Berberine Improving Cognitive Impairments in Schizophrenia

Study on the Mechanism s of Berberine Improving Cognitive Impairments in Schizophrenia Based on "Gut m Icrobiota-gut-brain"Axis

The study was a 12-week, randomized, double-blind, placebo-controlled trial. Berberine (300 mg, three times a day) has been used as an auxiliary treatment on the basis of stable antipsychotic treatment. All participants were randomly divided into two groups.Any stable antipsychotic + berberine(BBR) or any stable antipsychotic +placebo. Positive and Negative Syndrome Scale (PANSS) has been used for psychiatric symptoms. MATRICS Consensus Cognitive Battery（MCCB）has been used for cognitive symptoms. The treatment Emergent Symptom Scale(TESS) has been used for evaluate adverse effects. Plasma Metabolomics, Inflammatory Factors, BDNF, fecal Macrogene Sequencing, and fecal Metabolomics were obtained at 0, 4,8 ,12weeks.

Study Overview

• Status: Enrolling by invitation
• Conditions: Schizophrenia Therapeutics
• Intervention / Treatment: Drug: Placebo; Drug: Berberine

Detailed Description

Plasma Metabolomics, Inflammatory Factors, BDNF, fecal Macrogene Sequencing, and fecal Metabolomics were obtained at 0, 4,8 ,12weeks.

Inflammatory factors:C-reaction protein(CRP),Interleukine-1 beta(IL-1β), Interleukine-6 (IL-6), Tumor necrosis factor-α (TNF-α).

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Tianjin Anding Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals who aged 18 to 60 years
• Meet the diagnosis of schizophrenia according to DSM-V
• Treatment with stable Antipsychotic ≥ 3 months, and the drug dose was not adjusted 1 month before enrollment
• The total score of the Positive and Negative Syndrome Scale (PANSS) ≤ 70 points, with scores of item delusion, conceptual confusion, hallucination, and excitement ≤ 4 points
• The MATRICS Conscience Cognitive Battery for Schizophrenia,MCCB) scoring defect score ≥ 3 points
• Gender unlimited
• Sign the informed consent form

Exclusion Criteria:

• Individuals who with diagnosis of other psychiatric disorders except schizophrenia according to DSM-V
• Refused to provide informed consent
• Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases
• Currently on anti-inflammatory or immunosuppressant medication including oral steroids and history of chronic infection (including tuberculosis, HIV and hepatitis), malignancy, organ transplantation, blood dyscrasia, central nervous system demyelinating disorder, and any other known autoimmune or inflammatory condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: control group	Drug: Placebo; The placebo were matched to Berberine in shape, smell and colour and tablets were sealed in identical bottles; Other Names: stable antipsychotic
Experimental: berberine group	Drug: Berberine; Berberine 300mg#three times a day# plus any stable antipsychotic drug; Other Names: stable antipsychotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of cogination symptoms	MCCB is a standardized measurement tool for assessing cognitive function in schizophrenia. There are 9 subtests, which mainly assess 7 cognitive domains, including information processing speed, attention/alertness, Working memory, word learning, visual memory, reasoning and problem solving, and social cognition. After the evaluation is completed, the MCCB rough score is converted into the total score T score obtained after correction for age, gender, years of education, and untreated period. The T score is then converted into a defect score, with T scores ≥ 40, 35-39, 30-34, 25-29, 20-24, and ≤ 19 corresponding to defect scores 0, 1, 2, 3, 4, and 5, respectively. Among them, 1 represents mild defects, 2 represents mild to moderate defects, 3 represents moderate defects, 4 represents moderate to severe defects, and 5 represents severe defects. In this study, a defect score of ≥ 3 was used as the boundary for significant cognitive impairment.	changes within 0,4,8,12weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of CRP	The concentration of C-reactive protein (CRP) is measured in venous blood. CRP is an acute-phase reactant protein synthesized by the liver, primarily functioning to recognize and clear pathogens or damaged cells. It plays a crucial role in inflammatory responses, infection surveillance, and disease monitoring.	changes within 0, 4, 8, 12weeks
Changes of Plasma Metabolomics(PM)	Collected and stored plasma samples were registered in the MetLIMS software, including relevant sample information. Subsequently, these samples underwent mass spectrometry-based detection and quantification. Each sample was divided into two aliquots for analysis: the first aliquot was subjected to Flow Injection Analysis (FIA) mode for signal acquisition, and the second aliquot was analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) mode. The resultant data were imported into the Biocrates MetIDQ™ software for the precise calculation of analyte concentrations and comprehensive data evaluation. Further analysis was conducted utilizing the MetaboAnalyst 5.0 platform, along with resources such as the KEGG database, to identify significant metabolites and explore associated metabolic pathways.	changes within 0, 12weeks
Changes of IL-1β	The levels of IL-1β has been obtained at 4 point intervals: 0, 4, 8,12 weeks	changes within 0,4,8,12weeks
Changes of IL-6	The levels of IL-6 has been obtained at 4 point intervals: 0, 4, 8 ,12weeks	changes within 0,4,8,12weeks
Changes of TNF-α	The levels of TNF-α has been obtained at 4 point intervals: 0, 4, 8 ,12weeks	changes within 0,4,8,12weeks
Changes of BDNF	The levels of BDNF has been obtained at 4 point intervals: 0, 4, 8,12 weeks	changes within 0,4,8,12weeks
Changes of Fecal Macrogene Sequencing(FMS)	Total genomic DNA was extracted from patient fecal samples and subjected to quality control. Qualified DNA was then randomly fragmented to approximately 350 bp using a Covaris ultrasonic disruptor to generate libraries, which were quantified by Qubit and qPCR. Following library QC, pooled libraries were sequenced on an Illumina NovaSeq platform (PE150). Raw sequencing data underwent quality control, followed by assembly and gene prediction to construct a non-redundant gene set. Genes were then annotated for taxonomic and functional classification and abundance statistics were computed. Statistical analyses, including similarity clustering, group ordination, and differential comparisons, were performed on samples and sample groups.	changes within 0, 12weeks
Changes of Fecal Metabolomics(FM)	Collected and stored patient fecal samples were registered in the MetLIMS software, including relevant sample information. Subsequently, these samples underwent mass spectrometry-based detection and quantification. Each sample was divided into two aliquots for analysis: the first aliquot was subjected to Flow Injection Analysis (FIA) mode for signal acquisition, and the second aliquot was analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) mode. Data Processing and Pathway Analysis: The resultant data were imported into the Biocrates MetIDQ™ software for the precise calculation of analyte concentrations and comprehensive data evaluation. Further analysis was conducted utilizing the MetaboAnalyst 5.0 platform, along with resources such as the KEGG database, to identify significant metabolites and explore associated metabolic pathways.	changes within 0, 12weeks

Collaborators and Investigators

• Sponsor: Tianjin Anding Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Estimated): July 23, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: July 22, 2023
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; Intestinal flora; berberine; cognitive symptoms
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Schizophrenia; Neurobehavioral Manifestations; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Benzylisoquinolines; Berberine Alkaloids; Berberine
• Other Study ID Numbers: BBR-SCH-2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No