Impact of Ketone Bodies and Epigallocatechin Gallate in Multiple Sclerosis

Based on the fact that the fundamental pathogenic mechanism of the Multiple Sclerosis (MS) disease is neuroinflammation, related in turn to cellular oxidation and mitochondrial alterations, this project aims to assess the impact of a nutritional intervention on the evolution of MS patients in their different slopes. To this end, the administration of medium-chain triglycerides, whose metabolism produces the increase of ketone bodies in the blood, will be carried out; and another of the antioxidant polyphenol epigallocatechin gallate. This procedure will be applied over 6 months, based on a isocaloric Mediterranean diet, with a population for the study of 80 patients with different variants of the disease. The assessment of the intervention will be carried out every two months, at motor-functional, anthropometric, cognitive and emotional, inflammatory, and oxidation levels.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Placebo; Dietary supplement: Coconut oil and epigallocatechin gallate

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46007
    • José Enrique de la Rubia Ortí

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multiple Sclerosis patients older than 19 years ans under 65 who sign informed consent of the study

Exclusion Criteria:

• Patients with coconut oil intolerance or other chronic metabolic pathologies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Multiple Sclerosis	Other: Placebo; Lactose
Experimental: Intervention Multiple Sclerosis	Dietary supplement: Coconut oil and epigallocatechin gallate; 600 mg of epigallocatechin gallate (EGCG) and 60 ml of coconut oil (3600 mg of TGCM) per day, divided into two doses (one in the morning and one at noon)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid peroxidation Malondialdehyde (MDA)	Malondialdehyde (MDA) will be used as perioxidation marker. It is based on the reaction of thiobarbituric with malondialdehyde, product of the splitting of hydroperoxides, thus forming a color that can be measured directly. Its analysis is used for its good practicability and simplicity, but it lacks sensitivity, so it is recommended, to increase it, to use fluorometric or chromatographic procedures.	0-4 months
Tumor necrosis factor alfa (TNF-alpha)	Plasma concentrations of inflammatory markers (IL-6 and TNF-a) were determined by using a multiplex ELISA (Human ProInflammatory II 4-Plex Ultra-Sensitive Kit; Meso Scale Diagnostics).	0-4 months
Interleukin 6 (IL-6)	Plasma concentrations of inflammatory markers (IL-6 and TNF-a) were determined by using a multiplex ELISA (Human ProInflammatory II 4-Plex Ultra-Sensitive Kit; Meso Scale Diagnostics).	0-4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative electroencephalogram (QEEG)	A QEEG brain map (or 'Q' for short) enables us to see your unique pattern of mental strengths and weaknesses - areas of the brain where there is too little or too much activity, and areas that are not coordinating their activity the best they could.	0-4 months
Betahydroxybutyrate	Beta-hydroxybutyrate (BHB) inhibits the NLRP3 gene, which is part of a complex set of proteins called the inflammasome. The inflammasome drives the inflammatory response in several diseases, among which are some autoimmune diseases.	0-4 months
C-reactive protein	C-reactive protein (CRP) is produced by the liver. The level of CRP rises when there is inflammation throughout the body. This is one of a group of proteins called "acute phase reactants" that increase in response to inflammation.	0-4 months
Haptoglobin	Haptoglobin is an acute phase protein whose expression is a response proportional to inflammation	0-4 months
Field oxide (FOX)	The method is based on the principle of the rapid peroxide-mediated oxidation of Fe2+ to Fe3+ under acidic conditions.	0-4 months
Total antioxidants (TEAC)	TEAC is a spectrophotometric technique that is based on inhibition from the antioxidants of the absorbance of the radical cation of 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) (2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate), a stable blue-green chromophore that has a characteristic long wavelength absorption spectrum	0-4 months
Copper reduction capacity (CUPRAC)	CUPRAC method based on the reduction of Cu (II) in hydroetanolic medium (pH 7.0) in the presence of neocuproin (2,9-dimethyl-1,10-phenanthroline), by polyphenols resulting in complexes of Cu.	0-4 months
Iron reduction capacity (FRAP)	The FRAP assay, is presented as a novel method for assessing ''antioxidant power.'' Ferric to ferrous ion reduction at low pH causes a colored ferrous-tripyridyltriazine complex to form.	0-4 months
Paraoxonase 1 (PON1)	The enzyme Paraoxonase 1 (PON-1), is synthesized in the liver and is attached to the apolipoprotein A1 of high density lipoprotein (HDL). PON1 is able to hydrolyze organophosphates compounds (e.g. paraoxon, diazoxon, soman, sarin), has arylesterase and lactonase function by hydrolyzing lactones, homocysteine thiolactone specifically to regenerate homocysteine.	0-4 months
Anxiety	The State-Trait Anxiety Inventory (STAI). This is a self-report measure of immediate and general anxiety. A patient is shown or read aloud a statement (e.g. 'I feel jittery') and is required to indicate to what degree, from a choice of four frequencies, the statement relates to them. Range score for each subtest is 20-80, the higher score indicating greater anxiety. A cut point of 39-40 has been suggested to detect clinically significant symptoms for the State Anxiety.	0-4 months
Depression	Beck Depression Inventory (BDI). This is a self-report measure of depression. A patient is shown or read aloud groups of four statements, which range from a normal thought to a profoundly depressed thought. The patient must indicate which of the four is closest to how they have been feeling over the past week. The range score is 0-63, the higher score indicating greater depression.	0-4 months
