Gut Microbiome and Metabolic Dysfunction in Antipsychotic Naïve Patients
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Change in Gut microbiome and DNA
研究概览
简要总结
Antipsychotic (AP) medications are currently the cornerstone of treatment for schizophrenia (SCZ), with off-label prescription rapidly increasing in youth, with an established two-fold increase in standardized mortality ratio attributable to cardiovascular disease in this population. However, APs have been associated with common and serious metabolic adverse effects including weight gain and diabetes, to which youth are disproportionally vulnerable. The Gut Microbiome (GMB) has been suggested as a potential target warranting further study as a mechanism of AP induced weight gain and has also been linked directly with cognition and behavior. It is hypothesized that there will be changes in the gut microbiome overtime with treatment correlated with metabolic measures and that APs will produce changes in glucose tolerance, insulin sensitivity, adipokines, glucagon like peptide (GLP)-1, lipids, fasting glucose, body weight, and cognition.
详细描述
The objectives of the study are to examine the gut microbiome composition and diversity in patients with schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder at 6 weeks and 3 months post antipsychotic initiation. Furthermore, the team aims to investigate causality of antipsychotic (AP)-induced changes in the GMB in relation to metabolic changes. This will be accomplished by transplanting human gut microbiota from patients initiating an AP treatment into germ-free mice (independent animal protocol). The final objective is to observe changes in cognition associated with changes in metabolic factors and gut microbiome.
The hypotheses of the study are twofold: the primary hypothesis is that there will be changes in the gut microbiome overtime with treatment correlated with metabolic measures (i.e. weight, insulin sensitivity, glucose tolerance, lipids) due to treatment in antipsychotic naïve patients, and the gut microbiome of treated patients transplanted into germ-free mice will induce similar metabolic proving causality (separate animal protocol). The secondary hypothesis is that APs will produce changes psychopathology and cognitive outcome measures which will correlate with changes in gutmicrobiome.
Participants will include individuals who are either antipsychotic naïve or have not taken antipsychotics for at least 3 months prior to study participation. Participants will be between 12 and 35 years of age with a diagnosis of schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder, as per DSM-V criteria. Participants will be enrolled to reach n=25 complete data sets. Participants who drop out or who are withdrawn will be replaced.
Following provision of written informed consent, participants will be assessed for suitability for inclusion in the study based on the inclusion and exclusion criteria. Participants will be seen across 5 timepoints, including a screening and baseline visit, as well as 3 follow-up appointments.
Within-group analyses will be conducted to evaluate changes in participants at different time points on measures including anthropometric measures, clinical scales, and fasting bloodwork results. Microbiome analysis will include α-diversity metrics for each sample and β-diversity measures (weighted and unweighted unifrac, Specifically we will analyze changes in the microbiome pre- and post- antipsychotic treatment and whether changes in the microbiome associate with other clinical and biochemical measures. We will also determine whether patients that develop metabolic side effects with antipsychotic treatment have different microbial profiles than those who do not develop these side effects.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 12-35
- •Antipsychotic naïve or antipsychotic treatment for equal to or less than 2 weeks within the past 3 months; the minimum AP dose will be left to the discretion of the PI
- •DSM-5 diagnosis (using SCID-IV-TR with supplemental questions from SCID-5 or SCID-5) of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, and brief psychotic disorder, psychotic disorder NOS. and/or antipsychotic treatment for schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder.
