Functional Outcomes From Diets in Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to test the effects of two dietary interventions, glycemic load and calorie restriction, on physical function, cognition, pain, fatigue, mood, and anxiety in adults with multiple sclerosis (MS). The investigators will also explore the how the diet interventions impact inflammation, immunity, and metabolic biomarkers.

Detailed Description
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100 participants will be randomized 1:1 to follow either a low glycemic load (GL) or standard GL diet for 32 weeks. For the first 16 weeks, all participants will eat enough calories to maintain their baseline weight. During the second 16 weeks, all participants will reduce calorie intake by 500kcal/day, with a goal of losing 5-10% of initial body weight. Participants will complete data collection at baseline (prior to randomization), at 17 weeks (after the weight stable phase) and again after completing the calorie restriction phase. All participants will receive meal plans and groceries for the duration of the trial.

Official Title
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The Impact of Diet Quality and Calorie Restriction on Physical Function and Patient Reported Outcomes in Multiple Sclerosis

Conditions
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Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis

Intervention / Treatment
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* Behavioral: Glycemic load
* Behavioral: Calorie restriction
* Behavioral: Behavioral support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with RRMS or SPMS BMI 25-50 kg/m2 (overweight/obese) EDSS ≤6.5 (able to walk 100m with or without assistance) If on disease-modifying treatment (DMT), stable for 6 months If not on DMT, no DMT in previous 6 months No expected change to DMT in next 34 weeks Responsible for food preparation or have input into food preparation Exclusion Criteria: MS relapse in previous 30 days Unable to walk 25 feet with or without assistive device Pregnant or breastfeeding Current use of insulin or sulfonylurea agents Score indicating low cognitive functioning on the Telephone Interview for Cognitive Status (TICS-m) assessment Actively engaged in a weight loss program or unwilling to follow assigned dietary pattern Unable to receive, store, or prepare food according to diet plan Medical contraindication to either treatment or control diet (including severe allergies that cannot be accommodated within either group)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to follow either a low GL or standard GL diet for 32 weeks. For the first 16 weeks, both groups will eat enough calories to maintain baseline weight. During the second 16 weeks, both groups will reduce calorie intake by 500 kcal/day,
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Glycemic Load<br>This group will be prescribed a daily GL of <45 points/1000 kcal and 25% of daily calorie intake from carbohydrates. This group will be provided few processed foods. During the first 16 weeks, this group will eat enough calories to maintain baseline weight, and will reduce daily calorie intake by 500 kcal/day in the second 16 weeks. | Behavioral: Glycemic load<br>* Participants will be provided food to meet GL prescription for the duration of the trial.<br>Behavioral: Calorie restriction<br>* Participants will be provided food to meet their prescribed daily calorie intake for the duration of the trial (weight stable in first 16 weeks, weight loss in second 16 weeks).<br>Behavioral: Behavioral support<br>* All participants will receive behavioral supports in the form of email, text, information pages and weekly calls from the study staff to maximize adherence.<br>|
| Active Comparator: Standard Glycemic Load<br>This group will be prescribed a daily GL of >75 points/1000kcal and 60% of daily calorie intake from carbohydrates. This group will be provided more processed foods than the low GL group. During the first 16 weeks, this group will eat enough calories to maintain baseline weight, and will reduce daily calorie intake by 500 kcal/day in the second 16 weeks. | Behavioral: Glycemic load<br>* Participants will be provided food to meet GL prescription for the duration of the trial.<br>Behavioral: Calorie restriction<br>* Participants will be provided food to meet their prescribed daily calorie intake for the duration of the trial (weight stable in first 16 weeks, weight loss in second 16 weeks).<br>Behavioral: Behavioral support<br>* All participants will receive behavioral supports in the form of email, text, information pages and weekly calls from the study staff to maximize adherence.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis Functional Composite (MSFC) | The MSFC includes a timed T25FW, 9-hole peg test (9HPT), and the Paced Auditory Serial Addition Test (PASAT). | Baseline | 
| Multiple Sclerosis Functional Composite (MSFC) | The MSFC includes a timed T25FW, 9-hole peg test (9HPT), and the Paced Auditory Serial Addition Test (PASAT). | 17 weeks | 
| Multiple Sclerosis Functional Composite (MSFC) | The MSFC includes a timed T25FW, 9-hole peg test (9HPT), and the Paced Auditory Serial Addition Test (PASAT). | 34 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief International Cognitive Assessment for MS (BICAMS) | The BICAMS includes the Single Digit Modalities Test, California Verbal Learning Test, and Brief Visuospatial Memory Test | Baseline | 
| Brief International Cognitive Assessment for MS (BICAMS) | The BICAMS includes the Single Digit Modalities Test, California Verbal Learning Test, and Brief Visuospatial Memory Test | 17 weeks | 
| Brief International Cognitive Assessment for MS (BICAMS) | The BICAMS includes the Single Digit Modalities Test, California Verbal Learning Test, and Brief Visuospatial Memory Test | 34 weeks | 
