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AzTrials

EncephalitisNCT06584045

Efficacy and Safety of Calculus Bovis Sativus (CBS) for Adult Encephalitis (CBSinEncephalitis)

A study testing Calculus bovis sativus (CBS) in people with Encephalitis and Encephalitis, Viral, run by Tongji Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Based on the records of traditional Chinese medicine, CBS has the functions of purifying the heart, eliminating phlegm, stimulating bile secretion, and soothing the nerves. It has the ability to alleviate fever, coma, delirium, epilepsy, convulsions in youngsters, dental caries, throat swelling, mouth ulcers… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
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
30 Sep 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

  • Subjects must meet the following eligibility criteria at screening to participate in this study.
  • 1.1 Inclusion criteria for subjects with autoimmune encephalitis (hereinafter referred to as AE) of all subtypes 1.1.1 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.
  • 1.1.2. Tumors or malignancies can be reasonably excluded before the baseline visit (randomization), and screening guidelines for thymoma, teratoma, and malignant tumors should be followed.
  • 1.1.3. Both men and women are welcome, and the age at the time of providing informed consent is 18-80 years old (inclusive).
  • 1.1.4. Meet the diagnosis of AE (according to the Chinese Autoimmune Encephalitis Diagnosis and Treatment Expert Consensus 2022 Edition): A. Clinical manifestations: acute or subacute onset (<3 months), with one or more of the following neurological and psychiatric symptoms or clinical syndromes.
  • a. Limbic system symptoms: recent memory loss, epileptic seizures, mental and behavioral abnormalities, one or more of the three symptoms.
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  • b. Encephalitis syndrome: clinical manifestations of diffuse or multifocal brain damage.
  • c. Clinical manifestations of involvement of the basal ganglia and/or diencephalon/hypothalamus.
  • d. Mental disorder, and the psychiatric specialist believes that it does not meet the non-organic disease.
  • Auxiliary examination: one or more of the following auxiliary examination findings, or combined with related tumors.
  • a. Abnormal cerebrospinal fluid: cerebrospinal fluid leukocytosis (>5×106/L), or cerebrospinal fluid cytology shows lymphocytic inflammation, or specific oligoclonal bands are positive.
  • b. Neuroimaging or electrophysiological abnormalities: MRI limbic system T2 or FLAIR abnormal signals, unilateral or bilateral, or other areas of T2 or FLAIR abnormal signals (excluding nonspecific white matter changes and stroke); or PET imaging limbic system hypermetabolism changes, or multiple cortical and/or basal ganglia hypermetabolism. Figure 1 shows the typical neuroimaging manifestations of AE patients. Abnormal electroencephalogram, manifested as focal epilepsy or epileptiform discharge (located in the temporal lobe or outside the temporal lobe), or diffuse or multifocal slow wave rhythm. In adult patients with anti-NMDAR encephalitis, abnormal delta brush waves (extreme delta brush) often correspond to prolonged hospitalization and poor prognosis.
  • c. Specific types of tumors associated with AE, such as limbic encephalitis combined with small cell lung cancer, anti-NMDAR encephalitis combined with ovarian teratoma.
  • Confirmatory experiments: positive anti-neuronal antibodies. Including NMDA-R, LGI-1, CASPR2, IgLON5, GABAA/BR, GlyR, AMPAR and axonal protein-3α and intracellular substance antibodies anti-Hu, anti-Ma2, anti-CRMP5, anti-Yo, anti-double carrier protein, anti-GAD, etc.
  • Reasonably exclude other causes (refer to the differential diagnosis section of the consensus).
  • Diagnostic criteria: including possible AEs and confirmed AEs:
  • Possible AEs: meet the three diagnostic criteria of A, B and D.
  • Confirmed AEs: meet the four diagnostic criteria of A, B, C and D. 1.1.5. AE symptoms occurred ≤9 months before randomization 1.1.6. Subjects meet new AEs
  • New onset: defined as subjects with NMDA-R or LGI-1 AEs and meeting the following criteria:
  • The mRS score measured at baseline is stable (at least 24 hours) and is ≥2 points.
  • Received the first acute first-line treatment within 6 weeks before randomization (baseline visit).
  • 1.1.7. All females of childbearing potential and all males must use contraception 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.
  • 1.1.8. Stable neurological examination within 30 days before baseline (Visit 1).
  • 1.2 Additional inclusion criteria for the NMDA-R AE cohort
  • In addition to the criteria outlined in Section 1.1, only subjects who met all of the following criteria were eligible for inclusion in the NMDA-R AE cohort:
  • Age ≥ 18 years at the time of informed consent
