A Trial of Fecal Microbiome Transplantation in Parkinson's Disease Patients

A Randomized, Double Blind, Placebo Controlled Multicenter Trial of Fecal Microbiome Transplantation Safety and Efficacy for Parkinson's Disease Patients with Abnormal Gut Microbiota Composition

48 PD patients (age 35-75y; H&Y 1-3) testing positive in a stool PD-dysbiosis test will be randomized in a 2:1 ratio to receive either donor FMT or their own stool through intracaecal infusion. The main outcome measure will be the sum of MDS-UPDRS I-III at 6 months to cover motor and non-motor symptom changes. A wide array of secondary clinical outcome measures will be assessed longitudinally and a large array of measurements, biospecimens (stool, urine, blood, colonic biopsies), and imaging data will be collected for further analysis at baseline, 1, 6, and 12 months.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: Administration of donor FMT; Other: Administration of placebo

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital
  • Lahti, Finland
    • Päijät-Häme Central Hospital
  • Tampere, Finland
    • Tampere University Hospital
  • Turku, Finland
    • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of idiopathic PD (Clinically Probable PD)
• H&Y OFF 1-3 at Baseline Visit

Exclusion Criteria:

1. Chronic gastrointestinal disease (IBS allowed, celiac disease allowed if on gluten free diet, gastritis allowed)
2. Any previous major gastrointestinal surgery that may alter gastrointestinal physiology
3. Any abdominal surgery in the last 3 months
4. Major genital and/or rectum prolapse
5. Active autoimmune disease
6. Active cancer within 5 years (allowed: basalioma and successfully removed carcinoma in situ)
7. Immune deficiency
8. HIV infection
9. Antibiotic use in last 3 months before baseline visit
10. Dementia as indicated by Moca <21p
11. Psychosis
12. Active significant impulse control disorder (by interview and medical records)
13. Major depression as indicated by BDI-II >28
14. Pregnancy
15. Alcohol or drug abuse
16. Negative dysbiosis test result
17. Iodine allergy
18. Deep brain stimulation or Duodopa/Lecigon treatment
19. Inability to interrupt regular use of NSAIDs for at least one month before permeability assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donor FMT; FMT from a healthy donor	Other: Administration of donor FMT; Intracaecal infusion of FMT
Placebo Comparator: Placebo; NaCl + glycerol mixture (carrier solution of FMT arm)	Other: Administration of placebo; Intracaecal infusion of carrier solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of the sum of MDS-UPDRS I-III from baseline	Sum of Movement Disorder Society Unified Parkinson's Disease Rating Scale sum of parts I, II, and III (in OFF state); Min 0 - Max 236 points (higher points indicating worse symptoms) will be determined at baseline and at 6 months after intervention. The difference between these values will be the primary outcome measure; Min 0 - Max 236 points (higher points indicating stronger improvement)	at 6 months post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of MDS-UPDRS III from baseline	Movement Disorder Society Unified Parkinson's Disease Rating Scale part III (in OFF state); Min 0 - Max 132 points (higher points indicating worse symptoms) will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 132 points (higher points indicating stronger improvement)	at 6 and 12 months post intervention
Change of MDS-UPDRS IV from baseline	Movement Disorder Society Unified Parkinson's Disease Rating Scale part IV; Min 0 - Max 132 points (higher points indicating worse symptoms) will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 24 points (higher points indicating stronger improvement)	at 6 and 12 months post intervention
Change of Timed UP GO test from baseline	measured in seconds, higher value indicating worse clinical symptoms expressed as difference between 6 and 12 month post intervention and baseline, higher value indicating stronger improvement	at 6 and 12 months post intervention
Change of MDS-UPDRS I from baseline	Movement Disorder Society Unified Parkinson's Disease Rating Scale part I; Min 0 - Max 52 points (higher points indicating worse symptoms) will be determined at baseline and at 6 months after intervention. The difference between these values will be calculated; Min 0 - Max 52 points (higher points indicating stronger improvement)	at 6 and 12 months post intervention
Change of NMSS from baseline	Non-motor symptom scale (0-360 points, higher points indicating worse symptoms) will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 360 points (higher points indicating stronger improvement)	at 6 and 12 months post intervention
Change in gut permeability, motility and volume from baseline	Gut permability is studied using the Iohexole test.Motility and volume is studied using radio-opaque markers and volume measurments from abdominal CT scans	at 6 months
Change of fecal and blood markers from baseline	Shotgun metagenomics based taxonomic microbiota survey, metabolomics, inflammatory markers, DNA methylation	whole study period
Change of BDI-II from baseline	Beck Depression Inventory II (0-63 points, higher points indicating worse symptoms) will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 63 points (larger decrease indicating stronger improvement)	at 6 and 12 months post intervention
Change of BAI from baseline	Beck Anxiety inventory will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 63 points (larger decrease indicating stronger improvement)	at 6 and 12 months post intervention
Change of RBDSQ from baseline	REM sleep behavior disorder screening questionnaire will be determined at baseline and at 6 and 12 months after intervention.	at 6 and 12 months after intervention
Change of MoCa from baseline	MONTREAL COGNITIVE ASSESSMENT (0-30 points, higher points indicating less symptoms) will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 30 points (higher increase indicating stronger improvement)	at 6 and 12 months post intervention
Change of IBS-SSS from baseline	The irritable bowel severity scoring system will be determined at baseline and follow-up	at 6 and 12 months after intervention
Change of PDQ39 index from baseline	Parkinson's Disease Questionnaire 39 index (0-100 points, higher points indicating worse quality of life) will be determined at baseline and at 6 and 12 months after intervention. The difference between these values will be calculated; Min 0 - Max 100 points (larger decrease indicating stronger improvement)	at 6 and 12 months post intervention

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: Turku University Hospital; University of Aarhus; University of Helsinki; Tampere University Hospital; Central Hospital of Paijat-Hame
• Investigators: Principal Investigator: Filip Scheperjans, MD, Helsinki University Central Hospital

Publications and helpful links

General Publications

• Scheperjans F, Levo R, Bosch B, Laaperi M, Pereira PAB, Smolander OP, Aho VTE, Vetkas N, Toivio L, Kainulainen V, Fedorova TD, Lahtinen P, Ortiz R, Kaasinen V, Satokari R, Arkkila P. Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2024 Sep 1;81(9):925-938. doi: 10.1001/jamaneurol.2024.2305.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2021
• Primary Completion (Actual): December 27, 2022
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 17, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: FMT; Parkinson's disease; microbiota; gut-brain axis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: PD-FMT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Raw sequencing reads will be uploaded to the European Nucleotide Archive. Upon reasonable request and execution of a data transfer agreement we will share de-identified clinical data and metadata in the range that is permitted by local legislation.
• IPD Sharing Time Frame: After publication of the results for indeterminate time.
• IPD Sharing Access Criteria: Upon reasonable request and execution of a data transfer agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No