Berberine in Treating Negative Symptoms of Schizophrenia: Clinical Efficacy and Mechanisms
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Change in the total score of the Scale for Assessment of Negative Symptoms (SANS)
研究概览
简要总结
"Negative" symptoms are a major challenge for people with schizophrenia (SZ) and are a key reason why they struggle with everyday functioning. While current medications work well for the "positive" symptoms (like hallucinations or delusions), they aren't very effective at improving these "negative" symptoms, which include things like a lack of motivation or emotion. This study plans to conduct a large, randomized, double-blind, placebo-controlled trial to see if a compound called berberine (BBR) can safely and effectively improve these negative symptoms in SZ. The investigators will also examine how BBR affects gut bacteria, their byproducts in stool, and levels of general inflammation in the body. By looking at these different biological markers before and after BBR treatment, the investigators aim to understand how BBR influences negative symptoms and identify its main targets for improvement. This could lead to new ways to treat negative symptoms in schizophrenia in the future.
详细描述
The investigators will enroll at least 120 patients with schizophrenia (SZ) meeting the inclusion criteria, randomized 1:1 to either the experimental group receiving antipsychotic medication plus berberine (BBR) or the control group receiving antipsychotic medication plus placebo, for a clinical intervention of 12 weeks. The primary outcome measures will be the change in the Negative Symptom Scale (SANS) total score and the log50 result of the skin nicotine test throughout the 12-week period. Secondary outcome measures include the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI), the Calgary Depression Scale for Schizophrenia (CDSS), the Global Assessment of Functioning (GAF), the Extrapyramidal Symptom Rating Scale, and cognitive assessments (MATRICS Consensus Cognitive Battery - MCCB). Other study indicators will involve the collection of sociodemographic and general clinical data. Blood and stool samples will be collected at pre-intervention (baseline), at 12 weeks of intervention, or at study termination. For safety assessments, participants' vital signs will be monitored at baseline, 4 weeks, 8 weeks, and 12 weeks, along with physical parameters (height, weight, blood pressure). Laboratory investigations will include complete blood count, comprehensive biochemical panel, and electrocardiogram (ECG). The Treatment Emergent Symptom Scale (TESS) will be used to assess drug side effects, and any adverse events will be recorded. Ultimately, the collected data will be used to investigate the clinical efficacy and safety of BBR on negative symptoms in SZ, its impact on the gut microbiota and their metabolic small molecules, its effect on peripheral blood inflammatory factors in SZ patients, and the longitudinal and cross-sectional correlations between gut microbiota and their metabolic small molecules, blood parameters, and negative symptoms in SZ patients under BBR treatment. This will facilitate the identification of early predictive biomarkers for BBR efficacy and key gut microbiota targets responsible for improving negative symptoms in SZ.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The diagnosis was confirmed by two psychiatrists who interviewed enrolled patients using the Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV).
- •Age between 18 and 60 years, inclusive.
- •Gender: Not restricted.
- •Ethnicity: Han Chinese.
- •Subjects were receiving a stable dose of antipsychotic medication for at least 3 months prior to enrollment and had no dose adjustments in the month preceding enrollment.
- •Subjects exhibited significant negative symptoms, defined as: A total score of ≤ 70 on the Positive and Negative Syndrome Scale (PANSS). Scores of ≤ 4 on the PANSS items for delusions, conceptual disorganization, hallucinations, and excitement. A score > 0 on the Negative Symptom Subscale-Positive Symptom Subscale.
- •The patient or their legal representative provided informed consent and signed the informed consent form agreeing to participate in the study.
排除标准
- •Individuals meeting DSM-5 criteria for other psychiatric disorders.
- •Current severe neurological disease, uncontrolled metabolic disease, infectious disease, or autoimmune disease.
- •History of gastrointestinal surgery.
- •Use of antibiotics, other immunomodulatory agents, hormones, microecological agents, or probiotic medications within the past 1 month.
- •Allergy to BBR (if "BBR" is a known abbreviation, otherwise it should be spelled out or defined).
- •Receipt of physical therapies such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the past 1 month.
- •Individuals with hemolytic anemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- •Pregnant or lactating females.
- •Any factor that would prevent the participant from providing informed consent or participating in the study.
研究组 & 干预措施
berberine group
干预措施: Berberine (Drug)
control group
干预措施: Placebo (Drug)
结局指标
主要结局
Change in the total score of the Scale for Assessment of Negative Symptoms (SANS)
时间窗: Baseline, week4, week8, week12
The Scale for Assessment of Negative Symptoms (SANS) is a clinician-rated observational scale developed by American neuropsychiatrist Nancy C. Andreasen to assess negative symptoms in schizophrenia. The scale includes categories such as alogia (poverty of speech), blunted affect, avolition, anhedonia/asociality, and attention impairment, with a focus on evaluating the patient's deficit symptoms of mental activity. Changes in the total SANS score will, to a certain extent, reflect changes in the severity of the subject's negative symptoms.
log50 of the cutaneous niacin flush
时间窗: Baseline, week4, week8, week12
In this study, the Skin Flush Meter will be utilized for the first time to quantify the attenuation of the niacin flush response, serving as an objective assessment tool for negative symptoms in schizophrenia (SZ). Building upon a pre-existing image library of niacin flush responses from a previous cohort, the research team from our collaborating unit has developed a niacin predictor device. This device largely preserves the observational steps of the original method. Based on this, previously manual simple scoring has been replaced with artificial intelligence (AI) for processing large volumes of color images. It compares pre- and post-niacin color differences in the skin, extracts variables for erythema intensity, and precisely calculates the area of irregular redness. By integrating the temporal dimension, it further achieves quantification and refinement with second-level resolution.
次要结局
- Cognitive Function(Baseline, week4, week8, week12)
- Psychiatric Symptoms(Baseline, week4, week8, week12)
- Clinical efficacy(Baseline, week4, week8, week12)
- Depressive Symptoms(Baseline, week4, week8, week12)
- Functional capacity(Baseline, week4, week8, week12)
- Changes of CRP(Baseline, week12)
- Fecal 16S rRNA sequencing(Baseline, week12)