A 12-week, Randomized, Double-blind, and Placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, And Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet
试验速览
- 阶段
- 不适用
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- The changes in Symptom Checklist-90 (SCL-90) total score to measure the severity of psychopathological impairment
研究概览
简要总结
More and more evidence confirms the relationship between the gut-brain-microbiota axis and the symptoms of mood disorders. A potential pathway connecting the intestines and the brain in depression is inflammation. Interventions for reducing inflammation and restoring the integrity of the intestinal mucosa are promising approaches in patients with major depressive disorder (MDD). Gut dysbiosis and the diet containing gluten are potential factors may be factors that negatively affect the communication between intestinal and brain. Gluten has a high immunogenic potential and affinity for the intestinal mucosa layer. In patients with an abnormal reaction to gluten, the elimination diet led to improved mood symptoms. However, the relationship between gluten and depression is still poorly understood. Intestinal microbiota can affect the digestion of gluten and reduce its immunogenic potential. Studies have shown that probiotic supplementation has an anti-inflammatory effect, can lead to changes in intestinal permeability and alleviate the symptoms of depression. This evidence supports the need for co-therapy, including the elimination of gluten and the restoration of intestinal eubiosis to reduce inflammation and modulate the gut-brain-microbiota axis. The objective of the SANGUT study is to determine the impact of interventions concerning the gut-brain-microbiota axis (probiotic supplementation, gluten-free diet and their combination) on the mental state, markers of inflammation and markers of intestinal permeability in adult patients with MDD. The study will last 12 weeks and consist of four visits (V): V0 - Screening (Day 0), V1 - Baseline (up to 1 week after Screening), V2 (six weeks after Baseline), V3 - End of the study (12 weeks after Baseline). The main hypothesis is that probiotic supplementation and/or a gluten-free diet will reduce the symptoms of depression, lower the level of inflammatory markers and favourably affect the integrity of the intestinal mucosal barrier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Outpatients aged 18-60 years old;
- •Signed written Informed Consent Form;
- •Meet the DSM-5 criteria for MDD;
- •Body mass index (BMI) ≥18.5 kg/m2 and ≤30 kg/m2;
- •MADRS (Montgomery-Asberg Depression Scale) total score at screening (V0) and at baseline (V1) of 20 points or more (moderate or severe depression);
- •A willingness and motivation to follow the study protocol.
排除标准
- •Diagnosis of autoimmune, neurological, immunocompromised, thyroid, inflammatory bowel diseases, diabetes, cancers, and/or IgE-dependent allergy;
- •Psychiatric comorbidities (except specific personality disorder) including mental retardation, organic brain dysfunction, or addiction (except nicotine and caffeine);
- •High risk of suicide in the investigator's opinion;
- •An infection one month before the study baseline visit (V1);
- •The use of antibiotics and/or probiotics three months prior to the study;
- •Glucocorticosteroids and/or metformin treatment;
- •Intake of any other drugs which in the investigator' opinion may affect the results of study;
- •Intake of any dietary supplementation (except for vitamin D according to the "Vitamin D supplementation guidelines, 2018") which in the investigator' opinion may affect the results of the study;
- •Changes in a pharmacotherapy and/or psychotherapy of MDD 2 weeks before the trial entry;
- •Electroconvulsive therapy (ECT) 12 months before the trial entry;
- •No specific diet (e.g., elimination, vegan, reduction) and changes in physical activity 4 weeks before the trial entry;
- •Pregnancy or lactation.
结局指标
主要结局
The changes in Symptom Checklist-90 (SCL-90) total score to measure the severity of psychopathological impairment
时间窗: from the date of randomization until the end of the study up to 12 weeks
A 90-item self-reported inventory to evaluate a broad range of psychological problems and symptoms of psychopathology. The SCL-90 measure symptom intensity on nine different subscales: somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism. Each item yields a score of 0 to 4 (overall score ranges from 0 to 364). The higher score indicates more severity of symptoms.
The changes in Montgomery-Åsberg Depression Rating Scale(MADRS) total score to measure the severity of depression symptoms
时间窗: from the date of randomization until the end of the study up to 12 weeks
A 10-item questionnaire to measure the severity of depressive symptoms in individuals with mood disorders. The assessment is performed by an experienced clinical psychiatrist. Each item yields a score of 0 to 6 (overall score ranges from 0 to 60). The higher score indicates a higher severity of the depressive episode. MADRS cut-off points include: * 0 to 6: symptom absent * 7 to 19: mild depression * 20 to 34: moderate depression * more than 34: severe depression
The changes in the 36-Item Short Form Survey (SF-36) total score to measure the quality of life
时间窗: from the date of randomization until the end of the study up to 12 weeks
A 36-item self-reported survey to evaluate a health status including vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Raw scores are transforming to 0-100 scale. The higher score indicates a better health state.
The changes in the Perceived Stress Scale (PSS-10) total score to measure the stress levels
时间窗: from the date of randomization until the end of the study up to 12 weeks
A 10-item self-reported questionnaire to measure the perception of stress. Each item yields a score of 0 to 4 (overall score ranges from 0 to 40). The higher score indicates higher perceived stress.
The changes in Beck Depression Inventory (BDI) total score to measure the severity of depression symptoms
时间窗: from the date of randomization until the end of the study up to 12 weeks
A 21-item multiple-choice self-report inventory to measure the severity of depression. Each item yields a score of 0 to 3 (overall score ranges from 0 to 63). The higher score indicates more severe depression symptoms. BDI cut-off points include: * 0 to 9: no/minimal depression * 10 to 18: mild depression * 19 to 29: moderate depression * 30 to 63: severe depression
次要结局
- Changes in serum levels of high-density lipoprotein (HDL) cholesterol(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of high-specific C-reactive protein (hs-CRP)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of intestinal fatty acid-binding protein (I-FABP/FABP-2)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of lipopolysaccharide biding protein (LBP)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in stool short-chain fatty acids (SCFAs) levels(from the date of randomization until the end of the study up to 12 weeks)
- Changes in Trail Making Test (TMT) to measure the cognitive abilities(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of interleukin 1beta (Il-1beta)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of anti-gliadin (anti-AGA) IgG antibodies(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of low-density lipoprotein (LDL) cholesterol(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of total cholesterol(from the date of randomization until the end of the study up to 12 weeks)
- Changes in diversity in microbial community between samples (beta-diversity)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of insulin(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of cortisol(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of anti-tissue transglutaminase (anti-TG2) IgG antibodies(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of anti-gliadin (anti-AGA) IgA antibodies(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of triglycerides (TG)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of alanine aminotransferase (ALT)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in diversity in microbial community in a single sample (alpha-diversity)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of tumor necrosis factor alpha (TNF-alpha)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of interleukin 6 (Il-6)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of glucose(from the date of randomization until the end of the study up to 12 weeks)
- Changes in serum levels of aspartate aminotransferase (AST)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in electroencephalography (EEG) analysis to assess the functional connectivity (FC)(from the date of randomization until the end of the study up to 12 weeks)
- Changes in Gastrointestinal Symptom Rating Scale (GSRS) total score to measure intensity of experienced gastrointestinal symptoms(from the date of randomization until the end of the study up to 12 weeks)