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

The Effect of Gluten-free Diet on Clinical Symptoms, Immune Parameters and Metabolome in Neurodegenerative Diseases With Alfa-synucleinopathy

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Multiple System Atrophy; Non-celiac Gluten Sensitivity
• Intervention / Treatment: Other: gluten-free diet

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 Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hana Brožová, MD, PhD; Phone Number: 00420 224965539; Email: hana.brozova@lf1.cuni.cz
• Study Contact Backup: Name: Kamila Poláková, MD, PhD; Phone Number: 00420 224965539; Email: kamila.polakova@vfn.cz

Study Locations

• Czechia
  • Prague, Czechia
    • Recruiting
    • GUHPrague
    • Contact: Hana Brožová, MD; Phone Number: 00420 224965539; Email: hana.brozova@lf1.cuni.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD gluten-free diet group; Subjects with PD on gluten-free diet, ie. excluding all gluten-containing food during the day.	Other: gluten-free diet; Diet excluding foods containing gluten.
No Intervention: PD gluten-containing diet group; Subjects with PD on regular, gluten-containing diet, i.e. no restrictions during eating.
Experimental: MSA gluten-free diet group; Subjects with PD on gluten-free diet, ie. excluding all gluten-containing food during the day.	Other: gluten-free diet; Diet excluding foods containing gluten.
No Intervention: MSA gluten-containing diet group; Subjects with MSA on regular gluten-containing diet, i.e. no restrictions during eating.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in severity of the clinical symptoms	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).	Baseline, 1.5, 3, 6, 9, 12 and 13 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: General University Hospital, Prague
• Collaborators: Czech Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Parkinson Disease; Multiple system atrophy; Gluten-free Diet
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Parkinson Disease; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome
• Other Study ID Numbers: NU21-04-00443

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No