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

Primary Purpose

Parkinson's Disease

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Liquigen MCT oil

Standard American Diet

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring MCT Medium Chain Triglyceride, Ketogenic Diet, Nutritional Ketosis, Parkinson's Biomarkers

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

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

EXCLUSION CRITERIA:

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
Inability to communicate and provide informed consent in English
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.

Sites / Locations

National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

Ketogenic Diet

Standard American Diet

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Timed Up and Go (TUG)

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.

Full Information

NCT ID

NCT04584346

First Posted

October 10, 2020

Last Updated

August 17, 2022

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT04584346

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 13, 2021

Overall Recruitment Status

Completed

Study Start Date

January 21, 2021 (Actual)

Primary Completion Date

October 13, 2021 (Actual)

Study Completion Date

October 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

Ketogenic Diet

Arm Title

Arm B

Arm Type

Active Comparator

Arm Description

Standard American Diet

Intervention Type

Dietary Supplement

Intervention Name(s)

Liquigen MCT oil

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

Intervention Type

Other

Intervention Name(s)

Standard American Diet

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Week 3

Title

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

Description

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.

Time Frame

Week 3

Title

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

Description

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.

Time Frame

Week 3

Secondary Outcome Measure Information:

Title

Timed Up and Go (TUG)

Description

Time Frame

Day 7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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 Inability to communicate and provide informed consent in English 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Debra J Ehrlich, M.D.

Organizational Affiliation

National Institute of Neurological Disorders and Stroke (NINDS)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17674410

Citation

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.

Results Reference

background

PubMed Identifier

31191239

Citation

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.

Results Reference

background

PubMed Identifier

19294650

Citation

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.

Results Reference

background

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2020-N-0153.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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