| Patient reported outcomes: Hospital Anxiety and Depression Scale (HADS) | The HADS contains 14 items that measure the frequency of anxiety and depressive symptoms over the past week. The anxiety questions are scaled 0-3 with 0 representing higher anxiety to 3 representing no anxiety. The depression questions are scaled from 0 indicating no depression to 3 indicating more signs of depression. | Baseline | 
| Patient reported outcomes: Hospital Anxiety and Depression Scale (HADS) | The HADS contains 14 items that measure the frequency of anxiety and depressive symptoms over the past week. The anxiety questions are scaled 0-3 with 0 representing higher anxiety to 3 representing no anxiety. The depression questions are scaled from 0 indicating no depression to 3 indicating more signs of depression. | 17 weeks | 
| Patient reported outcomes: Hospital Anxiety and Depression Scale (HADS) | The HADS contains 14 items that measure the frequency of anxiety and depressive symptoms over the past week. The anxiety questions are scaled 0-3 with 0 representing higher anxiety to 3 representing no anxiety. The depression questions are scaled from 0 indicating no depression to 3 indicating more signs of depression. | 34 Weeks | 
| Patient reported outcomes: Modified Fatigue Impact Scale (MFIS) | The MFIS is a 21-item measure of physical, cognitive, and psychosocial impact of fatigue on daily life over the past 4 weeks. The scale ranges from 0 to 4 with 0 being never have issues regarding fatigue to 4 representing fatigue greatly affecting the participants life. | Baseline | 
| Patient reported outcomes: Modified Fatigue Impact Scale (MFIS) | The MFIS is a 21-item measure of physical, cognitive, and psychosocial impact of fatigue on daily life over the past 4 weeks. The scale ranges from 0 to 4 with 0 being never have issues regarding fatigue to 4 representing fatigue greatly affecting the participants life. | 17 weeks | 
| Patient reported outcomes: Modified Fatigue Impact Scale (MFIS) | The MFIS is a 21-item measure of physical, cognitive, and psychosocial impact of fatigue on daily life over the past 4 weeks. The scale ranges from 0 to 4 with 0 being never have issues regarding fatigue to 4 representing fatigue greatly affecting the participants life. | 34 Weeks | 
| Patient reported outcomes: Fatigue Severity Scale (FSS) | The FSS is a 9-item unidimensional measure of fatigue and its disabling consequences over the past week in medical populations including MS. The score is from 1 to 7 with 1 representing strongly disagreeing that fatigue has an impact on them to 7 representing strongly agreeing fatigue has an impact on the participants. | Baseline | 
| Patient reported outcomes: Fatigue Severity Scale (FSS) | The FSS is a 9-item unidimensional measure of fatigue and its disabling consequences over the past week in medical populations including MS. The score is from 1 to 7 with 1 representing strongly disagreeing that fatigue has an impact on them to 7 representing strongly agreeing fatigue has an impact on the participants. | 17 weeks | 
| Patient reported outcomes: Fatigue Severity Scale (FSS) | The FSS is a 9-item unidimensional measure of fatigue and its disabling consequences over the past week in medical populations including MS. The score is from 1 to 7 with 1 representing strongly disagreeing that fatigue has an impact on them to 7 representing strongly agreeing fatigue has an impact on the participants. | 34 Weeks | 
| Patient reported outcomes: Visual Analog Fatigue Scale (VAFS) | The participants will be asked to rate their global fatigue on a scale of 0-10 with 0 being the worst fatigued and 10 being normal. | Baseline | 
| Patient reported outcomes: Visual Analog Fatigue Scale (VAFS) | The participants will be asked to rate their global fatigue on a scale of 0-10 with 0 being the worst fatigued and 10 being normal. | 17 weeks | 
| Patient reported outcomes: Visual Analog Fatigue Scale (VAFS) | The participants will be asked to rate their global fatigue on a scale of 0-10 with 0 being the worst fatigued and 10 being normal. | 34 Weeks | 
| Patient reported outcomes: Short-form McGill Pain Questionnaire Revised (SF-MPQ-2) | The SF-MPQ has a 15-item adjective checklist that captures sensory and affective dimensions of pain experienced over the past week. Questions are scored from 0-10. Zero representing no pain and 10 representing the highest pain level. | Baseline | 
| Patient reported outcomes: Short-form McGill Pain Questionnaire Revised (SF-MPQ-2) | The SF-MPQ has a 15-item adjective checklist that captures sensory and affective dimensions of pain experienced over the past week. Questions are scored from 0-10. Zero representing no pain and 10 representing the highest pain level. | 17 weeks | 
| Patient reported outcomes: Short-form McGill Pain Questionnaire Revised (SF-MPQ-2) | The SF-MPQ has a 15-item adjective checklist that captures sensory and affective dimensions of pain experienced over the past week. Questions are scored from 0-10. Zero representing no pain and 10 representing the highest pain level. | 34 Weeks | 
| Patient reported outcomes: Pittsburg Sleep Quality Index (PSQI) | The questionnaire has fill in the blank questions along with questions that are rated on a scale. The scale rating is not during the past month to three or more times per week. | Baseline | 
| Patient reported outcomes: Pittsburg Sleep Quality Index (PSQI) | The questionnaire has fill in the blank questions along with questions that are rated on a scale. The scale rating is not during the past month to three or more times per week. | 17 weeks | 
| Patient reported outcomes: Pittsburg Sleep Quality Index (PSQI) | The questionnaire has fill in the blank questions along with questions that are rated on a scale. The scale rating is not during the past month to three or more times per week. | 34 Weeks |