排除标准
- •Previous antipsychotic treatment (greater than two weeks within the preceding 3 months)
- •Presence of DSM-5 diagnosis which is not schizophrenia, schizoaffective disorder, or other specified schizophrenia spectrum and other psychotic disorder
- •Use of any other medications for treatment of lipids, glucose, or weight as deemed to be clinically significant by the PI
- •Use of other medications where the dose has changed within the past 6 weeks which are deemed by the PI to be clinically significant
- •Pregnancy
- •Eating disorder - active or previous
- •Major medical or surgical event within the preceding 3 months
- •Acute suicidal risk
- •Irritable bowel disease, Crohn's disease, and/or diverticulitis/diverticulosis
- •Type I diabetes, kidney/liver disease, and/or cancer
- •Organ transplant
- •Moderate to severe alcohol use , use of street drugs, and/or cannabis use (as deemed by PI)
- •Immunosuppressants and/or anti-inflammatory medications
- •Antibiotic/probiotic use within past 4 weeks
- •Any other medical conditions or lifestyle habits deemed by the PI to impact the integrity of the sample/microbiota
结局指标
主要结局
Change in Gut microbiome and DNA
时间窗: 12 weeks (baseline, week 6, week 12)
Patients will collect fecal samples at home using our well-established protocol at baseline, 6 weeks, and 12 weeks. Participants will be provided a kit containing a sterile specimen container and a cooling pad, as well as a stool collection tube for DNA analyses (OMNIgene•GUT, DNA Genotek Ottawa, ON). Patients will be instructed to transfer several grams of the feces into the specimen container and place the sample in the 2 bioharzard bags and then store in the freezer. On the day of their appointment they will transport the sample on the cooling pad (previously placed in the freezer) to their appointment. When the patient delivers the sample to the research staff, it will be immediately placed in a -80ºC freezer prior to being analyzed. These analyses with fecal samples will be conducted at McMaster University at the Farncombe Family Institute.
次要结局
- Free Fatty Acids (FFA)(12 weeks (baseline, week 6, week 12))
- Abnormal Involuntary Movement Scale (AIMS)(12 weeks (baseline, week 12))
- Cortisol(12 weeks (baseline, week 6, week 12))
- Weight(12 weeks)
- Blood pressure(12 weeks)
- Albumin(12 weeks (baseline, week 6, week 12))
- HbA1c(12 weeks (baseline, week 6, week 12))
- Leptin(12 weeks (baseline, week 6, week 12))
- Clinical Global Impression (CGI)(12 weeks (baseline, week 6, week 12))
- Simpson Angus Scale (SAS)(12 weeks (baseline, week 12))
- Investigation of Mental Rotation, Allocentricity-Egocentricity, and Perspective Taking (IMAP)(12 weeks (baseline and week 12))
- Oral glucose tolerance test(12 weeks (baseline and week 12))
- CBC(12 weeks (baseline, week 6, week 12))
- Insulin(12 weeks (baseline, week 6, week 12))
- Brief Psychiatric Rating Scale 18 item (BPRS)(12 weeks (baseline, week 6, week 12))
- The Calgary Depression Scale for Schizophrenia (CDSS)(12 weeks (baseline, week 6, week 12))
- Birchwood Social Functioning Scale (BSFS)(12 weeks (baseline, week 6, week 12))
- Harvard Youth/Adolescent Questionnaire (YAQ)(12 weeks (baseline, week 6, week 12))
- Height(12 weeks)
- Prolactin(12 weeks (baseline, week 6, week 12))
- GGT(12 weeks (baseline, week 6, week 12))
- Heart Rate(12 weeks)
- Waist Circumference(12 weeks)
- BMI(12 weeks)
- Liver enzymes(12 weeks (baseline, week 6, week 12))
- Bilirubin(12 weeks (baseline, week 6, week 12))
- Fasting blood work(12 weeks (baseline, week 6, week 12))
- Thyroid Stimulating Hormone (TSH)(12 weeks (baseline, week 6, week 12))
- C-peptide(12 weeks (baseline, week 6, week 12))
- DNA(Baseline measure)
- The Positive and Negative Symptom Questionnaire (SANS)(12 weeks (baseline, week 6, week 12))
- Visual Analog Scale (VAS)(12 weeks (baseline, week 6, week 12))
- Quality of Life Scale (QLS)(12 weeks (baseline, week 6, week 12))
- UKU Side Effects Scale(12 weeks (all time points))
- Food Cravings Questionnaire (FCQ)(12 weeks (baseline, week 6, week 12))
- Barnes Akathisia Scale (BAS)(12 weeks (baseline, week 12))
- International Physical Activity Questionnaire (IPAQ)(12 weeks (baseline and week 12))
- MATRICS Consensus Cognitive Battery(12 weeks (baseline and week 12))
研究者
Margaret Hahn
Clinician/Scientist
Centre for Addiction and Mental Health