Clinical trial NCT03808389: Fecal Microbiota Transplantation for Parkinson's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Keywords: Parkinson's disease
Fecal microbiota transplantation
Microbiome
Gut-brain axis
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: the Flanders Institute for Biotechnology
name: Research Foundation Flanders
name: Vlaamse Parkinson Liga
name: Parkili
First posted: 2019-01-17
Enrollment: 49
Sex: ALL
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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).
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria 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

Exclusion Criteria 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

Primary outcomes:
measure: Changes in clinical symptoms as scored on the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale)
timeFrame: 3 months, 6 months, 12 months
Secondary outcomes:
measure: Changes in non-motors symptoms as scored on the Non-motor symptoms scale for Parkinson's disease (NMSS)
timeFrame: 3 months, 6 months, 12 months
measure: Changes in quality of life as scored on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39)
timeFrame: 3 months, 6 months, 12 months
measure: Changes in cognition as scored on the Montreal Cognitive Assessment (MoCA)
timeFrame: 3 months, 6 months, 12 months
measure: Number of participants with a change in required anti-PD symptomatic or levodopa therapy
timeFrame: 3 months, 6 months, 12 months
measure: Changes in gastrointestinal symptoms as assessed by the Rome IV questionnaire
timeFrame: 3 months, 6 months, 12 months
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: Ghent University, Ghent University Hospital
name: Patrick Santens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: