Fecal Microbiota Transplantation for Parkinson's Disease
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|ClinicalTrials.gov Identifier: NCT03808389|
Recruitment Status : Recruiting
First Posted : January 17, 2019
Last Update Posted : April 24, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Other: Donor FMT Other: Autologous FMT||Not Applicable|
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.
Prior to FMT, all participants will undergo a colonoscopy to exclude contra-indications for FMT and to collect mucosa-adherent microbial samples and gastrointestinal tissue biopts. This colonoscopy will be repeated once, one year following the FMT.
The primary endpoint in this study will be a change in clinical status measured through the MDS-UPDRS. Additionally, motor and non-motor symptoms will be correlated with serum markers of inflammation and gut and central nervous system barrier function, microbiota changes and gastrointestinal biopsy analysis of inflammation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||40 patients with Parkinson's disease (Hoehn & Yahr score 2-3) will be randomly allocated (20 vs. 20) to either fecal microbiota transplantation with donor stool or autologous fecal microbiota transplantation (= own stool).|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Double-blind, Placebo-controlled, Randomized Clinical Trial Investigating Fecal Microbiota Transplantation for Parkinson's Disease and Its Effect on Symptoms and Disease Progression|
|Actual Study Start Date :||January 30, 2019|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Experimental: 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.
Other: Donor FMT
Fecal microbiota transplantation through nasojejunal administration. Fecal matter will be collected prior to the start of the study from healthy donors and will be frozen at -80°C after thorough screening for infectious diseases. At the time of transplantation, samples will be thawed and administrated to the patients in the treatment group.
Other Name: FMT with donor stool
Sham Comparator: Control group: Autologous FMT
Fecal microbiota transplantation using the patient's own fecal matter.
Other: Autologous FMT
Fecal microbiota transplantation through nasojejunal administration. Fecal matter will be collected prior to the start of the study from each patient and will be frozen at -80°C after thorough screening for infectious diseases. At the time of transplantation, samples will be thawed and administrated to the patients in the control group.
Other Name: FMT with own stool
- Changes in clinical symptoms as scored on the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) [ Time Frame: 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.
- Goetz, C. et al. Movement Disord 22, 41-47 (2007).
- Goetz, C. et al. Movement Disord 23, 2129-2170 (2008).
- Changes in non-motors symptoms as scored on the Non-motor symptoms scale for Parkinson's disease (NMSS) [ Time Frame: 3 months, 6 months, 12 months ]
Non-motor symptoms scale for Parkinson's disease (NMSS). Non-motor symptoms are assessed over the last month. Each symptom is scored with respect to:
Severity: 0 = None; 1 = Mild: symptoms present but causes little distress or disturbance to patient; 2 = Moderate: some distress or disturbance to patient; 3 = Severe: major source of distress or disturbance to patient.
Frequency: 1 = Rarely (<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time).
NMSS contains nine dimensions: cardiovascular (2 items), sleep/fatigue (4 items), mood/cognition (6 items), perceptual problems (3 items), attention/memory (3 items), gastrointestinal (3 items), urinary (3 items), sexual function (2 items), and miscellaneous (4 items).
Subscores are calculated through multiplication of frequency x severity. Total score is calculated by adding all subscores, range 0-360.
Reference: Chaudhuri, K. R. et al. Mov. Disord. 22, 1901-11 (2007).
- Changes in quality of life as scored on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39) [ Time Frame: 3 months, 6 months, 12 months ]
Parkinson's Disease Quality of Life Questionnaire. All 39 questions are coded in the same way: 0 = Never; 1 = Occasionally; 2 = Sometimes; 3 = Often; 4 = Always (or cannot do at all, if applicable).
The different dimensions are mobility (10 items), activities of daily living (6 items), emotional well being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items).
Each dimension is calculated as a scale from 0 to 100 (0 = no problem at all; 100 = maximum level of problem). Formula for scoring each dimension = (sum of scores of each question in dimension)/ (4 x number of questions in dimension) x 100.
The Single Index score: PDQ-SI= summing the eight dimensions and then dividing by eight.
Reference: Jenkinson, C., Fitzpatrick, R., Peto, V., Greenhall, R. & Hyman, N. Age Ageing 26, 353-7 (1997).
- Changes in cognition as scored on the Montreal Cognitive Assessment (MoCA) [ Time Frame: 3 months, 6 months, 12 months ]
The Montreal Cognitive Assessment (MoCA) assesses several cognitive domains: short-term memory, visuospatial abilities, executive functions, attention, concentration, working memory, language, orientation to time and place. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal.
Reference: Nasreddine, Z. et al. J Am Geriatr Soc 53, 695-699 (2005).
- Number of participants with a change in required anti-PD symptomatic or levodopa therapy [ Time Frame: 3 months, 6 months, 12 months ]
- Changes in gastrointestinal symptoms as assessed by the Rome IV questionnaire [ Time Frame: 3 months, 6 months, 12 months ]The Rome IV criteria for functional constipation and irritable bowel syndrome are assessed to evaluate potential change in gastrointestinal symptoms following the fecal microbiota transplantation.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03808389
|Contact: Arnout Bruggeman, MD||+32 93 32 53 firstname.lastname@example.org|
|Ghent University Hospital||Recruiting|
|Ghent, Belgium, 9000|
|Principal Investigator:||Patrick Santens, MD, PhD||Ghent University, Ghent University Hospital|