Clinical trial NCT05007483: Efficacy of Diet on Quality of Life in Multiple Sclerosis
Official title: Efficacy of Diet on Quality of Life in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: dietary
nutrition
fatigue
quality of life
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2021-08-16
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled study design
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)
timeFrame: baseline to 3 Months
measure: Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)
timeFrame: baseline to 6 Months
measure: Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)
timeFrame: baseline to 12 Months
measure: Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)
timeFrame: baseline to 18 Months
measure: Multiple Sclerosis 54 Quality of Life Mental Health (MS 54 QoL MH)
timeFrame: baseline to 24 Months
measure: Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)
timeFrame: baseline to 3 Months
measure: Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)
timeFrame: baseline to 6 Months
measure: Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)
timeFrame: baseline to 12 Months
measure: Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)
timeFrame: baseline to 18 Months
measure: Multiple Sclerosis 54 Quality of Life Physical Health (MS 54 QoL PH)
timeFrame: baseline to 24 Months
Secondary outcomes:
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: baseline to 3 months
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: baseline to 6 months
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: baseline to 12 months
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: baseline to 18 months
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: baseline to 24 months
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: baseline to 3 months
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: baseline to 6 months
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: baseline to 12 months
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: baseline to 18 months
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: baseline to 24 months
measure: Fatigue Severity Scale score (FSS)
timeFrame: Baseline to 3 months
measure: Fatigue Severity Scale score (FSS)
timeFrame: Baseline to 6 months
measure: Fatigue Severity Scale score (FSS)
timeFrame: Baseline to 12 months
measure: Fatigue Severity Scale score (FSS)
timeFrame: Baseline to 18 months
measure: Fatigue Severity Scale score (FSS)
timeFrame: Baseline to 24 months
measure: Brain volume as measured by non contrast magnetic resonance imaging (MRI)
timeFrame: baseline to 24 months
measure: Brain lesions as measured by non contrast magnetic resonance imaging (MRI)
timeFrame: baseline to 24 months
measure: Timed 25 foot walk test
timeFrame: baseline to 3 months
measure: Timed 25 foot walk test
timeFrame: baseline to 24 months
measure: 9 Hole peg board test
timeFrame: baseline to 3 months
measure: 9 Hole peg board test
timeFrame: baseline to 24 months
measure: Low contrast visual acuity
timeFrame: baseline to 3 months
measure: Low contrast visual acuity
timeFrame: baseline to 24 months
measure: 24 hour dietary intake recalls
timeFrame: baseline to 12 months
measure: 24 hour dietary intake recalls
timeFrame: baseline to 24 months
measure: Critical flicker fusion
timeFrame: baseline to 3 months
measure: Critical flicker fusion
timeFrame: baseline to 24 months
measure: Ocular Coherence tomography
timeFrame: baseline
measure: Neurofilament light chain
timeFrame: baseline to 3 months
measure: Neurofilament light chain
timeFrame: baseline to 24 months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Univeristy of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Terry L Wahls, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wahls TL, Chenard CA, Snetselaar LG. Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic. Nutrients. 2019 Feb 7;11(2):352. doi: 10.3390/nu11020352.
citation: Wahls T, Scott MO, Alshare Z, Rubenstein L, Darling W, Carr L, Smith K, Chenard CA, LaRocca N, Snetselaar L. Dietary approaches to treat MS-related fatigue: comparing the modified Paleolithic (Wahls Elimination) and low saturated fat (Swank) diets on perceived fatigue in persons with relapsing-remitting multiple sclerosis: study protocol for a randomized controlled trial. Trials. 2018 Jun 4;19(1):309. doi: 10.1186/s13063-018-2680-x.
citation: Chenard CA, Rubenstein LM, Snetselaar LG, Wahls TL. Nutrient Composition Comparison between a Modified Paleolithic Diet for Multiple Sclerosis and the Recommended Healthy U.S.-Style Eating Pattern. Nutrients. 2019 Mar 1;11(3):537. doi: 10.3390/nu11030537.
citation: Titcomb TJ, Bisht B, Moore DD 3rd, Chhonker YS, Murry DJ, Snetselaar LG, Wahls TL. Eating Pattern and Nutritional Risks among People with Multiple Sclerosis Following a Modified Paleolithic Diet. Nutrients. 2020 Jun 20;12(6):1844. doi: 10.3390/nu12061844.
citation: Lee JE, Bisht B, Hall MJ, Rubenstein LM, Louison R, Klein DT, Wahls TL. A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis. J Am Coll Nutr. 2017 Mar-Apr;36(3):150-168. doi: 10.1080/07315724.2016.1255160. Epub 2017 Apr 10.
citation: Lee JE, Titcomb TJ, Bisht B, Rubenstein LM, Louison R, Wahls TL. A Modified MCT-Based Ketogenic Diet Increases Plasma beta-Hydroxybutyrate but Has Less Effect on Fatigue and Quality of Life in People with Multiple Sclerosis Compared to a Modified Paleolithic Diet: A Waitlist-Controlled, Randomized Pilot Study. J Am Coll Nutr. 2021 Jan;40(1):13-25. doi: 10.1080/07315724.2020.1734988. Epub 2020 Mar 26.
citation: Chenard CA, Rubenstein LM, Snetselaar LG, Wahls TL. Nutrient Composition Comparison between the Low Saturated Fat Swank Diet for Multiple Sclerosis and Healthy U.S.-Style Eating Pattern. Nutrients. 2019 Mar 13;11(3):616. doi: 10.3390/nu11030616.
citation: Irish AK, Erickson CM, Wahls TL, Snetselaar LG, Darling WG. Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2017 Jan 4;7:1-18. doi: 10.2147/DNND.S116949. eCollection 2017.
citation: Bisht B, Darling WG, Grossmann RE, Shivapour ET, Lutgendorf SK, Snetselaar LG, Hall MJ, Zimmerman MB, Wahls TL. A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med. 2014 May;20(5):347-55. doi: 10.1089/acm.2013.0188. Epub 2014 Jan 29.