A 12-weeks Study to Evaluate the Dietary Fiber and Probiotics Treatment in Prevention and Intervention of Weight-gain and Cognitive Impairment of Schizophrenia or Bipolar Disorder

Study Overview
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Brief Summary
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In this study, the investigators will evaluate the efficacy, safety and related mechanism of dietary fiber and probiotics alone and in combination as a add-on treatment in improving the antipsychotic induced weight gain, the cognitive impairment, and psychotic syndrome in schizophrenia or bipolar disorder patients. The study will recruit 100 schizophrenia or bipolar disorder patients who meet the criteria of DSM-5, and then randomized to 4 groups: probiotics group(PB group) dietary fiber group(FB group) probiotics plus dietary fiber group(PF group) and control group(CT group) for a 12-weeks clinical trail. The specific aims are to compare probiotics group versus controls on: 1) clinical core symptoms; 2) cognition;3)metabolic related markers.

Detailed Description
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In this study, the investigators will evaluate the efficacy, safety and related mechanism of dietary fiber and probiotics alone and in combination as a add-on treatment in improving the antipsychotic induced weight gain, the cognitive impairment, and psychotic syndrome in schizophrenia or bipolar disorder patients. The study will recruit 100 schizophrenia or bipolar disorder patients who meet the criteria of DSM-5, and then randomized to 4 groups: probiotics group(PB group) dietary fiber group(FB group) probiotics plus dietary fiber group(PF group) and control group(CT group) for a 12-weeks clinical trail (20 patients per arm) for a 12-weeks clinical trail. Clinical efficacy and safety assessment will be done at screen/baseline, 4 week, 8 week and 12 week. The specific aims are to compare probiotics group versus controls on: 1) clinical core symptoms; 2) cognition; 3) metabolic related markers. Biological samples also will be collected, and stored to research related mechanisms. Clinical symptoms will be measured by the Positive and Negative Syndrome Scale,. Cognitive function will be assessed by the MATRICS Consensus Cognitive Battery. The investigators hypothesize that: 1) dietary fiber and probiotics may improve cognitive impairment of patients with schizophrenia; 2) dietary fiber and probiotics could prevent the cognitive decline of patients with schizophrenia; 3)dietary fiber and probiotics may prevent the antipsychotics induced weight gain in patients with schizophrenia.4)dietary fiber and probiotics may alter oxidative stress indexes or inflammatory biomarkers thus influence the oxidative and inflammatory mechanism.

Official Title
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A 12-weeks Study to Evaluate the Dietary Fiber and Probiotics Treatment in Prevention and Intervention of Weight-gain and Cognitive Impairment of Schizophrenia or Bipolar Disorder

Conditions
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Schizophrenia, Bipolar Disorder

Intervention / Treatment
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* Drug: Bifico (Live combined bifidobacterium,Lactobacillus and Enterococcus capsules, Oral)
* Dietary Supplement: Dietary fiber


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the Diagnostic and Statistical Manual (DSM-V) diagnostic criteria for schizophrenia or bipolar disorder; Patients with a weight gain of more than 10% after taking antipsychotic medications; Male and female with aged 18 to 65 years; PANSS total score < 60 or HAMD-17 total score≤ 7 and YMRS total score<5; Signed the study consent for participation; Not allergy to probiotics or dietary fiber medicine On stable medication and dosage for at least 3 months. Exclusion Criteria: Having history of substance dependence or abuse or whose symptoms are caused by the other diagnosable mental disorders; Having history of traumatic brain injury, seizures or other known neurological or organic diseases of the central nervous system; Taking antidepressants, stimulants, mood stabilizer or accepts electricity shock treatment; Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be manage in an inpatient setting; The routine blood tests showing abnormal renal, liver function; Pregnant or lactating women. No administration of any antibiotics in two mouths

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics Group<br>Probiotics add-on treatment :（live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules, Oral）, each capsule contain more then 1.0*10^7 CFU. Bifico: 840mg Bid. | Drug: Bifico (Live combined bifidobacterium,Lactobacillus and Enterococcus capsules, Oral)<br>* Bifico 840mg Bid<br>|
| No Intervention: Control Group<br>No probiotics or dietary fiber group. | |
| Experimental: Dietary fiber Group<br>Prebiotics add-on treatment: dietary fibers compound powder, 30g bid | Dietary Supplement: Dietary fiber<br>* dietary fiber compound powder 30g bid<br>|
| Experimental: Dietary fiber Probiotics group<br>Dietary fiber and probiotics group: receiving both Bifico 840mg Bid and dietary fiber 30g bid. | Drug: Bifico (Live combined bifidobacterium,Lactobacillus and Enterococcus capsules, Oral)<br>* Bifico 840mg Bid<br>Dietary Supplement: Dietary fiber<br>* dietary fiber compound powder 30g bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MATRICS Consensus Cognitive Battery (MCCB) composite score | The investigators will use the MATRICS Consensus Cognitive Battery (MCCB) Composite score as primary cognitive outcome measure before and after treatment at different follow up point. | 12 weeks | 
| Body Mass Index | The body mass index (BMI) or Quetelet index is a value derived from the mass (weight) and height of an individual. The BMI is defined as the body mass divided by the square of the body height, and is universally expressed in units of kg/m2, resulting from mass in kilograms and height in metres. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive And Negative Syndrome Scale (PANSS) | The change of Positive And Negative Syndrome Scale (PANSS) total, positive and negative symptoms before and after treatment at different follow up point. | 12 weeks | 
| Lipid metabolism related blood index | Other lipid metabolism related marker such as LDL,HDL,TG, CHO (all in mmol/L) | 12 weeks | 
| Physical exam index | Body weight related physical exam index: waist circumference,hip line (cm) | 12 weeks | 
| Hamilton Depression Scale and Young Manic Rating Scale (YMRS) | The change of total score of the Hamilton Depression Scale and the Young Manic Rating Scale (YMRS), used to measure mania and depression symptoms of bipolar disorder. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, probiotics, cognitive impairment, Metabolic syndrome, clinical trail, Efficacy, Safety, Dietary fiber, Bipolar Disorder