Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Impact of Ketone Bodies and Epigallocatechin Gallate in Multiple Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03740295
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : December 24, 2018
Sponsor:
Collaborator:
Valencian Institute of Neurorehabilitation Foundation
Information provided by (Responsible Party):
José Enrique de la Rubia Ortí, Fundación Universidad Católica de Valencia San Vicente Mártir

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Dietary Supplement: Coconut oil and epigallocatechin gallate Other: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Ketone Bodies and Epigallocatechin Gallate in Multiple Sclerosis
Actual Study Start Date : October 5, 2018
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : February 2019

Resource links provided by the National Library of Medicine


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)




Primary Outcome Measures :
  1. Lipid peroxidation Malondialdehyde (MDA) [ Time Frame: 0-4 months ]
    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.

  2. Tumor necrosis factor alfa (TNF-alpha) [ Time Frame: 0-4 months ]
    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).

  3. Interleukin 6 (IL-6) [ Time Frame: 0-4 months ]
    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).


Secondary Outcome Measures :
  1. Quantitative electroencephalogram (QEEG) [ Time Frame: 0-4 months ]
    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.

  2. Betahydroxybutyrate [ Time Frame: 0-4 months ]

    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.


  3. C-reactive protein [ Time Frame: 0-4 months ]
    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.

  4. Haptoglobin [ Time Frame: 0-4 months ]
    Haptoglobin is an acute phase protein whose expression is a response proportional to inflammation

  5. Field oxide (FOX) [ Time Frame: 0-4 months ]
    The method is based on the principle of the rapid peroxide-mediated oxidation of Fe2+ to Fe3+ under acidic conditions.

  6. Total antioxidants (TEAC) [ Time Frame: 0-4 months ]
    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

  7. Copper reduction capacity (CUPRAC) [ Time Frame: 0-4 months ]
    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.

  8. Iron reduction capacity (FRAP) [ Time Frame: 0-4 months ]
    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.

  9. Paraoxonase 1 (PON1) [ Time Frame: 0-4 months ]
    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.

  10. Anxiety [ Time Frame: 0-4 months ]
    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.

  11. Depression [ Time Frame: 0-4 months ]
    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.

  12. Satiety [ Time Frame: 0-4 months ]
    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.

  13. Sociodemographic [ Time Frame: 0 months ]
    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.

  14. Berg [ Time Frame: 0-4 months ]
    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.

  15. Exercise tolerance [ Time Frame: 0-4 months ]
    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.'"

  16. Gait speed [ Time Frame: 0-4 months ]
    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.

  17. Physical function and symptoms [ Time Frame: 0-4 months ]
    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.

  18. Neurological impairment [ Time Frame: 0-4 months ]
    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.

  19. Manual dexterity [ Time Frame: 0-4 months ]
    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.

  20. Hand Grip Strength [ Time Frame: 0-4 months ]
    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

  21. Muscle power [ Time Frame: 0-4 months ]
    The muscle scale qualifies muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle.

  22. Muscle Strength Assessment Dynamometer (NEDDFM/IBV ) [ Time Frame: 0-4 months ]

    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.


  23. Body diameters [ Time Frame: 0-4 months ]
    Distance taken in projection, between two anatomical points and measured in centimeters (cm), through a pachymeter.

  24. Body perimeters [ Time Frame: 0-4 months ]
    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.

  25. Skinfold calipe [ Time Frame: 0-4 months ]
    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).

  26. Height [ Time Frame: 0-4 months ]
    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

  27. Weight [ Time Frame: 0-4 months ]
    Sum of fat mass and lean mass, expressed in kilograms (kg) and measured by clinical scale.



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.


Layout table for eligibility information
Ages Eligible for Study:   19 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT03740295


Contacts
Layout table for location contacts
Contact: José Enrique De la Rubia Ortí, Farmacy 669 367 704 joseenrique.delarubi@ucv.es

Locations
Layout table for location information
Spain
José Enrique de la Rubia Ortí Recruiting
Valencia, Spain, 46007
Contact: José Enrique De la Rubia Ortí, Farmacy    669 367 704    joseenrique.delarubi@ucv.es   
Sponsors and Collaborators
Fundación Universidad Católica de Valencia San Vicente Mártir
Valencian Institute of Neurorehabilitation Foundation

Layout table for additonal information
Responsible Party: José Enrique de la Rubia Ortí, Director, Fundación Universidad Católica de Valencia San Vicente Mártir
ClinicalTrials.gov Identifier: NCT03740295     History of Changes
Other Study ID Numbers: FundacionUCV
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: December 2018

Layout table for additional information
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

Additional relevant MeSH terms:
Layout table for MeSH terms
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Epigallocatechin gallate
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Neuroprotective Agents