Fecal Microbiota Transplantation for Parkinson’s Disease: a pilot study

The available literature suggests a role for the gut microbiota in the pathophysiology of Parkinson’s disease (PD). Changing the gut microbiota by means of fecal microbiota transplantation (FMT) could act on the pathophysiology of the disease and development of Levodopa-mediated motor complications in PD patients. In the proposed pilot study, FMT with feces from healthy donors will be performed for the first time in a study in PD patients. We hypothesize that FMT is feasible and safe in this patient group. In addition, we hypothesize that FMT will lead to a decrease of motor complications and PD symptoms in the short term, and an alteration of the intestinal microbiota composition towards that of the donor.

Primary objectives:

1. Assess the feasibility of FMT in PD patients.

2. Assess the safety of FMT in PD patients.

Secondary objectives:

1. Explore whether FMT leads to alterations in motor complications (fluctuations or dyskinesias) and PD symptoms in the long term (up to 12 months post-FMT).

2. Determine alterations in gut microbiota composition and donor-recipient similarity, and their association with PD symptoms and motor complications.

3. Assess the ease of the study protocol.

4. Assess which FMT-related AEs are observed in PD patients after FMT

Single center prospective self-controlled interventional donor-FMT pilot study.

Fecal Microbiota Transplantation

The participants will receive bowel lavage and antibiotics prior to FMT. They are not allowed to eat on the day of FMT prior to FMT.

The FMT-procedure requires a gastroscopy to inject the fecal suspension directly into the horizontal duodenum or to insert a nasoduodenal tube with a pediatric gastroscope for later infusion of the fecal suspension, which are both minimally invasive procedures. The patient and the investigator or gastroenterologist can decide together which route is preferred. The nasoduodenal tube will remain in place until approximately 30 minutes after FMT. On the day of FMT, the patient will be in the hospital for approximately 2-4 hours. During this study, the patient has to visit the LUMC six times in total and will have two telephone appointments. Blood will be drawn three times. Physical examination, questionnaires, diary and collection of stool samples are repeated at each visit after screening (except for the FMT-visit).

FMT is a relatively safe procedure, but patients often experience mild self-limiting adverse events (AEs). The percentage of patients experiencing FMT-attributable AEs is 20-45%. In 0-5% of the patients, FMT-attributable SAEs are reported. The type and probability of specific procedure-related problems and (S)AEs in the group of PD patients is unknown. FMT in this pilot study will be performed via the upper Gl route. Swallowing problems, delayed gastric emptying or decreased Gl motility may increase the risk of aspiration.

Flowever, we will exclude patients that cannot swallow 2 liters of laxatives. Importantly, nasoduodenal tube placement and nasoduodenal feeding are usually carried out without problems in PD patients.

The gut microbiota is considered to have a role in the pathophysiology of PD and in the metabolization of anti-PD medication. Based on animal studies, it is hypothesized that FMT with feces from healthy donors might improve the symptoms of PD, improve the effect of medication such as levodopa and limit their side effects, and/or slow down the disease progression. No studies have been performed with FMT in PD patients so far to confirm these findings. This study will provide crucial Information about the safety and feasibility of this treatment in patients with PD, which, in the near future, could be further explored in larger trials aiming at determining the efficacy of FMT in PD patients. The participating patients will have the chance to experience this novel treatment and may possibly benefit from it.