Efficacy of Diet on Quality of Life in Multiple Sclerosis

Study Overview
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Brief Summary
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The overarching goal of this project is to critically evaluate the efficacy of incorporating dietary guidance within multiple sclerosis (MS) care for improving long-term quality of life (QoL) compared to usual care. The primary objective of this study is to evaluate the effect of two dietary interventions (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination) on MS QoL compared to usual care control (Dietary Guidelines for America), and the secondary objectives and the long-term effects on, motor function, low-contrast vision sensitivity, fatigue, mood, and disease activity assessed by brain imaging.

Detailed Description
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In the United States, MS affects nearly 1 million people with a 2.8:1 female to male ratio and the highest incidence rates among whites and African Americans. The economic cost of managing MS is substantial. In the U.S., the total medical costs for patients with MS increased from $116 million in 2002 to $198 million in 2013. MS is a chronic, neuroinflammatory, and neurodegenerative disease-causing symptoms of pain, fatigue, and changes in vision, cognition, and movement that greatly reduce quality of life (QoL) and the ability to maintain employment. The overarching goal of this project is to critically evaluate the efficacy of incorporating dietary guidance within multiple sclerosis (MS) care for improving long-term quality of life (QoL) compared to usual care. The primary objective of this study is to evaluate the effect of two dietary interventions (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination) on MS QoL compared to usual care control (Dietary Guidelines for America), and the secondary objectives and the long-term effects on, motor function, low-contrast vision sensitivity, fatigue, mood, and disease activity assessed by brain imaging. The proposed study will consist of study participants attending 3 in-person site visits, months 0, 3, and 24, and online surveys every 3 months (months 0-24). This study will use a randomized single-blind controlled design to test the short-term (6 months) and long-term (an additional 18 months) impact of the intervention diets on symptoms of MS including QoL and related outcomes stated above. We will use a fourteen-day run-in period to identify participants who are most likely to be successful in completing study procedures; this process has been effective in our previous studies. Participants who successfully complete all baseline self-reported outcomes and follow all study procedures during the seven-day run-in period will be scheduled for an on-site baseline visit for randomization to one of three diets (time restricted olive oil based (TROO) ketogenic and modified Paleolithic elimination and Dietary Guidelines for America). On-site study visits will include blood draws, motor, cognitive, vision function assessments, and MRI. Motor assessments will include a 6-minute walk test, 25-foot walk test, 9-hole pegboard to test hand function, symbol digit exercise to test thinking functions, and critical flicker fusion test, ocular coherence tomography and low contrast vision sensitivity to test vision. The study participant will be escorted to the MRI unit to complete a non-contrast MRI of the brain. At the baseline visit, participants will be randomized. Participants assigned to the intervention diets will be given intervention specific educational materials including shopping lists, example menus and recipes, and the study supplements. Study participants randomized to the dietary guidelines for Americans diet will receive emails and/or text messages (approximately 3-6 weeks) to receive resources with websites for the Dietary Guidelines of America, and recent multiple sclerosis-related research that does not involve diet. Study team will provide fish oil, essential fatty acids, and phosphatidylcholine to the two intervention groups only. The participant will be scheduled for a Zoom video conference meeting with the assigned registered dietitian to review the assigned study diet. In addition, subjects will collect saliva specimens for microbiome analysis at each of the 2 site study visits (month 0 and 24). 24-hour dietary recalls will be collected by a study registered dietitian (RD) (who did not provide training on the respective participants assigned study diet) on three non-consecutive days at baseline, and one per month, at months 10-12, and 22-24. Participants will be given a 3-month window to complete dietary recalls in the event of scheduling conflicts. Participants will be instructed to record key study diet components each day using a study specific questionnaire in the study related (MyCap) application on their smart device. The online questionnaires sent to participants every 2 months will also be used to track supplement intake, medication use, and details about health & life events, MS symptoms, fatigue, quality of life, doctor's appointment, and side effects they may be experiencing.

Official Title
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Efficacy of Diet on Quality of Life in Multiple Sclerosis

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Dietary Supplement: BodyBio Balance Oil
* Dietary Supplement: Kirunal Fish Oil
* Dietary Supplement: BodyBio PC
* Behavioral: Modified Paleolithic Elimination diet
* Behavioral: Time Restricted Olive Oil Based (TROO) Ketogenic Diet
* Behavioral: Usual diet with Dietary Guidelines for Americans Diet information


Participation Criteria
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Eligibility Criteria
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Eligibility for the run-in phase of the study: Participants will be eligible to enroll in the fourteen-day run-in phase of the study if they meet the following inclusion and exclusion criteria: INCLUSION CRITERIA: A definitive diagnosis of RRMS based on the 2017 revised McDonald Criteria. The ability to prepare, or availability of someone to prepare, home-cooked meals. Must own a computer, smartphone, or tablet device that has internet access to complete online surveys and capable of running study related applications. Must be willing to follow study procedures outlined and explained to them. Be between the ages of 18 to 70 at the time of consent. Must be able to walk 25 feet without support. Willingness to be randomized and follow any of the study diets. Must consent to sharing the clinical notes from their primary care and neurology providers during the study period. EXCLUSION CRITERIA: Moderate or severe mental impairment. Use of insulin, Coumadin, weight loss medications such as orlistat that causes fat malabsorption. Worsening of symptoms resulting in the initiation or change of treatment including steroids (solumedrol, prednisone, etc.) or disease-modifying medications in 4 weeks prior to consent. Treatment for cancer by radiation or chemotherapy in 12 months prior to consent, other than skin cancer. Diagnosis of clinically significant heart disease, liver disease, kidney disease, or history of oxalate kidney stones. Diagnosis of type II diabetes that does not have approval from treating physicians to adopt any of the 3 study diets. Clinical diagnosis of moderate to severe psychiatric disease that makes study adherence more difficult (e.g., schizophrenia, bi-polar disease, severe depression and/or anxiety). An active eating disorder such as anorexia, bulimia, binge eating, or orthorexia. Measurement of BMI <20. Confirmation of pregnancy or planning to become pregnant in the next 2 years. History of diagnosed fat intolerance/malabsorption such as cholecystectomy or uncontrolled exocrine pancreatic insufficiency. Participation in another research study investigating MS treatments, diet, or exercise. Presence of a contraindication to completing a brain MRI or having claustrophobia which interferes with completion of MRI studies without the use of sedation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled study design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Modified paleolithic elimination diet).<br>Modified paleolithic elimination diet. | Dietary Supplement: BodyBio Balance Oil<br>* nutraceutical supplement<br>* Other names: 1400 mg linoleic acid/350 mg linolenic acid;Dietary Supplement: Kirunal Fish Oil<br>* nutraceutical supplement<br>* Other names: 315 mg eicosapentanoic acid/ 105 mg docosahexaenoic acid;Dietary Supplement: BodyBio PC<br>* nutraceutical supplement<br>* Other names: 1300 mg phosphatidylcholine;Behavioral: Modified Paleolithic Elimination diet<br>* Complete elimination of all gluten-, dairy-, and egg-containing foods. Increase fruit and vegetable intake to 6-9 servings/day comprising of 2-3 servings each of the following categories: intensely colored, sulfur-rich, and leafy greens. Consume 6-12 ounces/day protein including organ meats and fatty fish. Consume fermented foods daily. Consume daily servings of algae, seaweed, and nutritional yeast.<br>|
| Experimental: Group 2 (TROO)<br>Time Restricted Olive Oil Based (TROO) Ketogenic Diet | Dietary Supplement: BodyBio Balance Oil<br>* nutraceutical supplement<br>* Other names: 1400 mg linoleic acid/350 mg linolenic acid;Dietary Supplement: Kirunal Fish Oil<br>* nutraceutical supplement<br>* Other names: 315 mg eicosapentanoic acid/ 105 mg docosahexaenoic acid;Dietary Supplement: BodyBio PC<br>* nutraceutical supplement<br>* Other names: 1300 mg phosphatidylcholine;Behavioral: Time Restricted Olive Oil Based (TROO) Ketogenic Diet<br>* Restriction of dietary carbohydrates to < 50 grams/day. Use olive oil (cold-pressed extra virgin preferred) to increase fat intake to >160 grams/day. Consume <100 grams/day protein. Limit dairy to 2 servings/day of whole fat options (completely exclude reduced fat dairy). Consume at least 3 servings/day non-starchy vegetables.<br>|
| Active Comparator: Group 3 Control<br>Usual diet with Dietary Guidelines for Americans Diet information | Behavioral: Usual diet with Dietary Guidelines for Americans Diet information<br>* Limit sodium to < 2,300 mg/day. Limit added sugar and saturated fat intake to <10% of kcal/day, respectively. Consume 5 servings of fruits and vegetables per day. Consume 6-9 ounce equivalents/day of grains, making at least half whole grain options. Consume 3 servings of reduced fat dairy per day. Consume 6 ounces/day protein foods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH) | Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better. | baseline to 3 Months | 
| Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH) | Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better. | baseline to 6 Months | 
| Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH) | Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better. | baseline to 12 Months | 
| Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH) | Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better. | baseline to 18 Months | 
| Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH) | Change in (MS 54 QoL MH) survey questions mean scores, range 0-100, higher number is better. | baseline to 24 Months | 
| Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH) | Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better. | baseline to 3 Months | 
| Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH) | Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better. | baseline to 6 Months | 
| Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH) | Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better. | baseline to 12 Months | 
| Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH) | Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better. | baseline to 18 Months | 
| Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH) | Change in (MS 54 QoL PH) survey questions mean scores, range 0-100, higher number is better. | baseline to 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Fatigue Impact Scale (MFIS) | Change in MFIS survey questions, scores range from 0-84, lower score is better. | baseline to 3 months | 
| Modified Fatigue Impact Scale (MFIS) | Change in MFIS survey questions, scores range from 0-84, lower score is better. | baseline to 6 months | 
| Modified Fatigue Impact Scale (MFIS) | Change in MFIS survey questions, scores range from 0-84, lower score is better. | baseline to 12 months | 
| Modified Fatigue Impact Scale (MFIS) | Change in MFIS survey questions, scores range from 0-84, lower score is better. | baseline to 18 months | 
| Modified Fatigue Impact Scale (MFIS) | Change in MFIS survey questions, scores range from 0-84, lower score is better. | baseline to 24 months | 
| Hospital Anxiety Depression Scale (HADS) | Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence | baseline to 3 months | 
| Hospital Anxiety Depression Scale (HADS) | Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence | baseline to 6 months | 
| Hospital Anxiety Depression Scale (HADS) | Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence | baseline to 12 months | 
| Hospital Anxiety Depression Scale (HADS) | Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence | baseline to 18 months | 
| Hospital Anxiety Depression Scale (HADS) | Change in HADS survey question score, a 14 question scale ranging from 0-3 with zero being being low or no occurrence and 3 being high occurrence | baseline to 24 months | 
| Fatigue Severity Scale score (FSS) | Change in FSS survey question mean scores, scores range from 1-7, lower is better. | Baseline to 3 months | 
| Fatigue Severity Scale score (FSS) | Change in FSS survey question mean scores, scores range from 1-7, lower is better. | Baseline to 6 months | 
| Fatigue Severity Scale score (FSS) | Change in FSS survey question mean scores, scores range from 1-7, lower is better. | Baseline to 12 months | 
| Fatigue Severity Scale score (FSS) | Change in FSS survey question mean scores, scores range from 1-7, lower is better. | Baseline to 18 months | 
| Fatigue Severity Scale score (FSS) | Change in FSS survey question mean scores, scores range from 1-7, lower is better. | Baseline to 24 months | 
| Brain volume as measured by non contrast magnetic resonance imaging (MRI) | Change in MRI grey matter brain volume, more is better | baseline to 24 months | 
| Brain lesions as measured by non contrast magnetic resonance imaging (MRI) | Change in inflammatory lesions numbers as measured by non contrast brain MRI, fewer is better | baseline to 24 months | 
| Timed 25 foot walk test | seconds required to walk 25 feet, lower is better | baseline to 3 months | 
| Timed 25 foot walk test | seconds required to walk 25 feet, lower is better | baseline to 24 months | 
| 9 Hole peg board test | seconds require to move 9 pegs to various locations on a peg board, fewer seconds is better | baseline to 3 months | 
| 9 Hole peg board test | seconds require to move 9 pegs to various locations on a peg board, fewer seconds is better | baseline to 24 months | 
| Low contrast visual acuity | A measure of best corrected vision, measure is log minimal angle of resolution at 2.5% contrast. Lower number is better. | baseline to 3 months | 
| Low contrast visual acuity | A measure of best corrected vision, measure is log minimal angle of resolution at 2.5% contrast. Lower number is better. | baseline to 24 months | 
| 24 hour dietary intake recalls | Change in dietary intake measured by dietary interview conducted via telephone call; more nutrients meeting recommended dietary allowance is better. | baseline to 12 months | 
| 24 hour dietary intake recalls | Change in dietary intake measured by dietary interview conducted via telephone call; more nutrients meeting recommended dietary allowance is better. | baseline to 24 months | 
| Critical flicker fusion | The herz at which a flickering light is seen as non-flickering as measured by herz | baseline to 3 months | 
| Critical flicker fusion | The herz at which a flickering light is seen as non-flickering as measured by herz | baseline to 24 months | 
| Ocular Coherence tomography | Measure of optic nerve and retina depths using infrared light technology | baseline | 
| Neurofilament light chain | blood biomarker of neuroaxonal (brain) damage | baseline to 3 months | 
| Neurofilament light chain | blood biomarker of neuroaxonal (brain) damage | baseline to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary, nutrition, fatigue, quality of life