Optimizing Protein Patterns for Skeletal Muscle Preservation and Sleep in the Medical Management of Parkinson Disease

Study Overview
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Brief Summary
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The purpose of this pilot study is to generate preliminary data on the impact of the dietary protein pattern on markers of skeletal muscle health and drug efficacy in Parkinson disease.

Detailed Description
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Parkinson's disease (PD) is a complex neurological disease that affects  6.1 million people worldwide - mostly older adults >60 years. The most effective treatment for PD is dopaminergic therapy, particularly levodopa (Ldopa). People with PD have variable responses to Ldopa, including degrees of motor fluctuations (MF) throughout the day. The half-life of Ldopa is  1.5 h and therefore, dosage and timing are essential to mitigate MF. Ldopa is a large neutral amino acid (LNAA), and the bioavailability of Ldopa is compromised when simultaneously ingested with LNAA (e.g., leucine). Both Ldopa and LNAAs from food are absorbed through the same intestinal transporter, but LNAAs from food are preferentially absorbed by the enterocyte, limiting the bioavailability of Ldopa. Thus, the scientific community often recommends the protein-redistribution diet (PRD). With PRD, patients limit protein (<10 g) at the desired time of medication efficacy (daytime) and meet their protein needs during the evening meal ( 70+g). There are deleterious implications of the PRD for older adults with PD; consumption of >30 g of protein, in a single meal, will not sufficiently increase muscle protein synthesis. Additionally, the impact of the PRD on skeletal muscle quality and function has not been determined, and it is unclear, based on prior studies, whether the PRD enhanced drug absorption. Therefore, the objective of this study is to address these gaps in knowledge. This study will quantify the effects of dietary protein pattern on skeletal muscle in PD; determine the effects of dietary protein pattern on sleep quality in PD. This study is an acute, 5-week, crossover intervention with PD participants randomly assigned to first adhere to either the PCD or PRD. Participants will receive diet prescriptions and meal plans for their respective diet, and outcome measures will be assessed at days 0, 14, 21, and 35.

Official Title
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Optimizing Protein Patterns for Skeletal Muscle Preservation and Sleep in the Medical Management of Parkinson Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Behavioral: Protein Redistribution Diet
* Behavioral: Protein Consistent Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of idiopathic PD for 5 or more years 45 years or older On a stable levodopa regimen for 3 or more months Self-reported to experience motor fluctuations Exclusion Criteria: Following a specific diet that would preclude participation Renal disease Deep brain stimulation Known narcolepsy Untreated sleep apnea Any condition that, in the opinion of the investigator, will preclude the participant from successfully or safely completing study procedures

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: PD participants randomly assigned to first adhere to either the Protein Consistent Diet or Protein Redistribution Diet for 2 weeks. Participants will enter a 1-week washout period between the diets where they follow their typical diet and then follow the other diet prescription for 2 weeks.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Protein Redistribution Diet<br>PD participants may first be randomized to follow the Protein Redistribution Diet followed by the Protein Consistent Diet. | Behavioral: Protein Redistribution Diet<br>* PD participants will be instructed by a Registered Dietitian to consume 10 grams or less of protein until their evening meal. They will then consume a high protein evening meal to meet their protein needs. They will receive one-on-one education and supportive materials to follow diet plan.<br>* Other names: PRD;|
| Active Comparator: Protein Consistent Diet<br>PD participants may first be randomized to follow the Protein Consistent Diet followed by the Protein Redistribution Diet. | Behavioral: Protein Consistent Diet<br>* PD participants will be instructed by a Registered Dietitian to consume 20-30 grams of protein per meal. They will receive one-on-one education and supportive materials to follow diet plan.<br>* Other names: PCD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in markers of skeletal muscle metabolism GDF15 | Serum Growth Differentiation Factor 15 (GDF15) | Baseline to 5 weeks | 
| Change in markers of skeletal muscle metabolism FGF21 | Serum Fibroblast Growth Factor 21 (FGF21) | Baseline to 5 weeks | 
| Change in handgrip strength | Handgrip strength assessed via digital dynamometer | Baseline to 5 weeks | 
| Change in sleep efficiency | Sleep efficiency assessed via actigraphy | Baseline to 5 weeks | 
| Change in motor symptoms | Motor symptoms assessed via the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II. Part II ranges from 0-52 with higher scores indicating greater symptom severity. | Baseline to 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in physical activity | Physical activity assessed via actigraphy | Baseline to 5 weeks | 
| Change in total Parkinson symptoms | Parkinson-related symptoms assessed by total MDS-UPDRS score | Baseline to 5 weeks. Total score ranges from 0-260 with higher scores indicating greater symptom severity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Diet, Protein, Skeletal Muscle, Sleep