Psychobiotics Ameliorate Anxiety and Depression Status in Patients Under Chemotherapy for Gastrointestinal Malignancies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 2
- 主要终点
- Depression changes
研究概览
简要总结
Anxiety and depressive disorders are quite prevalent in the general population. In 2015, it was estimated that 3.6% of the world population (around 264 million individuals) live with depression and 4.4% (around 322 million) with anxiety, while in the recent years of the COVID-19 pandemic, the prevalence of these disorders has significantly increased.
According to the American Psychiatric Association, in 2013 depression was defined as a serious mental illness characterized by decreased mood lasting more than 15 days, a lack of interest, and (even) apathy to normal daily activities. Depression, particularly in its severe form - the major depressive disorder (MDD), is the second leading cause of disability and the most common emotional disorder.
Recent research data indicate that this psychiatric disorder, as also similar neuropsychological conditions (Parkinson's, autism, etc.) have, as their main substrate, a disturbance in the diversity of the gut microbiome. More specifically, it has been shown that there is a direct and bidirectional communication between gut and brain - the "gut-brain-axis". The gut, through its microbiome, communicates with the brain by means of neural, immunological, and metabolic pathways, either directly, through the vagus nerve or indirectly, either through the microbiome immunomodulation or the tryptophan pathway, or by the production of various neuroactive molecules.
The disturbance in the diversity of the gut microbiome, termed dysbiosis, involves changes in the composition and the number of bacteria genera; and is causatively related to depression via the gut-brain axis. The transmission of nerve impulses, both via the hypothalamic-pituitary-adrenal axis and via the vagus nerve is disrupted by dysbiosis, leading to anxiety and depression, or, conversely, stressful conditions, more particularly emotional stress, which triggers an imbalance in the hypothalamic-pituitary-adrenal axis, leading to systemic immune responses and intestinal dysbiosis. This imbalance can clinically manifest with alterations in digestive tract function, knowledge accepted since the beginning of the previous century.
Nowadays, there is considerable evidence that the gut microbiome represents a novel anti-depressant and the term "psychobiotics" has been used to describe those species of probiotic bacteria excreting mental health benefits.
Certain Bifidobacterium and Lactobacillus species have already demonstrated, both experimentally and in clinical studies, their capability to improve mood, reduce anxiety, and enhance cognitive function. On these grounds, it is reasonable to raise the hypothesis that, by restoring the diversity of the gut microbiome, and thus enhancing the population of these specific probiotic species - termed 'psychobiotics', due to their specified functions, - could at least lead to an improvement in neuro-psychological disorders through gut-brain-axis remodeling.
详细描述
Based on the assumption that 1. at least one third of digestive cancer patients operated on - and probably more, when surgery is followed by chemotherapy sessions - suffer from anxiety and depression, 2. psychobiotics can beneficially modify the gut microbiome, 3. psychobiotics can improve the mental health of patients suffering from depression, and 4. there is no other study on the use of psychobiotics in anxiety and/or depression symptoms in patients operated on for digestive tract malignancies and subjected to chemotherapy thereafter the present study was designed to investigate the ability of a probiotic formulation containing bacteria with known psychobiotic properties to change the depression and anxiety status of digestive cancer patients undergoing chemotherapy postoperatively.
This study will be a prospective, double-blind, randomized study against placebo in patients operated on for digestive cancer and undergoing chemotherapy. The study will be conducted in the 1st Surgical Department of the Aristotle University of Thessaloniki, at the AHEPA University Hospital of Thessaloniki, Greece, in collaboration with the Outpatient Surgical Oncology Unit. Permission has already been obtained from the Scientific Council of the AHEPA Hospital (Approval Number: 313/4.7.2023).
The oncologist involved in the study protocol will be responsible for randomization. She will inform the patients who meet the study entry criteria of the purpose of the study, and receiving their written consent after detailed information. Patients having signed the informed consent will then be assigned at random [in a 1:1 ratio] to receive placebo or probiotic regime treatment, according to a computer-based table [randomized.com]. The randomization will be blinded to the study statistician, as well as to the physicians in contact with patients for interviews to facilitate the collection of answers to the questionnaires. Sealed envelops will be used to ensure blinding. Only the study coordinator will be aware of the content, having no further involvement with the patients. Each patient, having signed the consent, will then receive a unique code-number, being a combination of the anatomical location of the tumor, the patient's serial number, a capital letter A or B - blindly indicating the treatment groups - and a small letter, [a,b,c] indicating the physician who contacts each patient.
After patient aggrees to be included in the study, the demographic data that will be obtained in relation to each patient are: gender; age; body weight (in kilograms) and height (in meters) to calculate BMI; reported weight loss in kilograms since the disease diagnosis; marital status; smoking habits (no smoking or number of cigarettes/day); alcohol consumption (type and volume); and the possible use of tranquilizers [mg of active substance]. Optionally, patients will give information as to their educational level (1st, 2nd, or 3rd grade), annual income (<10.000€, 10.001-30.000€, >30.001€/year); and health care insurance (public, private, both). From their medical records cancer type and anatomical localization; cancer stage (TNM classification); type of surgical intervention; and co-morbidity indices (Charlson Comorbidity Index) will be obtained. Additional information will be collated relating to the time lapse since diagnosis (in days); the time lapse from hospital discharge to starting chemotherapy (in days); and the time from starting chemotherapy to study entry (in days).
The probiotic regime under testing is a combination of 4 psychobiotics: Lactobacillus rhamnosus, Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, and Bifidobacterium longum, at a dose of 1.000.000.000/CFU. These for psychobiotics are the main ingredients of the commercially available formula LactoLevure®, ProbioMood [UniPharma, Athens, Greece], which also contains saffron and magnesium. This formula is marketed for "people with an anxious lifestyle who often suffer from symptoms such as low mood or fatigue as a result of stress".
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 and <85
- •Histologically confirmed diagnosis of digestive tract malignancy, the tumor having been surgically resected and the patient currently undergoing chemotherapy sessions
- •Informed consent obtained to participate in the study
排除标准
- •Not understanding the Greek language
- •Pre-existing psychiatric disorders
- •Already receiving probiotic supplements (apart from yoghurt)
- •Participation in another clinical trial
- •Consumption of less than the 90% of treatment sachets/doses (verified by the sachets returned)
- •Those having received during hospitalization other probiotic formulations
结局指标
主要结局
Depression changes
时间窗: at one and 3 months
To evaluate the ability of psychobiotics to change patients' depression status at one and 3 months \[if available\] after patients' recruitment in the study, against placebo treatment. The evaluation of patients' depression status will be performed with the help of Beck Depression Inventory Questionnaire (BDI) and Hamilton Depression Rating Scale (HAM-D). The total score of these questionnaires defines depression severity. BDI total score ranges from 0 to 63 and HAM-D total score ranges from 0 to 50. Regarding BDI a total score \<10 reflects "mild" depression, 10-18 "mild to moderate", 19-29 "moderate to severe", and 30-63 "severe" depression and regarding HAM-D a total of score 0-7: reflects normal condition, 8-18: moderate depression, 19-22: severe depression, and 23-50: very severe depression. The total mean score differences will be compared between the probiotic and the placebo group for both questionnaires.
次要结局
- Anxiety changes 2(at one and 3 months)
- Pain fellness changes(at one and 3 months)
- Anxiety changes 1(at one and 3 months)
- Health related quality of life changes(at one and 3 months)
- Physical weakness changes(at one and 3 months)
- Emotion Regulation changes(at one and 3 months)