Fecal Microbiota Transplantation for Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Donor FMT; Autologous FMT
Intervention type(s): Other; Other
Intervention description(s): 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.; 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 intervention name(s): FMT with donor stool; FMT with own stool
Allocation: Randomized
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)
Primary purpose: Treatment
Keywords: Parkinson's disease; Fecal microbiota transplantation; Microbiome; Gut-brain axis