Efficacy of Early Harvest Olive Oil in Cognition of Primary (PPMS) or Secondary (SPMS) Progressive Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT04120675
• Recruitment Status: Recruiting
• First Posted: October 9, 2019
• Last Update Posted: October 9, 2019
• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: Greek Alzheimer's Association and Related Disorders; YANNI'S OLIVE GROVE
• Information provided by (Responsible Party): Magda Tsolaki, Aristotle University Of Thessaloniki

Study Description

Brief Summary:

To date, no drug therapy has been approved for primary (PPMS) & secondary (SPMS) progressive multiple sclerosis. The urgent need to find new therapies - if possible with minimal side effects - led us to the search for the potential therapeutic effects of early harvest olive oil. The positive effect of phenol-rich, flavonoid and lignin-based olive oil on the modification of intestinal microbe populations and their by-products of metabolism is well known, such as the extent of gut-associated lymphoid tissue immune-stimulation due to antioxidants, anti-inflammatory and immunoregulatory properties. The aim of this Greek, Randomized, Double Blind, Controlled Prospective Study, is to evaluate the effect of freshly-pressed extra virgin olive oil in the progression of the cognition in patients diagnosed with PPMS or SPMS. Specific inflammatory markers in blood, stool and CSF will be detected to confirm the general, beneficial effect of freshly pressed EVOO on the gut microbiota, the metabolomic profile and the immune system of patients, as their cross-interaction has been shown in many clinical studies. Positive results of this mild,nutritional, therapeutic intervention can also lead to the clinical use of these biomarkers for both diagnosis and follow up of the patients.

Condition or disease	Intervention/treatment	Phase
Progressive Multiple Sclerosis	Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil	Not Applicable

Detailed Description:

Study Type: Interventional Study Design: Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention OBJECTIVES OF THE TRIAL The objectives of this study are:To investigate the efficacy of freshly pressed EVOO as a disease course modifying treatment for primary (PPMS) or secondary (SPMS) progressive multiple sclerosis in a phase III double-blind -controlled study in objective measurements in patients with primary (PPMS) or secondary (SPMS) progressive multiple sclerosis.

STUDY DESIGN This is a Greek, randomized, double-blind, -controlled study group of Freshly-Pressed EVOO + MeDi compared to EVOO + MeDi and to Medi only. Qualifying patients will be randomly assigned to receive 50mL of freshly-pressed EVOO or extra virgin olive oil or MeDi dietary protocol on a daily basis for 24 months. Patients undergo assessments at baseline,12 and 24 months +/- 7 days after beginning treatment.

Duration: The total study duration will be 30 months. Patients will receive study interventions for 24 months.

Number of Subjects 150 subjects total will be enrolled; 50 in the experimental group (freshly pressed EVOO+MeDi); 50 in the Control Group 1(extra virgin olive oil+MeDi) and 50 in control Group 2(same dietary habits-MeDi protocol).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double (Participant and neuropsychologist)
• Primary Purpose: Prevention
• Official Title: Randomized, Double Blind, Controlled Prospective Study, to Evaluate the Therapeutic Effects of Early Harvest Olive Oil in Cognitive Functions of Patients With Primary (PPMS) or Secondary (SPMS) Progressive Multiple Sclerosis.
• Actual Study Start Date: November 9, 2018
• Estimated Primary Completion Date: February 15, 2020
• Estimated Study Completion Date: May 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: 3 Arms and Interventions; Experimental Group 50 patients on Freshly-Pressed Extra Virgin Olive Oil Aluminum bottle with 500 ml of freshly-pressed extra virgin olive oil 1 bottle per 10 days. Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil dietary intake of the content of 50 mL (3 tablespoons from the bottle containing the product)	Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil; This is a Greek, randomized, double-blind, -controlled study group of Freshly-Pressed EVOO + MeDi compared to EVOO + MeDi and to Medi only. Qualifying patients will be randomly assigned to receive 50mL of freshly-pressed EVOO or extra virgin olive oil or MeDi dietary protocol on a daily basis for 24 months. Patients undergo assessments at baseline,12 and 24 months +/- 7 days after beginning treatment.
Active Comparator: Control group 1; 50 patients on Extra Virgin Olive Oil Aluminum bottle with 500 ml of freshly-pressed extra virgin olive oil 1 bottle per 10 days. Extra Virgin Olive Oil dietary intake of the content of 50 mL (3 tablespoons from the bottle containing the product)	Dietary Supplement: Freshly-Pressed Extra Virgin Olive Oil; This is a Greek, randomized, double-blind, -controlled study group of Freshly-Pressed EVOO + MeDi compared to EVOO + MeDi and to Medi only. Qualifying patients will be randomly assigned to receive 50mL of freshly-pressed EVOO or extra virgin olive oil or MeDi dietary protocol on a daily basis for 24 months. Patients undergo assessments at baseline,12 and 24 months +/- 7 days after beginning treatment.
No Intervention: Control Group 2; 50 patients will have the same dietary habits and a MeDi protocol

