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Fecal Microbiota Transplantation for Parkinson's Disease

Primary Purpose

Parkinson Disease

Status

Completed

Phase

Not Applicable

Locations

Belgium

Study Type

Interventional

Intervention

Donor FMT

Autologous FMT

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinson's disease, Fecal microbiota transplantation, Microbiome, Gut-brain axis

Eligibility Criteria

50 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Ghent University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Treatment group: Donor FMT

Control group: Autologous FMT

Arm Description

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

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

Outcomes

Primary Outcome Measures

Changes in clinical symptoms as scored on the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale)

The MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) has four parts: Part I (non-motor experiences of daily living; 13 items), Part II (motor experiences of daily living; 13 items), Part III (motor examination; 33 scores based on 18 items, several with right, left or other body distribution scores) and Part IV (motor complications; 6 items). Each item has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Part III will be clinically scored in an OFF-medication state. Subscales are analyzed separately. References: Goetz, C. et al. Movement Disord 22, 41-47 (2007). Goetz, C. et al. Movement Disord 23, 2129-2170 (2008).

Secondary Outcome Measures

Changes in non-motors symptoms as scored on the Non-motor symptoms scale for Parkinson's disease (NMSS)

Non-motor symptoms scale for Parkinson's disease (NMSS). Non-motor symptoms are assessed over the last month. Each symptom is scored with respect to: Severity: 0 = None; 1 = Mild: symptoms present but causes little distress or disturbance to patient; 2 = Moderate: some distress or disturbance to patient; 3 = Severe: major source of distress or disturbance to patient. Frequency: 1 = Rarely (<1/wk); 2 = Often (1/wk); 3 = Frequent (several times per week); 4 = Very Frequent (daily or all the time). NMSS contains nine dimensions: cardiovascular (2 items), sleep/fatigue (4 items), mood/cognition (6 items), perceptual problems (3 items), attention/memory (3 items), gastrointestinal (3 items), urinary (3 items), sexual function (2 items), and miscellaneous (4 items). Subscores are calculated through multiplication of frequency x severity. Total score is calculated by adding all subscores, range 0-360. Reference: Chaudhuri, K. R. et al. Mov. Disord. 22, 1901-11 (2007).

Changes in quality of life as scored on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39)

Parkinson's Disease Quality of Life Questionnaire. All 39 questions are coded in the same way: 0 = Never; 1 = Occasionally; 2 = Sometimes; 3 = Often; 4 = Always (or cannot do at all, if applicable). The different dimensions are mobility (10 items), activities of daily living (6 items), emotional well being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). Each dimension is calculated as a scale from 0 to 100 (0 = no problem at all; 100 = maximum level of problem). Formula for scoring each dimension = (sum of scores of each question in dimension)/ (4 x number of questions in dimension) x 100. The Single Index score: PDQ-SI= summing the eight dimensions and then dividing by eight. Reference: Jenkinson, C., Fitzpatrick, R., Peto, V., Greenhall, R. & Hyman, N. Age Ageing 26, 353-7 (1997).

Changes in cognition as scored on the Montreal Cognitive Assessment (MoCA)

The Montreal Cognitive Assessment (MoCA) assesses several cognitive domains: short-term memory, visuospatial abilities, executive functions, attention, concentration, working memory, language, orientation to time and place. MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Reference: Nasreddine, Z. et al. J Am Geriatr Soc 53, 695-699 (2005).

Number of participants with a change in required anti-PD symptomatic or levodopa therapy

Changes in gastrointestinal symptoms as assessed by the Rome IV questionnaire

The Rome IV criteria for functional constipation and irritable bowel syndrome are assessed to evaluate potential change in gastrointestinal symptoms following the fecal microbiota transplantation.

Full Information

NCT ID

NCT03808389

First Posted

June 22, 2018

Last Updated

January 27, 2023

Sponsor

University Ghent

Collaborators

University Hospital, Ghent, the Flanders Institute for Biotechnology, Research Foundation Flanders, Vlaamse Parkinson Liga, Parkili

1. Study Identification

Unique Protocol Identification Number

NCT03808389

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

December 1, 2020 (Actual)

Primary Completion Date

December 9, 2022 (Actual)

Study Completion Date

December 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Ghent

Collaborators

University Hospital, Ghent, the Flanders Institute for Biotechnology, Research Foundation Flanders, Vlaamse Parkinson Liga, Parkili

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

Keywords

Parkinson's disease, Fecal microbiota transplantation, Microbiome, Gut-brain axis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

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).

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

49 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment group: Donor FMT

Arm Type

Experimental

Arm Description

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

Arm Title

Control group: Autologous FMT

Arm Type

Sham Comparator

Arm Description

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

Intervention Type

Other

Intervention Name(s)

Donor FMT

Other Intervention Name(s)

FMT with donor stool

Intervention Description

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

Intervention Name(s)

Autologous FMT

Other Intervention Name(s)

FMT with own stool

Intervention Description

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.

Primary Outcome Measure Information:

Title

Changes in clinical symptoms as scored on the MDS-UPDRS (Movement Disorder Society - Unified Parkinson's Disease Rating Scale)

Description

Time Frame

3 months, 6 months, 12 months

Secondary Outcome Measure Information:

Title

Changes in non-motors symptoms as scored on the Non-motor symptoms scale for Parkinson's disease (NMSS)

Description

Time Frame

3 months, 6 months, 12 months

Title

Changes in quality of life as scored on the Parkinson's Disease Quality of Life Questionnaire (PDQ-39)

Description

Time Frame

3 months, 6 months, 12 months

Title

Changes in cognition as scored on the Montreal Cognitive Assessment (MoCA)

Description

Time Frame

3 months, 6 months, 12 months

Title

Number of participants with a change in required anti-PD symptomatic or levodopa therapy

Time Frame

3 months, 6 months, 12 months

Title

Changes in gastrointestinal symptoms as assessed by the Rome IV questionnaire

Description

The Rome IV criteria for functional constipation and irritable bowel syndrome are assessed to evaluate potential change in gastrointestinal symptoms following the fecal microbiota transplantation.

Time Frame

3 months, 6 months, 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patrick Santens, MD, PhD

Organizational Affiliation

Ghent University, Ghent University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ghent University Hospital

City

Ghent

ZIP/Postal Code

9000

Country

Belgium

12. IPD Sharing Statement

Plan to Share IPD

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Fecal Microbiota Transplantation for Parkinson's Disease

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