  • Informed consent, as appropriate based on patient age, specific site, and national criteria
  • Suspected or definite NMDAR AE diagnosis as follows:
  • 1.2.1. Suspected NMDAR encephalitis was diagnosed when all three of the following criteria were met: 1.2.1.1 Rapid onset (less than 3 months) of at least four of the following six cardinal symptoms:
  • Abnormal (psychiatric) behavior or cognitive dysfunction
  • Speech dysfunction (rushing speech, hypospeech, mutism)
  • Seizures
  • Ataxia, dyskinesia, or rigid/abnormal posture
  • Decreased level of consciousness
  • Autonomic dysfunction or central hypoventilation 1.2.1.2. At least one of the following laboratory results:
  • Abnormal EEG (focal or diffuse slow or disorganized activity, epileptic activity, or extreme delta brushes)
  • CSF with pleocytosis or oligoclonal bands 1.2.1.3. Reasonable exclusion of other etiologies and other clear encephalitis syndromes: for example, Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary angiitis of the central nervous system (CNS), Rasmussen encephalitis.
  • Note: If the above three groups of symptoms in criterion 1.2.1.1 are present and accompanied by systemic teratoma, suspected NMDAR encephalitis can also be diagnosed.
  • 1.2.2 Definite NMDAR encephalitis can be diagnosed when the following three criteria are met at the same time: 1.2.2.1. The presence of one or more of the six main symptoms described in criterion 1.2.1.1 for suspected NMDAR encephalitis.
  • 1.2.2.2. History of anti-NMDAR (GluN1) IgG antibodies detected in CSF using a cell-based assay.
  • 1.2.3. Reasonable exclusion of other etiologies and other well-defined encephalitis syndromes: e.g., Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary angiitis of the central nervous system (CNS), Rasmussen encephalitis.
  • 1.3 Other inclusion criteria for the LGI-1 AE cohort
  • In addition to the criteria outlined in Section 1.1, only subjects who meet all of the following criteria are eligible for inclusion in the LGI1 AE cohort:
  • 1.3.1 Age ≥ 18 years at the time of signing the informed consent For subjects who are unable to provide informed consent due to the severity of their illness, the informed consent may be signed by their legally authorized representative at the time of obtaining the subject's consent, according to local requirements.
  • 1.3.2 Diagnosis of LGI-1 AE
  • The diagnosis of LGI-1 encephalitis can be made when both of the following criteria are met:
  • 1.3.2.1 Documented history of anti-LGI-1 IgG antibodies (in serum or CSF) using a cell-based assay.
  • 1.3.2.2 Subacute onset (less than 4 months of development) of working memory deficits, seizures (including faciobrachial dystonic seizures), or psychiatric symptoms suggestive of limbic system involvement.
  • 1.3.2.3 Diagnosis of LGI1 AE is reasonable when other etiologies and other well-defined encephalitis syndromes are excluded: e.g., Bickerstaff brainstem encephalitis, acute disseminated encephalomyelitis, Hashimoto encephalopathy, primary CNS vasculitis, Rasmussen encephalitis.
  • 1.4 Other inclusion criteria for the AA AE cohort
  • In addition to the criteria outlined in Section 1.1, only subjects who meet all of the following criteria are eligible for inclusion in the AA AE cohort:
  • Aged ≥ 18 years at the time of signing the informed consent form For subjects who are unable to provide informed consent due to the severity of their illness, the informed consent form may be signed by their legally authorized representative when the subject agrees, according to local requirements.
  • Diagnosis of AA AE Meet the diagnosis of AE in 1.1, negative for anti-NMDA antibodies and anti-LGI-1 antibodies, and positive for at least one of the other anti-neuronal antibodies.
  • 1.5 Inclusion criteria for viral encephalitis (hereinafter referred to as VE) cohort
  • The following four conditions must be met simultaneously for diagnosis of VE:
  • Primary condition: altered mental status, including decreased level of consciousness, drowsiness, or abnormal mental behavior lasting ≥24 h; or new onset of epileptic seizure
  • Secondary condition: fever ≥38 °C (before or within 72 h after onset), or new focal manifestations of the nervous system, or cerebrospinal fluid leukocytes ≥5×10^6/L, or cerebrospinal fluid cytology showing lymphocytic inflammation, or imaging showing brain parenchymal lesions consistent with encephalitis, or abnormal electroencephalogram consistent with encephalitis
  • Confirmatory laboratory test: positive cerebrospinal fluid viral nucleic acid (polymerase chain reaction or metagenomic next-generation sequencing), or positive cerebrospinal fluid and/or serum antiviral antibody IgM
  • Reasonable exclusion of other causes
  • 1.6 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.
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  • 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.