Outcome Measures

Primary Outcome Measures :

1. Neuropsychological Assessment - Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
   Changes in Mini-Mental State Examination (MMSE) score
2. FUCAS-Measurements to Assess Daily Functionality [ Time Frame: baseline, 12 and 24 months ]
   Changes in Functional cognitive assessment scale (FUCAS) score
3. Letter & Category Fluency Test- Measurement to Assess Verbal Fluency and Learning [ Time Frame: baseline, 12 and 24 months ]
   Changes in the Letter & Category Fluency Test
4. CDR- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
   Changes in Global Clinical Dementia Rating (CDR) score (sum of boxes
5. MoCA- Measurements to Assess General Cognitive Function [ Time Frame: Time Frame: baseline, 12 and 24 months ]
   Changes in Montreal Cognitive Assessment (MoCA)
6. CANTAB- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
   Changes in Cambridge Neuropsychological Test Automated Battery (CANTAB)
7. Clock Drawing test- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
   Changes in the Clock Drawing test
8. Logical Memory test- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
   Changes in the Logical Memory test
9. Digit Span Forward & Backward test- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
   Changes in the Digit Span Forward & Backward test
10. WAIS-R Digit Symbol- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
    Changes in the WAIS-R Digit Symbol Substitution Test
11. TMT part A and B- Measurements to Assess General Cognitive Function [ Time Frame: baseline, 12 and 24 months ]
    Changes in the Trail Making Test
12. ADASCog-Measurements to Assess Daily Functionality [ Time Frame: baseline, 12 and 24 months ]
    Changes in Alzheimer's Disease Assessment Scale-Cognitive (ADASCog)
13. Functional Rating Scale for Dementia-Measurements to Assess Daily Functionality [ Time Frame: baseline, 12 and 24 months ]
    Changes in Functional Rating Scale for Dementia (FRSSD)
14. Auditory Verbal Learning Test- Measurement to Assess Verbal Fluency and Learning [ Time Frame: baseline, 12 and 24 months ]
    Changes in the Auditory Verbal Learning Test
15. Boston Naming Test- Measurement to Assess Verbal Fluency and Learning [ Time Frame: baseline, 12 and 24 months ]
    Changes in the Boston Naming Test

Secondary Outcome Measures :

1. NeuroImaging [ Time Frame: baseline, 12 and 24 months ]
   Changes in brain Magnetic Resonance Imaging (MRI) 1.5 Tesla (brain atrophy)
2. CSF - beta amyloid [ Time Frame: baseline, 12 and 24 months ]
   Changes in mean values on high sensitivity beta-amyloid 1-42 protein
3. CSF TAU-protein [ Time Frame: baseline, 12 and 24 months ]
   Changes in mean values on TAU-protein in cerebrospinal fluid
4. Neurophysiology and ERPs [ Time Frame: Time Frame: baseline, 12 and 24 months ]
   •Changes in Event-Related Potential (ERP) (oddball paradigm, auditory ERPs)
5. Electroencephalography recording [ Time Frame: Time Frame: baseline, 12 and 24 months ]
   •Changes in Electroencephalography (EEG), resting state.The device records brain signals through 57 electrodes, 2 reference electrodes attached to the earlobes, and a ground electrode placed at a left anterior position

