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

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ClinicalTrials.gov Identifier: NCT04584346
Recruitment Status : Completed
First Posted : October 14, 2020
Results First Posted : August 12, 2022
Last Update Posted : September 13, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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.


Condition or disease Intervention/treatment Phase
Parkinson's Disease Dietary Supplement: Liquigen MCT oil Other: Standard American Diet Phase 1

Detailed Description:

Study Description:

While three pilot studies of ketogenic diet (KD) in PD have shown either reduction in motor scores (UPDRS) or improved cognition (memory/fluency), there are gaps in knowledge of the time course and mechanisms of reported outcomes. Furthermore, only a standard ketogenic diet was studied while there are variations such as MCT oil supplementation shown to increase keto-induction, and other adaptations may improve tolerability and micronutrient content. It is the goal of this proposed inpatient metabolic study to address the initial question of effect size and time course of ketosis. If suggestive of benefit in PD, this pilot study may lead to a subsequent larger study of long-term feasibility and effects on disease biomarkers and disease progression, which might also compare alternate diets of interest in PD such as Mediterranean diet. Thus, a pilot feasibility study is proposed, targeting retention rate >80% and adherence in the outpatient setting. Recruitment of 32 participants is based upon power analysis of secondary outcome, testing the Timed Up & Go mobility test that has reported validity in fall prediction, additionally plotting continuous and serially repeated direct/indirect ketosis measurements and motor as well as non-motor symptoms / exploratory disease biomarkers. It is hypothesized that, compared to a non-ketogenic, standard American diet (SAD, also referred to interchangeably as usual diet, ketogenic diet supplemented by MCT oil (MCT-KD) will improve mobility tested by Timed Up & Go (TUG), as well as akinesia, tremor, and memory/executive function tasks, and will reduce motor and non-motor fluctuations within the acute period of keto-induction and early ketogenic timepoints due to improved mitochondrial function and neurotransmitter signaling.

Objectives:

The primary objective is to test the hypothesis that nutritional ketosis (NK) supplemented by MCT oil in a PD cohort (MCT-KD) is feasible for a duration of three weeks. The secondary objective is to show that NK improves PD symptomatology in cognition (improved attention, recall, and executive function), mobility (TUG), and motor function (bradykinesia, akinesia and tremor) within three weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Acute Effects of Medium Chain Triglyceride (MCT) Nutritional Ketosis on Parkinson s Disease (PD) Symptoms and Biomarkers (MCT-PD)
Actual Study Start Date : January 21, 2021
Actual Primary Completion Date : October 13, 2021
Actual Study Completion Date : October 13, 2021


Arm Intervention/treatment
Experimental: Arm A
Ketogenic Diet
Dietary Supplement: Liquigen MCT oil
MCT oil is a nutritional supplement. The Ketogenic diet restricted carbohydrates to reach 80/5-10/10-15 (lipid:carb:protein daily energy) values

Active Comparator: Arm B
Standard American Diet
Other: Standard American Diet
Standard diet with macronutrient composition lipid 35%, protein 10-15%, carbohydrate 50-55%




Primary Outcome Measures :
  1. Feasibiilty of Ketogenic Diet - Retention (Co-primary Endpoint) [ Time Frame: Week 3 ]

    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.


  2. Feasibility of Ketogenic Diet - Adherence (Co-primary Endpoint) [ Time Frame: Week 3 ]

    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.


  3. Feasibility of Ketogenic Diet - Acceptability (Co-primary Endpoint) [ Time Frame: Week 3 ]

    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.



Secondary Outcome Measures :
  1. Timed Up and Go (TUG) [ Time Frame: Day 7 ]
    The Timed Up and Go (TUG) test is a simple test used to assess a person's mobility. The TUG measures the time required to perform a sequence of activities, i.e.,sit-to-stand transfer, straight walking, turning, and walk-to-sit transfer. The TUG is administered at baseline, and each day during the inpatient visit. The results represent a comparison of the group mean score at the end of admission (day 7) for the two cohorts, i.e., patients receiving a Ketogenic Diet and patients receiving a Standard American Diet. A time of greater than 13.5 seconds may suggest a greater risk of falls.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04584346


Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Debra J Ehrlich, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  Study Documents (Full-Text)

Documents provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Additional Information:
Publications:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT04584346    
Other Study ID Numbers: 200153
20-N-0153
First Posted: October 14, 2020    Key Record Dates
Results First Posted: August 12, 2022
Last Update Posted: September 13, 2022
Last Verified: October 13, 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
MCT Medium Chain Triglyceride
Ketogenic Diet
Nutritional Ketosis
Parkinson's Biomarkers
Additional relevant MeSH terms:
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Parkinson Disease
Ketosis
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Acidosis
Acid-Base Imbalance
Metabolic Diseases