Clinical trial NCT06463769: Impact of Diet on the Microbiome-Immune-Brain Axis in Parkinson's Disease
Official title: "Impact of Diet on the Microbiome-Immune-Brain Axis in Parkinson's Disease" as Part of the Collaborative Research Center 1697 "Targeting the Microbiome-Immune-Brain Interaction in Neurodegeneration"
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: New Nordic Diet
Parkinson's Disease
Microbiome-Immune-Brain axis
Lead sponsor: University of Kiel
Sponsor class: OTHER
Collaborators: name: University Hospital Schleswig-Holstein
First posted: 2024-06-18
Enrollment: 75
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: Patients with prodromal PD receiving nutritional intervention Arm 2: Patients with clinical PD receiving nutritional intervention Arm 3: Patients with clinical PD receiving standard of care (control)
Primary purpose: TREATMENT

Brief summary: Habitual adherence to a predominantly plant-based diet, rich in low-processed food (LPF) has been associated with a reduced risk for development and slower progression of Parkinson's Disease (PD). This could be due to neuroprotective effects by modulation of the gut microbiota and decreased neuronal and metabolic inflammation. So far, the effect of a predominantly plant-based LPF-diet on the microbiome-immune-brain axis in patients with PD remains unknown. In addition, the influence of dietetic measures on the gut microbiome is variable and may depend on (long-term) adherence as well as on PD-specific factors and lifestyle.

The investigators hypothesize that compared to an average German diet, the predominantly plant-based New Nordic LPF-diet, as a culturally adapted diet, which is rich in fermentable fiber and phytochemicals, will have beneficial effects on the gut microbiome of patients with PD by increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria (primary outcome) and will improve gut motility, metabolic resilience, and inflammation (secondary outcomes). Furthermore, the investigators postulate that a patient-centered dietary intervention program, including a multifaceted patient education and supported by a web-application, will lead to high adherence as a key determinant of long-term changes in the gut microbiome. This dietary intervention will be accepted by patients as a low-threshold treatment that balances personal benefits, therapeutic barriers and ethical concerns of early risk disclosure in PD.

Detailed description: In a pilot-intervention study, our project will:

* develop a practical, low-threshold diet intervention for patients with prodromal and clinical PD. Adherence will be promoted (i) by a patient-oriented approach, (ii) by implementation of the predominantly plant-based New Nordic LPF-diet that is scientifically-based, culturally adapted, sustainable and culinary and (iii) by an innovative web-application.
* investigate the acute effects of the predominantly plant-based New Nordic LPF -diet on the microbiome (abundance of SCFA-producing bacteria), gastrointestinal motility, inflammation as well as metabolic and Parkinson-specific clinical outcomes in individuals with prodromal and clinical PD.
* investigate potential determinants of long-term changes in the gut microbiome (e.g. dietary adherence, gastrointestinal motility, meal timing and frequency), and factors associated with a high adherence (e.g. acceptance of diet as therapeutic intervention in the prodromal phase, health-related quality of life).

The patient-centered intervention program will be tailored to individual needs and preferences of individuals with prodromal and clinical PD. It will be designed to impart knowledge (e.g. on sustainability and health effects) and food literacy (e.g. food merchandize and culinary skills) in group meetings and culinary medicine workshops. Recipe suggestions and shopping guides will consider individual abilities and needs and a web-application is used for information, increasing self-efficacy, motivation, and monitoring. To ensure an easy integration of the diet into everyday life, partners will be included in the program, if applicable. Moreover, cultural preferences as well as financial resources will be considered. Regular feedback using statistics on nutrient intake and overall progress will be implemented to encourage adherence.

Eligibility criteria: Inclusion Criteria:

* patients with probable prodromal PD (according to predefined criteria)
* patients with clinical PD with slight to moderate disease severity (Hoehn \& Yahr 1-2.5)
* habitual Western Diet (≥30% of energy intake from ultra-processed food)

Exclusion Criteria:

* current adherence to a plant-based diet
* food allergies or intolerances
* significant diseases of the gastrointestinal system (e.g. celiac disease) or central nervous system, diabetes mellitus
* underweight (BMI \<18.5 kg/m2)
* active smoking
* expected changes in medication or antibiotic treatment during the intervention

Primary outcomes:
measure: abundance of key SCFA-producing gut bacteria
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
Secondary outcomes:
measure: systemic inflammation markers
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: metabolic resilience
timeFrame: pre vs. post intervention (8 weeks)
measure: gastrointestinal peptide-hormones
timeFrame: pre vs. post intervention (8 weeks)
measure: energy balance
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: energy partitioning
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
Other outcomes:
measure: clinical motor symptoms
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: clinical non-motor symptoms
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: gastric emptying
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: gastrointestinal transit time
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: gut motility
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: dietary adherence via serum markers
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: dietary adherence via healthy Nordic food Index
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: food literacy effectiveness
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: patient acceptance
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
measure: patient quality of life
timeFrame: pre vs. post intervention (8 weeks) + pre intervention vs. follow-up 6 months after completion of intervention
Locations:
city: Kiel
country: Germany
facility: Institute of Human Nutrition
city: Kiel
country: Germany
facility: Kiel University, University Hospital Schleswig-Holstein
Study officials:
affiliation: Kiel University
name: Anja Bosy-Westphal, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kiel University, University Hospital Schleswig-Holstein
name: Eva Schäffer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aho VTE, Houser MC, Pereira PAB, Chang J, Rudi K, Paulin L, Hertzberg V, Auvinen P, Tansey MG, Scheperjans F. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease. Mol Neurodegener. 2021 Feb 8;16(1):6. doi: 10.1186/s13024-021-00427-6.
citation: Solch RJ, Aigbogun JO, Voyiadjis AG, Talkington GM, Darensbourg RM, O'Connell S, Pickett KM, Perez SR, Maraganore DM. Mediterranean diet adherence, gut microbiota, and Alzheimer's or Parkinson's disease risk: A systematic review. J Neurol Sci. 2022 Mar 15;434:120166. doi: 10.1016/j.jns.2022.120166. Epub 2022 Jan 26.
citation: Maraki MI, Yannakoulia M, Stamelou M, Stefanis L, Xiromerisiou G, Kosmidis MH, Dardiotis E, Hadjigeorgiou GM, Sakka P, Anastasiou CA, Simopoulou E, Scarmeas N. Mediterranean diet adherence is related to reduced probability of prodromal Parkinson's disease. Mov Disord. 2019 Jan;34(1):48-57. doi: 10.1002/mds.27489. Epub 2018 Oct 10.