Pilot Study of Faecal Microbiota Transplantation in Multiple Sclerosis, a Phase-1 Study

Recent research has implicated dysbiosis (alteration of function and
composition of the microbiota) in the gut microbiota in the pathophysiology of
MS. The dysbiosis found in MS patients seems to correlate with the distinct
immunological findings associated with MS. Restoring dysbiosis could provide a
new therapeutic approach in MS.

Overall the safety to perform FMT has to be assessed before potential trial
powered for efficacy can be performed. In this study we aim to treat 10
patients with different forms of MS to assess if FMT is safe to perform.

Primary Objective: To assess the safety of FMT treatment in MS patients,
measured by number of (serious) adverse events, clinical relapses, disease
progression (EDSS), serum neurofilament levels, and MRI.

Secondary Objective(s): Systemic response to FMT measured by immunological
parameters (e.g. lipidomics); microbiota dynamics assessed by faecal sampling.

Mono-centre, open-label, interventional clinical pilot study, conducted in
Amsterdam UMC, location VU University Medical Center. Estimated start of study
is January 2020. The study is expected to be completed within one year.

All patients will be treated twice with FMT, after pre-treatment with oral
vancomycin and bowel lavage. A single donor will be used for all participants.
Faecal suspension will be provided by de Nederlandse Donor Feces Bank (NDFB)

FMT will be performed via endoscopical placement of a duodenal tube. The first
FMT will be preceded by a 4 day course of 250 mg vancomycin QID, and a
bowellavage.

Participants will undergo FMT twice under mild sedation, with an interval of
two weeks. Outpatient clinic visits are scheduled before FMT, and one week, one
month and six months after FMT. At each visit samples of blood and faeces are
collected, questionnaires are completed and a physical examination is
performed. Cerebral MRI-scans are made before treatment and after six months.
FMT will lead to moderate discomfort during the procedure. FMT is considered to
be safe, provided that adequate screening of donors and faeces is assured, as
it is in this study. There is extensive experience with FMT in patients with
multiple recurrent Clostridium difficile infection. Although these patients are
much more vulnerable than the MS patients that we intend to include in this
study, serious side effects are rare. In studies with less stringent safety
measures serious side effects have been reported. We do not expect a clear
benefit for patients participating in this study