Impact of Wild Blueberries (Vaccinium Myrtillus) on the Intestinal Barrier, Microbiome and Inflammation in Chronic Colitis - a Prospective Randomized Crossover Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Improvement of the intestinal inflammation status evaluated via fecal calprotectin levels
研究概览
简要总结
The goal of this exploratory, prospective, monocentric randomized crossover study is to investigate the influence of a blueberry-rich diet compared to a blueberry-poor diet on the microbiome, the intestinal barrier and the inflammatory process in IBD patients with chronic colitis.
The main question the study aims to answer is:
- Does a diet rich in blueberries compared to a diet low in blueberries have an influence on disease activity, intestinal inflammation and symptoms in IBD patients with chronic colitis?
Ulcerative Colitis (UC) and Crohn's disease (MC) patients are recruited during an inpatient stay at the Clinic for Internal and Integrative Medicine in Bamberg, Germany. During their routine inpatient stay, patients are treated by an interdisciplinary team using a comprehensive multimodal integrative inpatient therapy concept that combines conventional medicine with a wide range of integrative non-pharmacological treatments, phytotherapy, lifestyle-modification and nutritional therapy. During this time, it is verified whether the patients can participate in the study.
The study consists of two study arms, which are conducted in a cross-over design:
- Intervention arm: in this study arm, participants receive 12 weeks of blueberry therapy in addition to the regular two weeks of inpatient care at the Clinic for Internal and Integrative Medicine in Bamberg. The blueberry therapy includes drinking around 35 g of blueberry powder stirred into water once a day for 12 weeks.
- Control arm: in this study arm, participants receive the standard therapy (integrative medical therapy concept described above) during the regular two-week hospital stay. There is no additional blueberry intake.
Due to the crossover study design, all participants undergo both study arms. This means that each participant takes the supplementary blueberry powder (intervention) for a period of 3 months and the control therapy for 3 months. The order in which the participants receive the forms of therapy is determined randomly. Thus, half of the study participants start the supplementary blueberry intake directly after the inpatient stay, the second half three months later (cross-over principle).
UC and MC patients will:
- initially receive a clinically indicated colonoscopy with confocal laser endomicroscopy (CLE) during their routine inpatient stay at the Clinic for Internal and Integrative Medicine in Bamberg
- return to the clinic for an optional sigmoidoscopy with CLE after 12 and 24 weeks
- answer questionnaires at study start as well as after 12 and 24 weeks to analyze their quality of life, the severity of their symptoms and their disease activity
- give samples of blood, urine, stool and bile fluid as well as intestinal biopsies during the colonoscopy/sigmoidoscopy at study start as well as after 12 and 24 weeks
- document their intake of blueberry powder as well as their symptoms and stool frequencies in a diary throughout the study participation
详细描述
Background:
Chronic inflammatory bowel disease (IBD) affects the lives of millions of people worldwide due to recurrent, severe clinical symptoms, potential complications and ongoing medical interventions. The scientific community currently assumes a multicausal pathogenesis in IBD caused by an unfavorable constellation of genetic predisposition, imbalance of pathogenic to symbiotic gut bacteria (dysbiosis) and harmful environmental and lifestyle factors resulting in an excessive immune response.
The intestinal barrier and the microbiome play a key role in maintaining intestinal balance and health. The intestinal barrier protects our body from bacteria, viruses and fungi in the intestinal lumen, while it enables the absorption of nutrients at the same time. In case of a leaky gut, microbial pathogens or their components can enter the deeper cell layers of the intestine and cause acute and long-term inflammatory reactions. The composition of the gut microbiome, i.e. the community of billions of microorganisms living in the gut, has a significant influence on the intestinal barrier and gut health. Beneficial bacteria stabilize the intestinal barrier, strengthen local defenses (mucin and IgA production) and inhibit pro-inflammatory immune reactions and cell death. In contrast, harmful bacteria (pathobionts) disrupt the intestinal barrier, dysregulate cell death and proliferation, which leads to the release of pro-inflammatory signaling substancesand and an immune response causing inflammation.
While previous attempts to develop pharmacological therapies to improve gut barrier function have been unsuccessful, an increasing number of preclinical and clinical trial results highlight the significant impact of a plant-based diet through its modulatory effect on the gut microbiome and the gut barrier in IBD. However, further research is needed to evaluate the role of individual dietary components and complex dietary interventions with anti-inflammatory potential in the prevention and treatment of IBD.
The high levels of prebiotic food components in a plant-rich diet are of particular importance in the treatment of intestinal barrier disorders and the microbiome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age > 18 years
- •diagnosis of Crohn's Disease (CD) or Ulcerative Colitis (UC) with mild to moderate colitis for at least 6 months (CD: Harvey-Bradshaw-Index Score 5-16; UC: Partial Mayo Score 2-6)
- •stable IBD-specific medication dosage for at least 3 months [such as 5-aminosalicylates (5-ASA), thiopurines or biologicals (therapeutic antibodies such as infliximab, adalimumab, vedolizumab, etc.)]
- •inpatient admission to the Department for Internal and Integrative Medicine at the Sozialstiftung Bamberg, Germany for regular treatment
- •clinical indication and performance of an initial colonoscopy with confocal laser endomicroscopy (CLE)
- •signed informed consent form
排除标准
- •IBD without inflammation of the colon (e.g. Crohn's Disease without colitis)
- •active flare of IBD
- •CRP ≥ 100 mg/l
- •artificial bowel outlet in front of the colon (ileostomy)
- •high regular consumption of blueberries (≥ 300 g cultivated blueberries or ≥ 150 g wild blueberries per week) or administration of blueberry therapy in the last 3 months
- •participation in another therapeutic study within the last 30 days
- •Known intolerance to blueberries or their ingredients such as contained anthocyanins or fructose (e.g. fructose malabsorption)
- •presence of known serious infectious diseases e.g. of the liver such as HIV, hepatitis B and C infection
研究组 & 干预措施
Control group
No wild blueberry
干预措施: Control diet (Other)
Intervention group
wild blueberry
干预措施: blueberry-rich diet (Dietary Supplement)
结局指标
主要结局
Improvement of the intestinal inflammation status evaluated via fecal calprotectin levels
时间窗: week 0, 12, 24
The inflammation status is evaluated through measurement of fecal calprotectin levels in stool samples. This biomarker provides information about the inflammatory status in the intestine and serves as an objective measure of disease activity.
次要结局
- Improvement of Crohn's disease severity evaluated by Harvey-Bradshaw-Index (HBI)(week 0, 12, 24)
- Improvement of ulcerative colitis disease severity evaluated by MAYO-Score(week 0, 12, 24)
- Evaluation of IBD-SI (Inflammatory Bowel Disease Symptom Inventory)(week 0, 12, 24)
- Evaluation of disease-specific quality of life by IBD-Q (Inflammatory Bowel Disease Questionnaire)(week 0, 12, 24)
- Assessment of health-related quality of life with the Short Form 12 Health Survey (SF-12)(week 0, 12, 24)
- Assessment of the severity of the fatigue syndrome with the Multidimensional Fatigue Inventory (MFI-20)(week 0, 12, 24)
- Assessment of perceived stress using the Perceived Stress Scale (PSS-10)(week 0, 12, 24)
- Assessment of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS)(week 0, 12, 24)
- Assessment of food-related quality of life using the FR-QoL-29 questionnaire(week 0, 12, 24)
- Assessment of frequency of consumption and usual portion sizes of particular food groups using the DEGS-Food Frequency Questionnaire(week 0, 4, 8, 12, 16, 20, 24)
- Patient Diary(week 0 to week 24)
- Colonoscopy/Sigmoidoscopy with confocal laser endomicroscopy (CLE)(week 0, 12, 24)
- Histopathological analysis of ileo-colorectal biopsies(week 0, 12, 24)
- Immunohistochemical analysis of ileo-colorectal biopsies(week 0, 12, 24)
- Gene expression analysis of ileo-colorectal biopsies(week 0, 12, 24)
- Evaluation of the systemic inflammatory status by analysis of serum-cytokine concentrations(week 0, 12, 24)
- Complete blood count(week 0, 12, 24)
- C-reactive protein (CRP) in the blood(week 0, 12, 24)
- Erythrocyte Sedimentation Rate (ESR)(week 0, 12, 24)
- Analysis of inflammatory markers in the stool(week 0, 12, 24)
- Analysis of fecal biomarkers to evaluate the integrity of the intestinal barrier(week 0, 12, 24)
- Determination of the I-FABP concentration in the serum(week 0, 12, 24)
- Determination of the fecal β-Defensin concentration(week 0, 12, 24)
- Fecal microbiome analysis(week 0, 12, 24)
- Analysis of fecal metabolites(week 0, 12 and 24)
- Metabolite profiling in the urine(week 0, 12 and 24)
- Analysis of oxidative stress in the urine(week 0, 12, 24)
- Analysis of the antioxidant capacity in the serum(week 0, 12, 24)
- Analysis of the thiol status in the serum(week 0, 12, 24)
- Analysis of the peroxidation of lipids in the serum(week 0, 12, 24)
- Analysis of the composition of bile fluid(week 0, 12, 24)
- Anamnesis(week 0, 12, 24)
- Concomitant medication(week 0, 12, 24)
- Medical history(week 0, 12, 24)
- Social demographics(week 0)
研究者
Jost Langhorst
Univ. Prof. Dr. med
Universität Duisburg-Essen