Acute Effects of Medium Chain Triglyceride (MCT) Nutritional Ketosis on Parkinson's Disease (PD) Symptoms and Biomarkers (MCT-PD)
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease; Ketosis
Intervention: Liquigen MCT oil; Standard American Diet
Intervention description: MCT oil is a nutritional supplement. The Ketogenic diet restricted carbohydrates to reach 80/5-10/10-15 (lipid:carb:protein daily energy) values; Standard diet with macronutrient composition lipid 35%, protein 10-15%, carbohydrate 50-55%
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 21.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: MCT Medium Chain Triglyceride; Ketogenic Diet; Nutritional Ketosis; Parkinson's Biomarkers

Summary:

      Background:

      The ketogenic diet uses fats as a person's major energy source rather than carbohydrates.
      There is increasing interest in using this diet to treat neurodegenerative disorders like
      Parkinson's disease. Researchers want to learn more about the ketogenic diet before
      recommending this diet in clinical practice.

      Objective:

      To study the effects of a ketogenic diet for someone with PD.

      Eligibility:

      People over age 50 with mild to moderate PD.

      Design:

      Participants will be screened with surveys and a 10-foot walking test. They will have a
      medical history, physical exam, and blood test.

      Participants will be contacted twice in a 1-week period to discuss what they ate over the
      last 24 hours. They will log data about their daily exercise and activities using an online
      fitness tracking app.

      Participants will stay at NIH Clinical Center for 1 week. They will be put into 1 of 2
      groups. One group will follow a ketogenic diet and take MCT oil. The other group will follow
      a low-fat diet. Their body measurements will be taken. They will meet with a physical
      therapist and nutritionist.

      Participants will have daily respiratory and glucose monitoring. They will have cognitive
      tests and complete surveys. They will have walking, motor function, and reaction time/finger
      tapping tests. They will have heart and nerve function tests. They will have
      electrocardiograms and electroencephalograms. Blood will be taken twice daily.

      Participants will follow the ketogenic diet at home for 2 weeks. They will log their
      activities using the fitness tracking app. Then they will have a follow-up visit at NIH.

      Participation in the trial will last for 4 weeks.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        In order to be eligible to participate in this study, an individual must meet all of the
        following criteria:

          1. Must be able to speak English

          2. Able and willing to provide informed consent

          3. Male or female older than age 50 years

          4. Clinically probable diagnosis of Parkinson s Disease by UK Brain Bank Criteria, of
             moderate severity, with ability to safely walk independently for at least a short
             distance (20 feet) as determined on screening visit

          5. BMI > 18.5, to minimize potential risk from expected mild weight loss from ketogenic
             diet

          6. eGFR > 60 by MDRD equation (established on screening visit serum chemistry)

          7. MOCA > 20, as well as having in the investigators' assessment the ability and
             willingness to adhere to either of the study diets

          8. Agreement to adhere to Lifestyle Considerations throughout study duration

          9. Adhering to Usual Diet (SAD) at baseline, as per investigator determination

        EXCLUSION CRITERIA:

        An individual who meets any of the following criteria will be excluded from participation
        in this study:

          1. Atypical Parkinsonism or symptoms suggestive of a diagnosis other than PD by clinical
             criteria

          2. Family history of early onset PD (<age 40) or known personal genetically causal
             etiology of PD (e.g. SNCA duplication, Parkin, PINK, DJ1) by previously obtained
             genetic testing

          3. Currently pregnant

          4. Sarcopenia defined as low BMI (<22 Bahat et al, 2019) with clinically defined weakness

          5. Medical history of cardiac arrhythmia, heart failure, stroke / cerebral hemorrhage,
             epilepsy, other disease of the central nervous system, active cancer, end-stage liver
             disease, advanced kidney disease (CKD stage 3 or ESRD), beta thalassemia, or any other
             medical condition deemed by the PI to pose an increased risk for taking part in the
             study.

          6. Inherited or other metabolic disease known to be worsened by ketogenic diet, e.g.
             inherited defect of lipid or amino acid metabolism

          7. Diabetes on SGLT2 inhibitor or uncontrolled diabetes, defined as Hemoglobin A1c > 8.0%
             on screening test

          8. History of kidney stones or gallbladder surgery

          9. Biliary / liver disease, defined on screening labs, by presence of any of the
             following: Total bilirubin (TB) > 2x ULN or > 2 mg/dL; AST >3x ULN; or ALT >5x ULN

         10. Uncontrolled hypertension, defined as SBP > 180 mmHg or DBP > 105 mmHg on screening
             visit

         11. Hyperlipidemia defined by LDL >/= 160 mg/dL as per ATP-III guidelines

         12. Medical / psychiatric condition identified via clinical assessment in screening visit
             felt to impede completion of the study*

         13. Presence of PD Psychosis or dementia, or other neuropsychiatric or psychiatric illness
             impeding consent and fidelity to the study intervention and/or measurements

         14. Dietary or allergy restrictions as determined by research team to be prohibitive for
             the study

         15. Inability to communicate and provide informed consent in English

         16. No history of previous use of ketogenic or similar diet to a degree that could
             interfere with study blinding

               -  A thorough medical and social history will be performed during the screening
                  visit including questions regarding alcohol and substance abuse. If active
                  alcohol abuse or other current substance abuse is identified which could increase
                  the risk of study participation, then participants will be excluded.