Other Outcome Measures:

1. Weight in Kilograms [ Time Frame: baseline, 12 and 24 months ]
   Changes in weight
2. Height in Meters [ Time Frame: baseline, 12 and 24 months ]
   Changes in Height

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Confirmed diagnosis of primary (PPMS) or secondary (SPMS) progressive multiple sclerosis
• EDSS≥ 5
• No response to any given treatment for MS or interruption due to side effects
• Progressive aggravation in the disease's progression estimated by: deterioration in EDSS-plus disability scale, Timed 25-Foot Walk or 9-hole peg test.
• Progressive aggravation in the disease's progression estimated by: new lesions in MRI scan and neuropsychological tests
• Progressive aggravation in patient's neuropsychological status
• Progressive aggravation in patient's Quality of life, estimated with MuSIQol - Greek 3.01 MS and SF-36
• Years of education: >= 5
• Proficient language fluency
• Have a study partner with 10+ hr/wk contact (can be in person and telephone), accompanies to visits
• Compliance

Exclusion Criteria:

• Enrollment in other trials or studies not compatible with MSOIL
• Visual and auditory acuity inadequate for neuropsychological testing
• History of significant other neurological or psychiatric illnesses or presence of other diseases precluding enrollment.
• Use of forbidden medications (listed below)
• Ferromagnetic implants and devices (including implants or devices held in place by sutures, granulation or ingrowth of tissue, fixation devices, or by other means) not eligible for MRI scanning. Brain malformation or other conditions that may complicate lumbar puncture
• Any significant or uncontrolled medical condition or treatment-emergent
• Clinically significant laboratory abnormality

Medications across the study

Excluded Medication:

• Immunosuppressant or immunomodulating agents, corticosteroids, or investigational drugs within 3 months of study initiation
• Antibiotics in general, at least one month prior assessment of specific inflammatory markers (faecal levels of calprotectin, metabolomic profile, gut microbiota)
• Use of neuroleptics or within 4 weeks of screening
• Participation in any other investigational drug study within 4 weeks of screening (individuals may not participate in any drug study while participating in this protocol).

Contacts and Locations

Contacts

Contact: Magda Tsolaki, MD,PhD,Professor; 0030 2310 2411 56; tsolakim1@gmail.com

Contact: THOMAS CHATZINTOUNAS, MD,PhD; tomchatzidounas@gmail.com

Locations

Greece

A' Department of Neurology,Aristotle University of Thessaloniki (AUTH); Recruiting

Thessaloniki, Macedonia, Greece, 546 36

Contact: Magda Tsolaki, MD, PhD, Professor 0030 2310 2411 56 tsolakim1@gmail.com

Principal Investigator: Magda Tsolaki, MD, PhD, Professor

Sub-Investigator: Thomas Chatzintounas, MD, PhD,Neurologist

Sponsors and Collaborators

Aristotle University Of Thessaloniki

Greek Alzheimer's Association and Related Disorders

YANNI'S OLIVE GROVE

More Information

• Responsible Party: Magda Tsolaki, MD, PhD, Professor, Aristotle University Of Thessaloniki
• ClinicalTrials.gov Identifier: NCT04120675
• Other Study ID Numbers: 43-Α/24-10-2018
• First Posted: October 9, 2019
• Last Update Posted: October 9, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Magda Tsolaki, Aristotle University Of Thessaloniki:

extra virgin olive oil; primary (PPMS) progressive multiple sclerosis; secondary (SPMS) progressive multiple sclerosis; randomized double blind clinical trial; cognition

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases