NCT07356765

Brief Summary

"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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
120

participants targeted

Target at P75+ for not_applicable schizophrenia

Timeline
Completed

Started Sep 2023

Geographic Reach
1 country

1 active site

Status
enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 26, 2023

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2026

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

January 13, 2026

Completed
8 days until next milestone

First Posted

Study publicly available on registry

January 21, 2026

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2026

Completed
Last Updated

January 27, 2026

Status Verified

January 1, 2026

Enrollment Period

2.3 years

First QC Date

January 13, 2026

Last Update Submit

January 25, 2026

Conditions

Negative Symptoms of SchizophreniaSchizophrenia

Keywords

schizophreniaNegative Symptoms of SchizophreniaberberineClinical efficacyMechanism of action

Outcome Measures

Primary Outcomes (2)

  • Change in the total score of the Scale for Assessment of Negative Symptoms (SANS)

    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.

    Baseline, week4, week8, week12

  • log50 of the cutaneous niacin flush

    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.

    Baseline, week4, week8, week12

Secondary Outcomes (7)

  • 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

  • +2 more secondary outcomes

Study Arms (2)

berberine group

EXPERIMENTAL
Drug: Berberine

control group

PLACEBO COMPARATOR
Drug: Placebo

Interventions

BerberineDRUG

Berberine 300 mg by mouth each dose# three times a day# plus any stable antipsychotic drug

Also known as: stable antipsychotic
berberine group
PlaceboDRUG

The placebo were matched to Berberine in shape, smell and colour and tablets were sealed in identical bottles

Also known as: stable antipsychotic
control group

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Tianjin Anding Hospital

Tianjin, China

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Berberine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Berberine AlkaloidsBenzylisoquinolinesAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-Ring

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2026

First Posted

January 21, 2026

Study Start

September 26, 2023

Primary Completion

January 1, 2026

Study Completion

April 30, 2026

Last Updated

January 27, 2026

Record last verified: 2026-01

Locations

CN(1)