The Effect of Gluten-free Diet on Parkinsonism

Not Applicable

Recruiting

• Conditions: Non-celiac Gluten Sensitivity; Parkinson Disease; Multiple System Atrophy
• Interventions: Other: gluten-free diet

• Registration Number: NCT05238545
• Lead Sponsor: General University Hospital, Prague

Brief Summary

Recent data suggest that the brain-gut axis, chronic intestinal inflammation and microbiome may contribute to the pathogenesis of neurodegenerative diseases with alfa-synucleinopathy, which include Parkinson's disease (PD) and Multiple system atrophy (MSA). Environmental factors e.g. diets, microbiome, metabolites and immune mechanisms may play important role in pathogenesis of these diseases. In the human arm of this project, the investigators will address effects of an anti-inflammatory gluten-free diet (GFD) on motor and non-motor symptoms as well as its effects on immune and metabolomic characteristics in patients with PD and MSA. In the mouse arm, the investigations will focus on the effects of GFD in chronic MPTP-induced mouse model of PD in various settings (e.g. in young or aged animals, with respect to the lengths of exposure to GFD). The chronic MPTP model will be used to assess the effects of GFD on adaptive and immune characteristics, and metabolic signatures. Using germ-free animals, the microbiome-dependency of the GFD-mediated effects may be determined. The anti-inflammatory gluten-free diet and its related mechanisms represent novel, promising and relatively straightforward approach in a search to improve symptoms of PD as well as MSA or even in their prevention.

Detailed Description

This project is based on two research lines, testing the effect of gluten-free diet in a patients with PD and MSA (a human prospective trial) and in the chronic MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD.

Research line 1. Assessments of effects of gluten-free diet (GFD) on clinical symptoms of Parkinson's disease (PD) and multiple system atrophy (MSA) in a prospective, controlled, randomized, rater-blinded human study. The goal of the research line 1 is to assess the effects of 12 months of administration of GFD on clinical symptoms of PD and MSA.

Research line 2. Effects of GFD on the development of PD in the chronic MPTP-induced mouse model of PD. The goal of the research line 2 is to study the effects of GFD in the chronic MPTP-induced mouse model of PD in order to evaluate its impact on clinical development of PD's features as well as immune and metabolomic characteristics that should shed more light on the possible mechanisms and potential novel treatment opportunities.

Study Timeline

• Study Start: 2021-10-01
• Study First Submitted: 2022-02-03
• Study First Submitted QC: 2022-02-03
• Study First Posted: 2022-02-14
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-30
• Last Update Posted: 2022-04-08
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• subjects with establish diagnosis of PD in clinical stage 2-4 of Hoehn&Yahr scale or with establish diagnosis of MSA
• stable treatment for >4 weeks
• willing and able to give informed consent for participation in the study
• male and female subjects, aged 40 years or older
• able to understand and willing to comply with study procedures
• willing to avoid any other diet restrictions
• BMI 18-30

Exclusion Criteria

• concomitant neurological, gastrointestinal or immunological disease
• diet restriction
• dementia affecting compliance
• acute psychiatric symptoms

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PD gluten-free diet group	gluten-free diet	Subjects with PD on gluten-free diet, ie. excluding all gluten-containing food during the day.
MSA gluten-free diet group	gluten-free diet	Subjects with PD on gluten-free diet, ie. excluding all gluten-containing food during the day.

Primary Outcome Measures

Name	Time	Method
Change in severity of the clinical symptoms	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Scored by the MDS-Unified Parkinson's Disease Rating Scale (scores ranging from 0 to 260, higher scores indicate greater impairment) or Unified Multiple System Atrophy Rating Scale (scores ranging from 0 to 104, higher scores indicate greater impairment).

Secondary Outcome Measures

Name	Time	Method
Cognition change	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Scored by Montreal Cognitive Assessment (scores ranging from 0 to 30, lower scores indicate greater impairment).
Change in severity of the autonomic symptoms (Autonomic Scale for Outcomes in Parkinson's Disease)	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Scored by Autonomic Scale for Outcomes in Parkinson's Disease (scores ranging from 0 to 69, higher scores indicate greater impairment).
Quality of sleep change	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Scored by Pittsburgh Sleep Quality Index
Change in spatio temporal parameters of the gait	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Investigated by GaitRite system
Mood change	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Scored by Beck depression inventory (scores ranging from 0 to 63, higher scores indicate greater impairment).
Change in quality of life	Baseline, 1.5, 3, 6, 9, 12 and 13 months	Scored by Quality of life questionnaire (scores ranging from 0 to 100, higher scores indicate greater impairment).

Trial Locations

Locations (1)

GUHPrague; 🇨🇿 Prague, Czechia