Ke Shang, MD contact

86-27-83663337

kay_sang@qq.com

Ke Shang, MD contact

86-27-83663477

kay_sang@hust.edu.cn

China1 site, 1 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

    Recruiting

Other trials in China

About this study

Official title: An Open Label Clinical Trial to Evaluate the Efficacy and Safety of Calculus Bovis Sativus (CBS) for Adult Encephalitis

Based on the records of traditional Chinese medicine, CBS has the functions of purifying the heart, eliminating phlegm, stimulating bile secretion, and soothing the nerves. It has the ability to alleviate fever, coma, delirium, epilepsy, convulsions in youngsters, dental caries, throat swelling, mouth ulcers, carbuncle, and furuncle.

Encephalitis is a neurological condition characterized by widespread or multiple inflammation of brain tissue. The causes of encephalitis are many and can stem from infectious organisms or be induced by autoimmune reactions, the latter being referred to as autoimmune encephalitis (AE). The yearly occurrence rate of encephalitis is 12.6 per 100,000 individuals. Among these cases, approximately 40-50% are caused by infectious factors, whereas 20-30% are attributed to autoimmune encephalitis (AE). The development of viral encephalitis involves the direct invasion of brain tissue by the virus and the immune response of the body to viral antigens. The virus multiplies extensively, leading to the degeneration of neurons, necrosis, the proliferation of glial cells, and the infiltration of inflammatory cells. These severe tissue reactions can result in the formation of demyelinating lesions and damage to blood vessels and the areas surrounding them. Additionally, vascular lesions affect the circulation in the brain and worsen the damage to brain tissue. The development of AE involves several factors, including molecular mimicry, the activation of latent antigen epitopes, the spread of antigen epitopes, and the disruption of the innate immune system caused by persistent pathogen infection.

Read more

The mechanisms that are clearer can be summarized as follows: (1) Decrease in the number of receptors on the surface due to cross-linking and internalization: Anti-NMDAR antibodies have the ability to attach to NMDAR on the postsynaptic membrane, resulting in a reduction of NMDAR surface density through cross-linking and internalization. This reduction leads to a decrease in NMDAR-mediated current, which in turn causes learning and memory defects. (2) Protein-protein interaction disruption: Anti-LGI1 antibodies can disrupt the binding between LGI1 and ADAM23 on the presynaptic membrane and ADAM22 on the postsynaptic membrane. This disruption leads to a decrease in the density of anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).

According to the aforementioned background processes, along with the most recent research, there was a decrease in the abundance of gut flora in patients with AE. Transplanting the fecal bacteria of individuals with anti-NMDAR encephalitis into mice's intestines resulted in cognitive impairment in the animals. This indicates that the brain-gut axis may have a significant role in the development of anti-NMDAR encephalitis. From a clinical perspective, patients consume CBS orally in order to achieve its therapeutic benefits. The primary constituents, bilirubin and bile acid, have been documented to possess regulatory effects on the gut microbiota. Thus, we hypothesize that CBS is probable to have neuroprotective and anti-inflammatory impacts on the brain through alterations in the intestinal microbiota and regulation of the brain-gut connection. CBS is expected to decrease the occurrence of symptomatic seizures and enhance the patient's level of consciousness and cognitive abilities.

Being tested
Calculus bovis sativus (CBS)
Medical subject headings
Encephalitis, Encephalitis, Viral, Autoimmune Diseases of the Nervous System

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 groups in NCT06584045
Study groupRoleWhat they receive
CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in encephalitis cohortExperimentalSubjects in encephalitis cohort of this arm will receive general therapy plus CBS.
Receives: Drug: Calculus bovis sativus (CBS)
Control therapy: no intervention, in encephalitis cohortNo interventionSubjects in encephalitis cohort of this arm will only receive general therapy.
CBS therapy, CBS dosage: 100mg per day from day 1 to day 84, in healthy cohortExperimentalSubjects 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.

  1. 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

  2. Clinical Assessment Scale in Autoimmune Encephalitis (CASE)

    To assess CASE of subjects within 12 weeks after treatment initiation. The score ranges from 0 to 27. 27 represents the worst.

    Measured: Up to 12 weeks after treatment initiation

  3. 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 (10)

  1. 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

  2. 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

  3. The quantity of epileptiform abnormalities on electroencephalograph at week 12 compared with baseline (visit 1) and control group.

    Measured: Up to 12 weeks after treatment initiation

  4. The quantity of background deterioration on electroencephalograph at week 12 compared with baseline (visit 1) and control group.

    Measured: Up to 12 weeks after treatment initiation

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  1. First posted4 Sep 2024
  2. Study start30 Sep 2024
  3. Primary completionJul 2029 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06584045
Sponsor's protocol ID
CBSinEncephalitis
Status last verified
Apr 2025
First submitted
26 Aug 2024
Last updated
8 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chen H, Chen Z, Shen L, Wu X, Ma X, Lin D, Zhang M, Ma X, Liu Y, Wang Z, Zhang Y, Kuang Z, Lu Z, Li X, Ma L, Lin X, Si L, Chen X. Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice. Cell Death Discov. 2020 Aug 11;6:75. doi: 10.1038/s41420-020-00309-8. eCollection 2020.

    PubMed 32821439

  • 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 27880884

  • Zhou 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 37633621

  • Yu 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 32068140

  • Shi 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 26016891

  • Shimada 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 23392879

  • Li 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 34736706

  • Liu 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 25829769

  • Tang 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 36871364

  • Takahashi 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 20804621

  • Lu 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 32730869

  • Zhong 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 27616028

  • Vitek 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 34153399

  • Thakkar 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 30612336

  • Vasavda 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 31353321

Questions about this trial

What is this clinical trial studying?

A study testing Calculus bovis sativus (CBS) in people with Encephalitis and Encephalitis, Viral, 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 62 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 8 Apr 2025. 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 NCT06584045, which also lists 25 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 8 Apr 2025.

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