomes
The number of newly increased inflammatory lesions on T2 flair weighted imaging at week 12 compared with baseline (visit 1) and control group.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 weeks after treatment initiation
The score of Hamilton Anxiety Scale at week 12 compared with baseline (visit 1) and control group.
Time frame: Up to 12 weeks after treatment initiation
The score of Hamilton Depression Scale at week 12 compared with baseline (visit 1) and control group.
Time frame: 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.
Time frame: 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.
Time frame: Up to 14 weeks after treatment initiation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
- Background: PubMed 27880884Fu WJ, Lei T, Yin Z, Pan JH, Chai YS, Xu XY, Yan YX, Wang ZH, Ke J, Wu G, Xu RH, Paranjpe M, Qu L, Nie H. Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis. J Ethnopharmacol. 2017 Jan 4;195:118-126. doi: 10.1016/j.jep.2016.11.015. Epub 2016 Nov 20.
- Background: PubMed 37633621Zhou J, Jiang T, Wang J, Wu W, Duan X, Jiang H, Jiao Z, Wang X. Multimodal investigation reveals the neuroprotective mechanism of Angong Niuhuang pill for intracerebral hemorrhage: Converging bioinformatics, network pharmacology, and experimental validation. J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117045. doi: 10.1016/j.jep.2023.117045. Epub 2023 Aug 24.
- Background: PubMed 32068140Yu ZJ, Xu Y, Peng W, Liu YJ, Zhang JM, Li JS, Sun T, Wang P. Calculus bovis: A review of the traditional usages, origin, chemistry, pharmacological activities and toxicology. J Ethnopharmacol. 2020 May 23;254:112649. doi: 10.1016/j.jep.2020.112649. Epub 2020 Feb 14.
- Background: PubMed 26016891Shi Y, Xiong J, Sun D, Liu W, Wei F, Ma S, Lin R. Simultaneous quantification of the major bile acids in artificial Calculus bovis by high-performance liquid chromatography with precolumn derivatization and its application in quality control. J Sep Sci. 2015 Aug;38(16):2753-62. doi: 10.1002/jssc.201500139. Epub 2015 Jun 30.
- Background: PubMed 23392879Shimada K, Azuma Y, Kawase M, Takahashi T, Schaffer SW, Takahashi K. Taurine as a marker for the identification of natural Calculus Bovis and its substitutes. Adv Exp Med Biol. 2013;776:141-9. doi: 10.1007/978-1-4614-6093-0_15.
- Background: PubMed 34736706Li X, Yao Y, Chen M, Ding H, Liang C, Lv L, Zhao H, Zhou G, Luo Z, Li Y, Zhang H. Comprehensive evaluation integrating omics strategy and machine learning algorithms for consistency of calculus bovis from different sources. Talanta. 2022 Jan 15;237:122873. doi: 10.1016/j.talanta.2021.122873. Epub 2021 Sep 30.
- Background: PubMed 25829769Liu Y, Tan P, Liu S, Shi H, Feng X, Ma Q. A new method for identification of natural, artificial and in vitro cultured Calculus bovis using high-performance liquid chromatography-mass spectrometry. Pharmacogn Mag. 2015 Apr-Jun;11(42):304-10. doi: 10.4103/0973-1296.153083.
- Background: PubMed 36871364Tang Y, Han Z, Zhang H, Che L, Liao G, Peng J, Lin Y, Wang Y. Characterization of Calculus bovis by principal component analysis assisted qHNMR profiling to distinguish nefarious frauds. J Pharm Biomed Anal. 2023 May 10;228:115320. doi: 10.1016/j.jpba.2023.115320. Epub 2023 Mar 1.
- Background: PubMed 20804621Takahashi K, Azuma Y, Shimada K, Saito T, Kawase M, Schaffer SW. Quality and safety issues related to traditional animal medicine: role of taurine. J Biomed Sci. 2010 Aug 24;17 Suppl 1(Suppl 1):S44. doi: 10.1186/1423-0127-17-S1-S44.
- Background: PubMed 32730869Lu F, Wang L, Chen Y, Zhong X, Huang Z. In vitro cultured calculus bovis attenuates cerebral ischaemia-reperfusion injury by inhibiting neuronal apoptosis and protecting mitochondrial function in rats. J Ethnopharmacol. 2020 Dec 5;263:113168. doi: 10.1016/j.jep.2020.113168. Epub 2020 Jul 27.
- Background: PubMed 27616028Zhong XM, Ren XC, Lou YL, Chen MJ, Li GZ, Gong XY, Huang Z. Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats. J Ethnopharmacol. 2016 Nov 4;192:390-397. doi: 10.1016/j.jep.2016.09.014. Epub 2016 Sep 9.
- Background: PubMed 34153399Vitek L, Tiribelli C. Bilirubin: The yellow hormone? J Hepatol. 2021 Dec;75(6):1485-1490. doi: 10.1016/j.jhep.2021.06.010. Epub 2021 Jun 18.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wei Wang, MD principal investigator
Tongji Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Calculus bovis sativus (CBS) in people with Idiopathic Inflammatory Demyelinating Disease and Multiple Sclerosis, run by Tongji Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ke Shang, MD (86-27-83663337, kay_sang@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Modified Rankin Scale (mRS) (time frame: Up to 12 weeks after treatment initiation). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06474520, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2024.