Fecal Microbiota Transplantation in Parkinson's Disease.

Official title

Fecal Microbiota Transplantation for the Treatment of Patients With Parkinson's Disease.

Overview

Fecal microbiota transplantation (FMT) is an effective and safe treatment for Clostridioides difficile infection (CDI). Though CDI is the only indication for FMT, more and more preliminary data on FMT in neurological disorders are reported due to gut-brain axis. This study is a pilot study to apply FMT on patients with Parkinson's disease (PD). The effect of FMT on motor and non-motor symptoms in PD will be also evaluated.

Detailed description

1. Screening and Enrollment Participants will be recruited from movement disorders clinics at Chang Gung Memorial Hospital (CGMH). Written informed consent will be obtained prior to study participation. Control group participants will undergo the same evaluation protocol as the treatment group, except for fecal microbiota transplantation (FMT). 2. Clinical Assessments Before the baseline visit, participants will complete a 3-day diary documenting motor symptoms, non-motor symptoms, and medication timing. At each visit, neurological examinations and standardized Parkinson's disease (PD) assessments will be performed.

Adverse events (AEs) and serious adverse events (SAEs) will be recorded throughout the study, regardless of causality, and categorized by their relationship to FMT.

Follow-up assessments will be conducted at 1 week, 3 months, and 6 months after FMT. Stool samples will be collected at baseline, 3 months, and 6 months. 3. Donor Screening and Specimen Processing Healthy donors will undergo comprehensive screening, including medical history, risk assessment, and laboratory testing, in accordance with national FMT consensus guidelines. Eligible donors will provide stool samples under standardized conditions.

Samples will be processed at the CGMH microbiota center following established protocols, including preparation for microbiome and metabolite analyses (e.g., short-chain fatty acids) using validated laboratory methods such as gas chromatography-mass spectrometry (GC-MS). Blood samples from participants will also be collected and stored for analysis. 4. Clinical Outcome Measures

Assessments will include:

Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS, on/off medication) Hoehn and Yahr stage Levodopa equivalent daily dose (LEDD) Motor complications (3-day diary) Montreal Cognitive Assessment (MoCA)

Patient-reported outcomes:

Wearing-Off Questionnaire (WOQ-9) Parkinson's Disease Questionnaire (PDQ-39) SENS-PD (non-dopaminergic symptoms) Parkinson's Disease Constipation Questionnaire (PDCQ) 5. FMT Procedure Participants in the treatment group will receive oral vancomycin (125 mg every 6 hours for 3 days) and follow a low-fiber diet prior to FMT. After bowel preparation and a 24-hour washout period, processed donor microbiota will be delivered to the terminal ileum or cecum via ileocolonoscopy. Participants will remain in the right lateral position for at least 30 minutes post-procedure. 6. Specimen Storage All collected specimens will be stored at -80°C at the microbiota center until study completion. Residual samples will be transferred to the institutional biobank or destroyed according to participant consent. 7. Transportation Microbiota preparations will be transported under controlled temperature conditions. For intra-hospital use, samples will be delivered immediately with cold-chain protection. For inter-hospital transport, samples will be frozen at -80°C, shipped on dry ice, and used on the day of arrival or stored for up to 180 days. 8. Quality Control and Follow-up All procedures, including donor selection, sample processing, and patient care, will follow national FMT consensus guidelines. Participants will be monitored at scheduled follow-ups (1 week, 3 months, and 6 months), with additional assessments arranged as needed to ensure safety and data completeness.

Interventions

• Procedure Fecal microbiota transplantation
  All subjects in the treatment group will receive FMT once. Recipients must adhere to a low-fiber diet for three days, and pre-treatment antibiotics with Vancomycin 125 mg, administered as 2 capsules every 6 hours for 3 days. After a 24-hour washout period, they underwent colon preparation followed by FMT. During the procedure, processed 250cc microbiota fluid from healthy donors, provided by the Chang Gung fecal bank, was administered into the terminal ileum or cecum via ileocolonoscopy. To ensu
• Procedure Not received Fecal microbiota transplantation
  All subjects in the Control group will not receive FMT.