Satiety	Perceptions of hunger, desire to eat and satiation were performed by VAS, which provides an accurate way to predict appetite in young adults and has good reproducibility. VAS, 100mm in lenght with words anchored at each end, expressing the most positive and the most negative rating, were used to assess hunger, satiety, fullness, prospective food consumptions best represented their sensation at the time. The volunteers were instructed to make a point at the point where best represented their sensation at the time.	0-4 months
Sociodemographic	The demographic characteristics (age, gender, etc.) and clinical characteristics (year of diagnosis, type of multiple sclerosis, etc.) of the sample were measured through an ad hoc sociodemographic questionnaire.	0 months
Berg	This scale rates performance from 0 (cannot perform) to 4 (normal performance) on 14 items with a maximum total score of 56.18,19 The validity and reliability of the scale have been assessed on populations of subjects with multiple sclerosis.	0-4 months
Exercise tolerance	The Two-minute walk test (2MWT) is a short version of an exercise tolerance test and reports the distance in meters during a 2-minute walk. The objective of the test is to walk as far as possible for 2 minutes. Participants, remembering the objective, walked at a comfortable speed between 2 cones that were 20m apart. If they had to turn, they moved the unaffected side. They were permitted to slow down, stop, and rest as necessary during the 2-minute walk. The time was started when participants started walking and proceeded until 2 minutes elapsed, even if they slowed down or stopped walking. The instructions were, "Go. Keep walking until I say 'stop' or until you are too tired, and stop when I say 'stop.'"	0-4 months
Gait speed	The 10-meter walk test is a simple, effective and widely used tool to evaluate gait speed. The 6MWT evaluates endurance by measuring the maximum distance an individual can walk within 6 min, and determines the walking capacity.	0-4 months
Physical function and symptoms	Disabilities of the arm, shoulder and hand (DASH) 30 items, self-report rating scale will be used to measure physical functions and symptoms' in people with disorders of the upper limb. Items are scored from 1 (no difficulty) to 5 (unable). A total 'disability/symptom' score is generated by summing items, and averaging to produce a mean item score between 1 and 5. This value is then transformed to a score out of 100 by subtracting one and multiplying by 25. A higher score indicates greater disability.	0-4 months
Neurological impairment	Kurtzke's Expanded Disability Status Scale (EDSS) is the most widely used measure which attempts to capture the full extent of MS symptoms in a standardised way. It was selected for this study because of its universal currency. Both the EDSS and Functional Systems were recorded. The EDSS provides a total score on scale that ramges from 0 to 10. The higher degrees means more disability.	0-4 months
Manual dexterity	It was measured with the Nine Hole Peg Test (NHPT). The time needed to place and remove 9 pegs was recorded and averaged over 2 trials. Manual dexterity speed was calculated as pegs per second and used in the analyses. Participants who were not able to place any peg within a time limit of 300 seconds received a score of 0 pegs per second.	0-4 months
Hand Grip Strength	The instrument used was a Jamar handgrip dynamometer. The dynamometer has a dial meter. Its handle was positioned in the second notch. In that position the grip width was approximately 4.0 cm	0-4 months
Muscle power	The muscle scale qualifies muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle.	0-4 months
Muscle Strength Assessment Dynamometer (NEDDFM/IBV )	This allows the determination of the degree of muscular weakness of the large muscular groups of lower and upper limb in the different planes of movement. The system assists the evaluator, providing, in real time, the force exerted by a certain muscle group, the maximum effort reached during the exercise and the corresponding deficiency according to the scales of RD 1971/1999 or the AMA disability assessment tables. The results of the assessment can be displayed on the screen and printed on a report card.	0-4 months
Body diameters	Distance taken in projection, between two anatomical points and measured in centimeters (cm), through a pachymeter.	0-4 months
Body perimeters	They are indicators of body fat and protein reserves, so they are useful to know the nutritional status. Perimeters from the thorax, waist, arm, forearm and thigh, will be measure in centimeters (cm), through a tape measure.	0-4 months
Skinfold calipe	This method is based on the measurement of the thickness of the subcutaneous adipose tissue in precisely defined and protocolized places, measured with a pleximeter and taking into account the guidelines of the ISAK (The International Society for Advancement of Kinanthropometry).	0-4 months
Height	It is expressed in centimeters (cm), measuring the distance between the vertex and the plane of support of the individual by means of a stadiometer and placing the head on the Frankfort plane	0-4 months
Weight	Sum of fat mass and lean mass, expressed in kilograms (kg) and measured by clinical scale.	0-4 months

Collaborators and Investigators

• Sponsor: Fundación Universidad Católica de Valencia San Vicente Mártir
• Collaborators: Valencian Institute of Neurorehabilitation Foundation

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2018
• Primary Completion (Actual): January 5, 2019
• Study Completion (Actual): February 5, 2019

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Neuroprotective Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Antimutagenic Agents; Epigallocatechin gallate
• Other Study ID Numbers: FundacionUCV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No