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…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoints:
1. Feasibility of FMT in PD patients: the number of included patients that
cannot undergo FMT due to a patient- or procedure-related reason.
2. Safety of FMT in PD patients: FMT-related serious adverse events (SAEs)
Secondary outcome
1. Alterations in gut microbiota structure (16S rRNA gene amplicon sequencing)
after FMT, with comparison to the donor gut microbiota, and how these associate
with PD symptoms and motor complications.
2. Changes after FMT (as compared to the change observed after one-week
standard-of-care observation) and differences between patient groups based on
the selected donors on the following aspects:
• Severity of motor complications, i.e. number and duration of off periods and
periods with troublesome dyskinesias per day (3 days diary)
• MDS-UPDRS (on medication)
• Required PD medication dose
• Hoehn and Yahr score
• Q10 questionnaire (wearing off)
• Montreal Cognitive Assessment (MOCA)
• Severity of GI symptoms and defecation frequency
• Bristol stool scale
• Other non-motor symptoms (SEverity of Non-dopaminergic Symptoms in
Parkinson*s Disease (SENS-PD) scale)
3. Ease of the study protocol, assessed by the reasons for refrainment of
participation in the
study after receiving full information at V1, and study load for participants,
assessed bij 0-10 scale and open questions.
4. FMT-related AEs in PD patients after FMT, assessed by the registration of
FMT-related AEs.
Background summary
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.
Study objective
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
Study design
Single center prospective self-controlled interventional donor-FMT pilot study.
Intervention
FMT, with vancomycin and bowel lavage as pre-treatment and domperidone prior to
FMT.
Study burden and risks
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 GI route. Swallowing problems, delayed gastric
emptying or decreased Gl motility may increase the risk of aspiration. However,
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.
A preliminary version of this study protocol was discussed with two Parkinson
patients (patient-investigators), appointed by the Dutch Parkinson patients
association (Parkinson vereniging), to review the study load, the safety and
the patient-centered value of the study.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
- Clinical diagnosis of idiopathic PD according to UK Brain Bank criteria
- PD disease duration of at least five years.
- Use of levodopa.
- Presence of motor complications (motor fluctuations or dyskinesias), despite
adequate PD medication and regardless of severity.
- Written informed consent.
Exclusion criteria
- Hoehn and Yahr scale stage 5 (most severe stage in scale for severity of PD
motor symptoms).
- Comorbidity or condition impairing ability to participate in the study
according to the investigators.
- Current use of probiotics or in the previous three months.
- Unstable PD with change in type or dose of PD medication in the previous
three months.
- Symptoms of a GI infection during the previous three months.
- Current need of antibiotics or use in the previous three months.
- Current GI malignancy or in the previous six months.
- Known obstructions, paralysis or severe motility problems of the
gastrointestinal tract, or severe dysphagia with incapability of swallowing 2
liters of macrogol + electrolytes, or inability to receive oral feeding.
- Known diagnosis of Inflammatory Bowel Disease (IBD) or celiac disease.
- Intestinal resection in medical history.
- Recent intraabdominal surgery(< 3 months).
- Platelet count < 70x10^9/L
- Participation in another study within 16 weeks of screening visit.
- Known severe food allergy or allergy to medication that a donor could have
used (intake may lead to a life threatening situation).
- Immunocompromised state.
- Current use of immunosuppressants or opiates, or in the previous month.
- For women with child-bearing potential: Pregnancy; current wish to be
pregnant or absence of contraception; lactation.
- Impaired ability to understand the study content and to give written informed
consent.
- Unwilling or not capable to comply with the study requirements.
- Inability to communicate in Dutch.
- Inability to visit the LUMC.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL73701.058.20 |
| OMON | NL-OMON25789 |