Primary outcome measures

• Primary endpoint [Time frame: 6 months]

Secondary outcome measures (1)

• Secondary endpoints [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Clinical diagnosis of idiopathic PD according to UK brain bank criteria.
• PD disease duration ≧5 years to avoid the possible misdiagnosis of atypical parkinsonism.
• Hoehn-Yahr stage 1-4
• Using levodopa in a currently fixed dose.
• Presence of motor complications (motor fluctuation or dyskinesia).
• Written informed consent.
• Age above 18.

Exclusion criteria

• Hoehn-Yahr stage 5. (wheelchair ridden or bedridden due to PD)
• Dementia (MMSE<24), history of encephalitis, or brain organic lesions, including congenital or acquired structural abnormalities (which were detected through brain computed tomography scan or Magnetic Resonance Imaging) may affect neurological function, leading to various neurological deficits and mpairing the cognitive function.
• Current use of probiotics or in the past 3 months.
• For women with childbearing potential. (Female participants are suggested to prevent pregnancy during this trial and undergo a pregnancy test before enrollment.)
• Current need of antibiotics or use in the previous 3 months.
• End stage renal disease caused uremic encephalopathy or liver cirrhosis caused hepatic encephalopathy
• Immunocompromised state.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Savica R, Carlin JM, Grossardt BR, Bower JH, Ahlskog JE, Maraganore DM, Bharucha AE, Rocca WA. Medical records documentation of constipation preceding Parkinson disease: A case-control study. Neurology. 2009 Nov 24;73(21):1752-8. doi: 10.1212/WNL.0b013e3181c34af5. PMID 19933976
• Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997 Aug 28;388(6645):839-40. doi: 10.1038/42166. No abstract available. PMID 9278044
• Hilton D, Stephens M, Kirk L, Edwards P, Potter R, Zajicek J, Broughton E, Hagan H, Carroll C. Accumulation of alpha-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease. Acta Neuropathol. 2014 Feb;127(2):235-41. doi: 10.1007/s00401-013-1214-6. Epub 2013 Nov 17. PMID 24240814
• Shannon KM, Keshavarzian A, Dodiya HB, Jakate S, Kordower JH. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord. 2012 May;27(6):716-9. doi: 10.1002/mds.25020. Epub 2012 May 1. PMID 22550057
• Sprenger FS, Stefanova N, Gelpi E, Seppi K, Navarro-Otano J, Offner F, Vilas D, Valldeoriola F, Pont-Sunyer C, Aldecoa I, Gaig C, Gines A, Cuatrecasas M, Hogl B, Frauscher B, Iranzo A, Wenning GK, Vogel W, Tolosa E, Poewe W. Enteric nervous system alpha-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology. 2015 Nov 17;85(20):1761-8. doi: 10.1212/WNL.0000000000002126. Epu PMID 26475692
• Stokholm MG, Danielsen EH, Hamilton-Dutoit SJ, Borghammer P. Pathological alpha-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann Neurol. 2016 Jun;79(6):940-9. doi: 10.1002/ana.24648. Epub 2016 Apr 9. PMID 27015771
• Liu B, Fang F, Pedersen NL, Tillander A, Ludvigsson JF, Ekbom A, Svenningsson P, Chen H, Wirdefeldt K. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology. 2017 May 23;88(21):1996-2002. doi: 10.1212/WNL.0000000000003961. Epub 2017 Apr 26. PMID 28446653
• Svensson E, Horvath-Puho E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sorensen HT. Vagotomy and subsequent risk of Parkinson's disease. Ann Neurol. 2015 Oct;78(4):522-9. doi: 10.1002/ana.24448. Epub 2015 Jul 17. PMID 26031848

Identifiers

NCT: NCT07597421 · 202401790A0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