Fecal Microbiota Transplantation for Parkinson's Disease

NCT ID: NCT03808389

Last Updated: 2023-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2022-12-09

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment group: Donor FMT

Fecal microbiota transplantation using fecal matter from a healthy donor selected through strict inclusion criteria assessing the presence of any infectious diseases.

Group Type: EXPERIMENTAL

Donor FMT

Intervention Type: OTHER

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.

Control group: Autologous FMT

Fecal microbiota transplantation using the patient's own fecal matter.

Group Type: SHAM_COMPARATOR

Autologous FMT

Intervention Type: OTHER

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.

Interventions

Donor FMT

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.

Intervention Type: OTHER

Autologous FMT

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.

Intervention Type: OTHER

Other Intervention Names

FMT with donor stool; FMT with own stool

Eligibility Criteria

Inclusion Criteria

• Signed informed consent.
• Clinical PD diagnosis (MDS criteria)
• Hoehn & Yahr score of 2-3 in OFF
• Age of motor symptoms onset > 50 years

• 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

• 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

• 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: collaborator

the Flanders Institute for Biotechnology

UNKNOWN

Sponsor Role: collaborator

Research Foundation Flanders

OTHER

Sponsor Role: collaborator

Vlaamse Parkinson Liga

UNKNOWN

Sponsor Role: collaborator

Parkili

UNKNOWN

Sponsor Role: collaborator

University Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Santens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ghent University, Ghent University Hospital

Locations

Ghent University Hospital

Ghent, , Belgium

Countries

Belgium

References

Bruggeman A, Vandendriessche C, Hamerlinck H, De Looze D, Tate DJ, Vuylsteke M, De Commer L, Devolder L, Raes J, Verhasselt B, Laukens D, Vandenbroucke RE, Santens P. Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial. EClinicalMedicine. 2024 Mar 27;71:102563. doi: 10.1016/j.eclinm.2024.102563. eCollection 2024 May.

Reference Type: DERIVED

PMID: 38686220 (View on PubMed)

Other Identifiers

UGent2018/0623

Identifier Type: -

Identifier Source: org_study_id