Clinical trial NCT02708316: The Gut Metagenome Research of Schizophrenia
Official title: The Gut Metagenome Research of Schizophrenia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Schizophrenia
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Rehabilitation Hospital of Bao Ji City
name: Center Hospital of Xian Yang City
name: Mental Health Center of Wei Nan City
First posted: 2016-03-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The cases included the first episode or recurrent acute-exacerbation schizophrenia patients who correspond to the DSM-Ⅵ diagnostic criteria. The healthy population is matched with cases based on gender, age, nationality, smoking, diet, education and socioeconomic status.

Brief summary: Research already found that patients with autistic spectrum disorders lack of Prevotella intestinal type, then schizophrenia patients may also show the specific intestinal type, so investigators want to detect the gut metagenome of schizophrenia patients by high-throughput DNA sequencing to find specific intestinal type, so as to achieve the purpose of schizophrenia diagnosis. According to the detection of inflammatory factors in the blood, nerve growth factor in the cerebrospinal fluid, to find the mechanism of the gut-microbes-brain axis. Furthermore, investigators want to identify intestinal strains involved in weight gain and metabolic disorders such as blood glucose and lipids induced by antipsychotic drugs.

Detailed description: A prospective observational study will be conducted and cases will be recruited by multi-center cooperation. Investigators plan to collect 100 schizophrenic patients as case group, 100 healthy people as control group. Investigators will observe schizophrenia patients who use the single drug of risperidone in the treatment and follow up the patients on day 1, the third week, the third month, the sixth month and the first year. In addition, the other two groups of patients with schizophrenia will be included, one with olanzapine and the other with aripiprazole. There are three objectives:

1. Compare healthy population with schizophrenia patients in the difference of gut metagenome and inflammatory factors in the blood, stool samples aimed at detecting the difference of composition of intestinal microorganism;
2. Observe the change of intestinal microorganism, inflammatory factors, γ-aminobutyric acid of schizophrenic patients who received risperidone treatment according to the blood, stool samples, cerebrospinal fluid during the follow-up period.
3. Study the difference of intestinal flora composition between schizophrenia patients with metabolic disorder and schizophrenia patients without metabolic disorder after olanzapine or aripiprazole treatment and discuss the relationship between intestinal flora composition and metabolic disorder.

Eligibility criteria: Inclusion Criteria:

* The first episode or recurrent acute-exacerbation schizophrenia patients who correspond to the Diagnostic and Statistical Manual of Mental Disorders-Ⅵ (DSM-Ⅵ) diagnostic criteria.
* Between 18 and 45 years old (including 18 and 45 years old, male or female).
* Patients never accepted full range of psychotropic drugs before admission(taking psychotropic drug less than 5 days before admission)
* the duration of recurrent patients is less than 5 years
* the period of taking psychiatric drug before admission is no more than 2 weeks.
* didn't use of antibiotics within consecutive 3 days in recent 3 months.
* meet the indications of a single antipsychotic risperidone treatment.
* All the patients must have a good family support and comply with the requirements and signed informed consent
* The PANSS score is greater than 60 or equal to 60.
* BMI is greater than or equal 17.5 and less than or equal to 30.

Exclusion Criteria:

* Patients have severe unstable cardiovascular disease, liver disease, kidney disease, blood disease and endocrine disease or history.
* Patients have the history of systematic disease or history of malignant tumor or relevant complications.
* Patients have the activity of gastrointestinal diseases.
* Patients have organic brain disease or complications and mental retardation.
* According to the DSM-Ⅵ diagnostic criteria , patients have drug abuse or drug dependence and incomplete remission.
* glutamic-oxalacetic transaminase (AST) or glutamic-pyruvic transaminase (ALT) is 2 times higher than the normal limit.
* Renal dysfunction, creatinine is higher than the upper limit of normal value.
* The women in pregnancy or lactation now, and may be in pregnant during the study period.
* Patients are allergic to risperidone.

Primary outcomes:
measure: species-level molecular operational taxonomic units
timeFrame: at the beginning
measure: species-level molecular operational taxonomic units
timeFrame: the third month
Secondary outcomes:
measure: concentration of inflammatory factors
timeFrame: at the beginning
measure: concentration of inflammatory factors
timeFrame: the third week
measure: concentration of inflammatory factors
timeFrame: the third month
measure: concentration of inflammatory factors
timeFrame: the sixth month
measure: concentration of inflammatory factors
timeFrame: one year
measure: concentration of γ-aminobutyric acid
timeFrame: at the beginning
measure: concentration of γ-aminobutyric acid
timeFrame: the sixth month
measure: gene profiles
timeFrame: at the beginning
measure: gene profiles
timeFrame: the third month
measure: metagenomic linkage groups
timeFrame: at the beginning
measure: metagenomic linkage groups
timeFrame: the third month
measure: Encyclopedia of Genes and Genomes (KEGG) ortholog
timeFrame: at the beginning
measure: Encyclopedia of Genes and Genomes (KEGG) ortholog
timeFrame: the third month
measure: module and pathway profiles of faecal microbiota
timeFrame: at the beginning
measure: module and pathway profiles of faecal microbiota
timeFrame: the third month
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Xiancang Ma, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References: