Schizophrenia Therapeutics
Conditions
Keywords
schizophrenia, berberine, cognitive symptoms, Intestinal flora
Brief summary
This study is a 12-week, randomized, blank-controlled, assessor-blinded trial. Eligible patients were randomized in a 1:1 ratio to receive either berberine hydrochloride or blank control as an add on to their stable antipsychotic regimen for 12 weeks. Randomization was performed using a computer-generated random number table, and allocation was concealed using sequentially numbered, opaque, sealed envelopes. The trial included four visits: baseline (visit 1), week 4 (visit 2), week 8 (visit 3) and week 12 (visit 4). Patients in the berberine group received berberine hydrochloride tablets (100 mg/tablet), three tablets three times daily. The control group received no intervention (blank control) and continued their usual care.
Detailed description
Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS); cognitive symptoms were evaluated using the MATRICS Consensus Cognitive Battery (MCCB); depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24); and anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAMA). All assessments were administered by trained research personnel. The MCCB assessment was performed only at baseline and Week 12, whereas the PANSS, HAMD, and HAMA assessments were conducted at baseline, Week 4, Week 8, and Week 12. The primary outcome measure was the uncorrected T-score of the MCCB Overall Composite Score, which was derived by standardizing and summing the T-scores across seven cognitive domains: processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Since commercially available berberine is only formulated as yellow tablets with a marked bitter taste, which makes it difficult to prepare an indistinguishable placebo, a blank control design was adopted to maintain feasibility while ensuring the integrity of the study. We acknowledge that this open-label design may introduce potential placebo effects. Nevertheless, the cognitive assessments are less susceptible to expectancy effects, and both the raters and statisticians were blinded to group assignment to minimize bias.
Interventions
DRUGBerberine
Patients in the berberine group received berberine hydrochloride tablets (100 mg/tablet), three tablets three times daily.
Sponsors
Tianjin Anding Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* a diagnosis of SCZ according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); * receiving stable doses of antipsychotic medication for at least 1 month before enrollment; * age between 18 and 65 years; * provision of written informed consent by patients and their families.
Exclusion criteria
* a current diagnosis of any other DSM-5 psychiatric disorder; * presence of severe physical illness; * receipt of physical treatments such as repetitive transcranial magnetic stimulation or modified electroconvulsive therapy within one month prior to enrollment; * hemolytic anemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency; * pregnant and lactating women; * any factor that would interfere with the participant's ability to provide informed consent or complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the MCCB Overall Composite Score | changes within 0, 12weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in scores on the remaining MCCB domains | changes within 0, 12weeks | 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. |
| Psychiatric Symptoms | changes within 0, 4, 8,12weeks | The psychiatric symptoms of schizophrenia were assessed in all enrolled patients using the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30-item clinician-rated scale yielding a total score ranging from 30 (least symptomatic) to 210 (symptomatic), where higher scores indicate more severe psychopathology. |
| Depressive Symptoms | changes within 0, 4, 8,12weeks | The Hamilton Depression Scale-24 (HAMD-24) was used to assess the severity of depressive symptoms. Each item was scored on a scale of 0 (none) to 4 (severe); the total score ranged from 0 to 76, with higher scores indicating more severe depressive symptoms. |
| Anxiety Symptoms | changes within 0, 4, 8, 12weeks | The Hamilton Anxiety Scale (HAMA) is used to assess the severity of anxiety symptoms. Each item is scored on a scale of 0 (none) to 4 (very severe), with a total score range of 0-56. Higher scores indicate more severe anxiety symptoms. |
| Changes of Fecal Macrogene Sequencing(FMS) | changes within 0, 12weeks | 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 in plasma levels of short-chain fatty acids. | changes within 0, 12weeks | Week 12 changes in plasma short-chain fatty acid levels from baseline. |
| Changes in plasma bile acid levels | changes within 0, 12weeks | Week 12 changes in plasma bile acid from baseline. |
| Changes in plasma tryptophan levels | changes within 0, 12weeks | Week 12 changes in plasma tryptophan from baseline. |
| Changes of CRP | changes within 0, 4, 8, 12weeks | 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 in glycolipid levels | Baseline, week 4, week 8 and week 12 | Glucose and lipid levels were measured at Weeks 0, 4, 8, and 12. |
| Weight changes | Baseline, week4, week8, week12 | Weight was measured at Weeks 0, 4, 8, and 12. |
Countries
China
Outcome results
None listed