The Effect of Gluten-free Diet on Parkinsonism (GFREEPARK)

General University Hospital, Prague

Status: Enrolling

Conditions: Multiple System Atrophy; Parkinson Disease; Non-celiac Gluten Sensitivity

Treatments: Other: gluten-free diet

Study type: Interventional

Funder types: Other

Identifiers

NCT05238545

NU21-04-00443

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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90 participants in 4 patient groups

PD gluten-free diet group

Experimental group

Description:

Subjects with PD on gluten-free diet, ie. excluding all gluten-containing food during the day.

Treatment:

Other: gluten-free diet

PD gluten-containing diet group

No Intervention group

Description:

Subjects with PD on regular, gluten-containing diet, i.e. no restrictions during eating.

MSA gluten-free diet group

Experimental group

Description:

Subjects with PD on gluten-free diet, ie. excluding all gluten-containing food during the day.

Treatment:

Other: gluten-free diet

MSA gluten-containing diet group

No Intervention group

Description:

Subjects with MSA on regular gluten-containing diet, i.e. no restrictions during eating.