A Double-blind, Placebo-controlled, Randomized Clinical Trial Investigating Fecal Microbiota Transplantation for Parkinson's Disease and Its Effect on Symptoms and Disease Progression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Changes in clinical symptoms as scored on the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale)
研究概览
简要总结
Parkinson's disease (PD) is the second most common neurodegenerative disorder and due to the lack of early diagnosis and effective therapy, represents a large burden for our society and healthcare system. The last years, it became increasingly apparent that non-motor symptoms, including gastrointestinal dysfunction, precede the onset of the typical PD motor symptoms by several years. Moreover, emerging evidence suggests that PD, and more specifically the aggregation of alpha-synuclein, starts in the gut before spreading to the brain. Additionally, recent microbiome studies consistently showed microbiota differences between PD patients and healthy controls.
The ultimate goal of this project is to address the impact of gut dysbiosis and the restoration of gut homeostasis by fecal microbiota transplantation (FMT) on the development and progression of PD. We will identify PD-specific changes in microbiota composition and gut inflammation and determine the effect of a 'microbiome-reset' approach through FMT in PD patients on the identified changes and more importantly on disease symptoms and progression.
详细描述
In this study the effects of fecal microbiota transplantation (FMT) on patients with Parkinson's disease will be investigated in a double-blind, placebo-controlled randomized clinical trial.
At time of FMT, forty patients will be randomized in a double-blinded fashion to the treatment arm (healthy donor stool) or placebo arm (own stool). Transplantation will be performed through nasojejunal administration.
Donors for this study will be recruited from a healthy donor pool who will donate stool after clearance of a strict inclusion protocol which will assess the presence of any infectious diseases. Donor stool will be frozen and stored until day of FMT.
Participants will be screened for relevant inclusion and exclusion criteria and will have to sign an informed consent before admission to the study.
Prior and on a regular basis following the FMT participants will be evaluated through neurological clinical examination and standardized clinical scoring scales including MDS-UPDRS, PDQ-39, NMSS and MoCA. Stool samples will be taken regularly and stored at -80°C for microbiome analysis. Blood will be collected for determining relevant markers. All participants will also undergo sampling for oral and nasal microbiome. Follow-up will continue for a total duration of one year.
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
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for patients:
- •Signed informed consent.
- •Clinical PD diagnosis (MDS criteria)
- •Hoehn & Yahr score of 2-3 in OFF
- •Age of motor symptoms onset > 50 years
排除标准
- •for patients:
- •First degree relative or more than one relative with PD
- •Diagnosis of dementia or MMSE < 25
- •Diagnosis of major depression or psychosis (DSM-V criteria)
- •Any of the following within the previous 2 months: hospital admission, narcosis or sedation, abdominal trauma
- •Primary disease of gastrointestinal tract (exception: chronic gastritis)
- •Previous abdominal or anorectal surgery (causing structural abnormalities of the intestines)
- •Any of the following within the previous 2 months: gastrointestinal or respiratory tract infection, food intoxication
- •The use of probiotics or antibiotics within three months prior to FMT
- •Contra-indications for colonoscopy
- •Other immune disorder or clinical immunosuppression
- •Drug abuse
- •Malignancy
- •Any severe comorbidity that might interfere with the study course as determined by the treating physician
- •Pregnancy or inadequate anti conception for the duration of the trial
- •Inclusion criteria for donors
- •age 18 - 75 years
- •signed informed consent
- •normal screening protocol, including screening for infectious diseases, according to the recommendations of the Superior Health Council of Belgium concerning the safety and quality of fecal transplantation in humans
- •Exclusion criteria for donors
- •presence of gastrointestinal symptoms
- •gastro-intestinal or other important comorbidity
- •obesity or metabolic syndrome
- •history of malignancy both gastrointestinal or systemic
- •presence of known colon polyps
- •recent placing of piercings/tattoos
- •sexual risk behaviour
- •antimicrobial therapy 3 months prior to donation
- •living in the same household as a Parkinson's disease patient
研究组 & 干预措施
Treatment group: Donor FMT
Fecal microbiota transplantation using fecal matter from a healthy donor selected through strict inclusion criteria assessing the presence of any infectious diseases.
干预措施: Donor FMT (Other)
Control group: Autologous FMT
Fecal microbiota transplantation using the patient's own fecal matter.
干预措施: Autologous FMT (Other)
结局指标
主要结局
Changes in clinical symptoms as scored on the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale)
时间窗: 3 months, 6 months, 12 months
The MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) has four parts: Part I (non-motor experiences of daily living; 13 items), Part II (motor experiences of daily living; 13 items), Part III (motor examination; 33 scores based on 18 items, several with right, left or other body distribution scores) and Part IV (motor complications; 6 items). Each item has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Part III will be clinically scored in an OFF-medication state. Subscales are analyzed separately. References: 1. Goetz, C. et al. Movement Disord 22, 41-47 (2007). 2. Goetz, C. et al. Movement Disord 23, 2129-2170 (2008).
次要结局
- Changes in gastrointestinal symptoms as assessed by the Rome IV questionnaire(3 months, 6 months, 12 months)
- Changes in non-motors symptoms as scored on the Non-motor symptoms scale for Parkinson's disease (NMSS)(3 months, 6 months, 12 months)
- Changes in cognition as scored on the Montreal Cognitive Assessment (MoCA)(3 months, 6 months, 12 months)
- Changes in quality of life as scored on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39)(3 months, 6 months, 12 months)
- Number of participants with a change in required anti-PD symptomatic or levodopa therapy(3 months, 6 months, 12 months)