Clinical trial NCT05238545: The Effect of Gluten-free Diet on Parkinsonism
Official title: The Effect of Gluten-free Diet on Clinical Symptoms, Immune Parameters and Metabolome in Neurodegenerative Diseases With Alfa-synucleinopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Multiple System Atrophy
Non-celiac Gluten Sensitivity
Keywords: Parkinson Disease
Multiple system atrophy
Gluten-free Diet
Lead sponsor: General University Hospital, Prague
Sponsor class: OTHER
Collaborators: name: Czech Academy of Sciences
First posted: 2022-02-14
Enrollment: 90
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study groups in PD and MSA group with gluten-free diet and on regular gluten-containing diet. Randomization: patients will be randomized by diagnosis, age and disease duration, a numbered envelope in 1:1 ration to gluten-free diet group and regular gluten-containing diet group will be used.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in severity of the clinical symptoms
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
Secondary outcomes:
measure: Cognition change
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
measure: Change in severity of the autonomic symptoms (Autonomic Scale for Outcomes in Parkinson's Disease)
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
measure: Change in spatio temporal parameters of the gait
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
measure: Quality of sleep change
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
measure: Mood change
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
measure: Change in quality of life
timeFrame: Baseline, 1.5, 3, 6, 9, 12 and 13 months
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: GUHPrague
Study officials:
References: