Mediterranean Diet Intervention to Improve Gastrointestinal Function in Parkinson's Disease a Randomized, Controlled, Clinical Trial

Study Overview
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Brief Summary
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This is a 10-week randomized, controlled study to investigate the effect of a Mediterranean diet intervention on gastrointestinal function in Parkinson's disease. After a 2-week run-in period, participants will be instructed to receive standard of care for constipation or receive standard of care + follow a Mediterranean diet for 8 weeks and answer daily and weekly questionnaires. Nutritional and neurological evaluations and stool samples will be collected at 0, 4 and 8 weeks.

Official Title
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Mediterranean Diet Intervention to Improve Gastrointestinal Function in Parkinson's Disease: a Randomized, Controlled, Clinical Trial

Conditions
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Parkinson Disease

Intervention / Treatment
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* Other: Standard of care + Mediterranean diet (intervention)
* Other: Standard of care (control)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician-diagnosed Parkinson's disease aged 40-85 years Drug naïve or on stable dosage of Parkinson's medications with no plans to change for the duration of the study protocol Hoehn & Yahr stage =<2.5 in the clinical ON state Constipation syndrome scores >=2.0 based on the GSRS Consume <20 grams of fiber daily based on the Block Fruit/Vegetable/Fiber screener Able to complete informed consent in English Willing to maintain habitual diet through the pre-baseline period. Willing to make dietary changes to follow a Mediterranean diet and/or receive standard of care for constipation during the intervention period. Willing to complete daily and weekly questionnaires and 12 dietary recalls over approximately 10 weeks. Able to provide stool samples during the study collection periods. Willing to avoid strenuous exercise and alcohol such as beer, wine, and cocktails 24 hours prior to each of the 3 study visits. Able to fast (no food or drink, except water, or decaf tea) at least 12 hours before each study visit Willing to discontinue taking prebiotic, herbal, or high-dose vitamin or mineral supplements that may impact inflammation during the pre-baseline period and throughout the study protocol. Exclusion Criteria: Atypical or secondary Parkinsonism Underweight (BMI <18.5) History of deep brain stimulation (DBS) surgery Regular use of enemas or suppositories to alleviate constipation (e.g., >1 time per week) Use of another investigational product within 3 months of the screening visit Antibiotic or probiotic supplement use within 2 months from the day of stool collection Currently being treated for a physician-diagnosed GI disease or condition other than constipation, irritable bowel disease, gastroparesis, reflux or diverticular disease

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double-blind, controlled parallel study in which participants either follow a Mediterranean diet or their habitual diet for an 8-week intervention.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard of Care + Mediterranean Diet<br>Participants will be given standard of care for constipation (handout) plus individualized diet education on the Mediterranean diet and instructed to follow the diet during the 8-week intervention period. Diet education will be administered by a study dietitian and followed with weekly phone calls to ensure compliance, improve adherence to the diet and monitor for adverse events. | Other: Standard of care + Mediterranean diet (intervention)<br>* Participants will receive a constipation management handout that is distributed regularly to patients who present with constipation symptoms at an outpatient neurology clinic. The handout recommends increasing fluids daily, as well as increasing physical activity and dietary fiber intake. Laxative medications and recommendations for usage are included. Participants will be instructed to include the following in their diet: a) abundant use of olive oil for cooking and dressing dishes; b) consume ≥2 daily servings of vegetables; c) ≥2-3 daily serving of fruits; d) ≥3 weekly servings of legumes; e) ≥3 weekly servings of fish/seafood; f) ≥3 weekly serving of nuts/seeds; g) select white instead of red or processed meats; h) cook at least twice a week with sofrito. Limit consumption of cream, butter, processed meat, sugared beverages, industrial bakery products and desserts, and French fries or chips. For usual drinkers, the main source of alcohol should be wine.<br>|
| Active Comparator: Standard of Care<br>Participants will be given standard of care for constipation (handout) to utilize during the 8-week intervention period. A study dietitian will follow up with weekly phone calls to support adherence and monitor for adverse events. | Other: Standard of care (control)<br>* Participants will receive a constipation management handout that is distributed regularly to patients who present with constipation symptoms at an outpatient neurology clinic. The handout recommends increasing fluids daily, as well as increasing physical activity and dietary fiber intake. Laxative medications and recommendations for usage are included.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GSRS Constipation Syndrome Score | The difference between mean change (final - baseline) in constipation syndrome scores for the Med diet versus control diet. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool Frequency | Compare the number of stools between the intervention and control groups | Each week up to 10 weeks | 
| Stool Form | Compare stool form, as measured by the Bristol Stool Form Scale (BSFS), between the intervention and control groups. The BSFS is scored between 1 (hard stool) - 7 (liquid stool). | Each day up to 10 weeks | 
| Laxative Usage | Compare number of days using laxative medications between the intervention and control groups. | Each week up to 10 weeks | 
| Digestive Health | Weekly GI symptoms assessed using the Gastrointestinal Symptom Rating Scale (GSRS). The GSRS consists of 15 questions related to 5 syndromes, constipation, diarrhea, reflux, abdominal pain, and indigestion. Symptoms are scored 1=no discomfort to 7=very severe discomfort. Scores from each of the 15 questions are summed for the total GSRS score. | Every week up to 10 weeks | 
| Quality of Life Related to Digestive Health | Weekly GI experiences assessed using an in-house Digestion-Associated Quality of Life questionnaire. | Every week up to 10 weeks | 
| Fecal Microbial Diversity | Changes in fecal microbial composition and diversity (i.e. alpha and beta diversity) will be assessed. | Baseline (Week 0); Midpoint (Week 4); Final (Week 8) | 
| Fecal Microbial Quantitative Polymerase Chain Reaction (qPCR) | Changes in fecal microbial composition to quantify bacterial species of interest (e.g., F. prausnitzii, Prevotella, Roseburia, Bilophila, Akkermansia, etc.) will be assessed. | Baseline (Week 0); Midpoint (Week 4); Final (Week 8) | 
| Intestinal Inflammation and Permeability | Changes in fecal calprotectin and zonulin will be assessed using enzyme-linked immunosorbent assay | Baseline (Week 0); Midpoint (Week 4); Final (Week 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mediterranean diet, Microbiome, Constipation, Inflammation