Acute Effects of Medium Chain Triglyceride (MCT) Nutritional Ketosis on Parkinson's Disease (PD) Symptoms and Biomarkers (MCT-PD)

NCT04584346 | Completed Phase 1 Results

• 2 other identifiers: 20015320-N-0153
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parkinson's Disease

Keywords

MCT Medium Chain Triglyceride; Ketogenic Diet; Nutritional Ketosis; Parkinson's Biomarkers

Outcome Measures

Primary Outcomes (3)

• Feasibiilty of Ketogenic Diet - Retention (Co-primary Endpoint)

  Analysis of feasibility was determined by 3 co-primary endpoints: retention, adherence, and acceptability, measured at the end of week 3 (outpatient segment). After each co-primary endpoint was calculated, three benchmark criteria were used to determine feasibility. All criteria must be met for feasibility to be positive. Benchmark criteria for Retention was defined as a completion rate at study end (week 3) of \>80%, i.e., \>80% of participants must remain in the study at the 3 week time point.

  Week 3

• Feasibility of Ketogenic Diet - Adherence (Co-primary Endpoint)

  Analysis of feasibility was determined by 3 co-primary endpoints: retention, adherence, and acceptability, measured at the end of week 3 (outpatient segment). After each co-primary endpoint was calculated, three benchmark criteria were used to determine feasibility. All criteria must be met for feasibility to be positive. Benchmark criteria for Adherence was defined as a mean net carbohydrate intake of \</=10% during the 2 week outpatient period. Mean net carbohydrate intake was determined using the following calculation: (total carbohydrates minus total dietary fiber) x 4 divided by total calories.

  Week 3

• Feasibility of Ketogenic Diet - Acceptability (Co-primary Endpoint)

  Analysis of feasibility was determined by 3 co-primary endpoints: retention, adherence, and acceptability, measured at the end of week 3 (outpatient segment). After each co-primary endpoint was calculated, three benchmark criteria were used to determine feasibility. All criteria must be met for feasibility to be positive. Acceptability was defined via an exit survey (at end of study week 3) using a 4-point Likert scale to indicate how likely the participant would continue the diet on at least an intermittent basis in the future with 1 representing "Very likely" and 4 representing "Very unlikely". The benchmark criteria for Acceptability was defined as at least 2 out of 4 on the Likert scale.

  Week 3

Secondary Outcomes (1)

• Timed Up and Go (TUG)

  Day 7

Study Arms (2)

Arm A

EXPERIMENTAL

Ketogenic Diet

Dietary Supplement: Liquigen MCT oil

Arm B

ACTIVE COMPARATOR

Standard American Diet

Other: Standard American Diet

Interventions

Liquigen MCT oil DIETARY_SUPPLEMENT

MCT oil is a nutritional supplement. The Ketogenic diet restricted carbohydrates to reach 80/5-10/10-15 (lipid:carb:protein daily energy) values

Arm A

Standard American Diet OTHER

Standard diet with macronutrient composition lipid 35%, protein 10-15%, carbohydrate 50-55%

Arm B

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Must be able to speak English
• Able and willing to provide informed consent
• Male or female older than age 50 years
• 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
• BMI \> 18.5, to minimize potential risk from expected mild weight loss from ketogenic diet
• eGFR \> 60 by MDRD equation (established on screening visit serum chemistry)
• MOCA \> 20, as well as having in the investigators' assessment the ability and willingness to adhere to either of the study diets
• Agreement to adhere to Lifestyle Considerations throughout study duration
• Adhering to Usual Diet (SAD) at baseline, as per investigator determination

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Atypical Parkinsonism or symptoms suggestive of a diagnosis other than PD by clinical criteria
• 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
• Currently pregnant
• Sarcopenia defined as low BMI (\<22 Bahat et al, 2019) with clinically defined weakness
• 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.
• Inherited or other metabolic disease known to be worsened by ketogenic diet, e.g. inherited defect of lipid or amino acid metabolism
• Diabetes on SGLT2 inhibitor or uncontrolled diabetes, defined as Hemoglobin A1c \> 8.0% on screening test
• History of kidney stones or gallbladder surgery
• 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
• Uncontrolled hypertension, defined as SBP \> 180 mmHg or DBP \> 105 mmHg on screening visit
• Hyperlipidemia defined by LDL \>/= 160 mg/dL as per ATP-III guidelines
• Medical / psychiatric condition identified via clinical assessment in screening visit felt to impede completion of the study\*
• Presence of PD Psychosis or dementia, or other neuropsychiatric or psychiatric illness impeding consent and fidelity to the study intervention and/or measurements
• Dietary or allergy restrictions as determined by research team to be prohibitive for the study

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, Ondo W, Abe K, Macphee G, Macmahon D, Barone P, Rabey M, Forbes A, Breen K, Tluk S, Naidu Y, Olanow W, Williams AJ, Thomas S, Rye D, Tsuboi Y, Hand A, Schapira AH. The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study. Mov Disord. 2007 Oct 15;22(13):1901-11. doi: 10.1002/mds.21596.

  PMID: 17674410 BACKGROUND

• Colla E. Linking the Endoplasmic Reticulum to Parkinson's Disease and Alpha-Synucleinopathy. Front Neurosci. 2019 May 29;13:560. doi: 10.3389/fnins.2019.00560. eCollection 2019.

  PMID: 31191239 BACKGROUND

• Chen MJ, Russo-Neustadt AA. Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent. Hippocampus. 2009 Oct;19(10):962-72. doi: 10.1002/hipo.20579.

  PMID: 19294650 BACKGROUND

• Choi AH, Delgado M, Chen KY, Chung ST, Courville A, Turner SA, Yang S, Airaghi K, Dustin I, McGurrin P, Wu T, Hallett M, Ehrlich DJ. A randomized feasibility trial of medium chain triglyceride-supplemented ketogenic diet in people with Parkinson's disease. BMC Neurol. 2024 Apr 1;24(1):106. doi: 10.1186/s12883-024-03603-5.

  PMID: 38561682 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Dr. Debra Ehrlich
• Organization: National Institutes of Health

debra.ehrlich@nih.gov

301-443-7888

Study Officials

• Debra J Ehrlich, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2020
• First Posted: October 14, 2020
• Study Start: January 21, 2021
• Primary Completion: October 13, 2021
• Study Completion: October 13, 2021
• Last Updated: September 13, 2022
• Results First Posted: August 12, 2022

Record last verified: 2021-10-13

Locations

US (1)