Effects of Probiotics on Peripheral Immunity in Parkinson's Disease

NCT05173701 | Unknown

• 1 other identifier: PROB-PD
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

Parkinson's Disease (PD) is a common neurodegenerative disease, with no disease-modifying treatment available, therapy is therefore only symptomatic. The pathophysiology of the disease is still unclear, but inflammatory mechanisms are reported to play a prominent role. An involvement of peripheral adaptive immunity, with an imbalance in T cell subpopulations and in the expression of transcriptional factors (TF) in Cluster of Differentiation (CD) 4 positive T cells has been reported. An initial aggregation of α-synuclein (α-syn) in the gut with subsequent propagation along the vagus nerve to the brain has also been hypothesised. Interestingly, in an α-syn overexpressing murine model, the absence of gut microbiota prevented both microglia activation and motor impairment, pointing to a fundamental role of the microbiota in the development of PD. It has been shown that in Peripheral Blood Mononuclear Cells (PBMC) of PD patients, probiotics modulate the in vitro production of cytokines toward an anti-inflammatory profile. The investigators developed a clinical trial protocol for the evaluation of probiotics' effects on the peripheral immune system profile in Parkinson's Disease patients. ROS, Lymphocyte subpopulations, TF levels in PBMC will be assessed at baseline and after treatment with a mixture of probiotics in PD patients to assess immunomodulatory effects of said treatment. Motor and non-motor symptoms of PD will also be monitored through the trial period.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Probiotics; Immunomodulation; Microbiota

Outcome Measures

Primary Outcomes (7)

• Changes in plasma IFN-γ level

  IFN-γ level will be assessed in plasma samples via ELISA assay.

  Baseline, 12 weeks

• Changes in plasma TNF-α level

  TNF-α level will be assessed in plasma samples via ELISA assay.

  Baseline, 12 weeks

• Changes in plasma IL-4 level

  IL-4 level will be assessed in plasma samples via ELISA assay.

  Baseline, 12 weeks

• Changes in plasma IL-17A level

  IL-17A level will be assessed in plasma samples via ELISA assay.

  Baseline, 12 weeks

• Changes in plasma IL-10 level

  IL-10 level will be assessed in plasma samples via ELISA assay.

  Baseline, 12 weeks

• Changes in plasma Transforming Growth Factor (TGF)-β level

  TGF-β level will be assessed in plasma samples via ELISA assay.

  Baseline, 12 weeks

• Changes in ROS production capacity

  ROS production will be evaluated by the superoxide dismutase-sensitive cytochrome C reduction assay and results of these assays will be expressed as nmol of reduced cytochrome C / 10\^6 cells / 30 min.

  Baseline, 12 weeks

Secondary Outcomes (14)

• Changes in Naive-Memory lymphocytes subpopulations

  Baseline, 12 weeks

• Changes in T helper (Th) lymphocytes subpopulations

  Baseline, 12 weeks

• Changes in Regulatory T cells (Treg) lymphocytes subpopulations

  Baseline, 12 weeks

• Changes in Monocyte subpopulations

  Baseline, 12 weeks

• Changes in NK subpopulations

  Baseline, 12 weeks

Other Outcomes (11)

• Changes in Unified Parkinson's Disease Rating Scale (UPDRS) scores

  Baseline, 6 weeks, 12 weeks

• Changes in Hoehn and Yahr's (H&Y) assessment scale

  Baseline, 6 weeks, 12 weeks

• Changes in Non-Motor Symptoms Scale in Parkinson's disease (NMSS) scores

  Baseline, 6 weeks, 12 weeks

Study Arms (2)

Probiotics

EXPERIMENTAL

Administration of a mixture of probiotics once daily for three months

Dietary Supplement: Probiotics

Placebo

PLACEBO COMPARATOR

Administration of a placebo (maltodextrin) once daily for three months

Dietary Supplement: Placebo

Interventions

Probiotics DIETARY_SUPPLEMENT

Selected probiotics mixture, in powder form, will be administered once daily for three months in the morning.

Probiotics

Placebo DIETARY_SUPPLEMENT

A placebo (2,7g maltodextrin) will be administered once daily for three months in the morning.

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• a diagnosis of Parkinson's Disease;
• a disease duration between 2 and 5 years at baseline

You may not qualify if:

• past or concomitant autoimmune disease
• previous or ongoing immune-modulating or immunosuppressive therapy
• inflammatory bowel diseases, colorectal diseases or past major abdominal or pelvic surgery
• antibiotics therapy up to three months before enrolment
• usage of tube feeding
• known or suspected allergy to any component of the treatment or placebo mixtures
• known and established cognitive decline or any comorbidity preventing reliable completion of trial assessments
• motor fluctuations

Sponsors & Collaborators

• Franca Marino: lead
• Università degli Studi del Piemonte Orientale Amedeo Avogadro: collaborator
• Università degli Studi dell'Insubria: collaborator

Study Sites (1)

Azienda Ospedaliero-Universitaria "Maggiore della Carità"

Novara, 28100, Italy

Location

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MeSH Terms

Conditions

Parkinson Disease

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Franca Marino, Prof.

  Centre for Research in Medical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 8, 2021
• First Posted: December 30, 2021
• Study Start: November 22, 2021
• Primary Completion: September 1, 2022
• Study Completion: January 1, 2023
• Last Updated: June 10, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 6 months after publication of the final results.
• Access Criteria: Requests to access collected data will be reviewed by academic staff at the Centre for Research in Medical Pharmacology, where all data will be stored. Access will be granted to researchers and clinical staff sharing a documented outline of their intended project.

Locations

IT (1)