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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Parkinson Disease

Intervention / Treatment
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* Other: Administration of donor FMT
* Other: Administration of placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic PD (Clinically Probable PD) H&Y OFF 1-3 at Baseline Visit Exclusion Criteria: Chronic gastrointestinal disease (IBS allowed, celiac disease allowed if on gluten free diet, gastritis allowed) Any previous major gastrointestinal surgery that may alter gastrointestinal physiology Any abdominal surgery in the last 3 months Major genital and/or rectum prolapse Active autoimmune disease Active cancer within 5 years (allowed: basalioma and successfully removed carcinoma in situ) Immune deficiency HIV infection Antibiotic use in last 3 months before baseline visit Dementia as indicated by Moca <21p Psychosis Active significant impulse control disorder (by interview and medical records) Major depression as indicated by BDI-II >28 Pregnancy Alcohol or drug abuse Negative dysbiosis test result Iodine allergy Deep brain stimulation or Duodopa/Lecigon treatment Inability to interrupt regular use of NSAIDs for at least one month before permeability assessments

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, FMT, microbiota, gut-brain axis