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This is a pragmatic, single-blinded randomized trial of improving adherence to dietary interventions in patients with MS who are receiving monthly natalizumab infusions.
MS affects at least 400,000 people in the US alone, and its incidence has increased in the past 50 years, likely due to changing environmental risk factors. Recent research suggests that diet may be a critical factor in the development of MS. The "Western diet", high in sugar, fat, and salt, may influence MS risk and progression by directly affecting the immune system, altering gut bacteria, and changing metabolism.
Studying patients with MS who are overweight and obese may be relevant as obesity can cause chronic low-grade inflammation, potentially worsening MS symptoms. Diet modification represents an interesting potential therapy for MS, particularly calorie restriction and fasting, which have been associated with reduced markers of inflammation. In addition to these direct effects, weight optimization may lead to improvements in MS-related symptoms, like fatigue, and overall quality of life.
This is a single-blinded randomized trial of adherence to a dietary intervention in patients with MS who are receiving monthly natalizumab infusions. The study will evaluate how use of technology may help patients with MS adhere to a calorie restricted diet. It will also evaluate the effect of weight loss on fatigue and quality of life in patients with MS. A second part of the study will evaluate if shortening the period during the day in which people consume their typical food amounts leads to improvements in patient-reported outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Calorie Restriction - Frequent Patient Communication | Experimental | MS patients receiving monthly natalizumab infusions will use the LoseIt! smartphone application to log daily food consumption. Data from the app will be collected at follow-up visits. Patients will receive initial training in using the app, and then receive weekly supportive messages encouraging them to adhere to the calorie restriction diet between 3- and 6-month followup visits. Results will be compared primarily to those collected from the Standard of Care arm. |
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| Timing Restriction | Experimental | MS patients receiving monthly natalizumab infusions who are ineligible for the calorie restriction portion of the study (the Frequent Patient Activation and Standard of Care arms) will be offered the option to enroll in the second part of the study, assessing differences in outcomes between daily 16-hour fasting periods and no dietary changes. Patients in the second part of the study randomized to this arm will consume their normal daily food intake, but restrict eating to an 8-hour period during the day. Results will be compared to patients who do not make any changes to their diet, the No Change arm. |
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| Calorie Restriction - Communication Standard of Care | Placebo Comparator | MS patients receiving monthly natalizumab infusions will use the LoseIt! smartphone application to log daily food consumption. Data from the app will be collected at follow-up visits. Besides initial training with the application and 3- and 6-month follow up exams, participants will not receive additional support or interaction from the study team.Results will be compared with those collected from the Frequent Patient Interaction arm. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Frequent Patient Interaction | Other | Weekly informational and supportive text messages will be sent to patients, encouraging adherence to the calorie restriction diet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Adherence | Number of participants adhering to the prescribed dietary intervention at the end of the 6-month study period. | Baseline and 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Body Mass Index (BMI) | Change in body mass index from baseline to 6 months. | Baseline and 6 months |
| Weight Change | Change in participant weight over the 6-month study period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ellen Mowry, MD | Johns Hopkins University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32408153 | Derived | Roman SN, Fitzgerald KC, Beier M, Mowry EM. Safety and feasibility of various fasting-mimicking diets among people with multiple sclerosis. Mult Scler Relat Disord. 2020 Jul;42:102149. doi: 10.1016/j.msard.2020.102149. Epub 2020 May 6. |
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Individual participant's data will not be shared
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| ID | Title | Description |
|---|---|---|
| FG000 | Calorie Restriction - Frequent Patient Communication | MS patients receiving monthly natalizumab infusions will use the LoseIt! smartphone application to log daily food consumption. Data from the app will be collected at follow-up visits. Patients will receive initial training in using the app, and then receive weekly supportive messages encouraging them to adhere to the calorie restriction diet between 3- and 6-month followup visits. Results will be compared primarily to those collected from the Standard of Care arm. Frequent Patient Interaction: Weekly informational and supportive text messages will be sent to patients, encouraging adherence to the calorie restriction diet. LoseIt! Smartphone Application: Patients will be trained by study staff to download the LoseIt! application, and use it to log all food intake throughout the study duration. Data collected from the application will be the primary measure of adherence to dietary changes. |
| FG001 | Calorie Restriction - Communication Standard of Care | MS patients receiving monthly natalizumab infusions will use the LoseIt! smartphone application to log daily food consumption. Data from the app will be collected at follow-up visits. Besides initial training with the application and 3- and 6-month follow up exams, participants will not receive additional support or interaction from the study team.Results will be compared with those collected from the Frequent Patient Interaction arm. LoseIt! Smartphone Application: Patients will be trained by study staff to download the LoseIt! application, and use it to log all food intake throughout the study duration. Data collected from the application will be the primary measure of adherence to dietary changes. |
| FG002 | Timing Restriction | MS patients receiving monthly natalizumab infusions who are ineligible for the calorie restriction portion of the study (the Frequent Patient Activation and Standard of Care arms) will be offered the option to enroll in the second part of the study, assessing differences in outcomes between daily 16-hour fasting periods and no dietary changes. Patients in the second part of the study randomized to this arm will consume their normal daily food intake, but restrict eating to an 8-hour period during the day. Results will be compared to patients who do not make any changes to their diet, the No Change arm. Timing Restriction: Patients continue to follow their normal diet, but limit food intake to an 8-hour period during the day. |
| FG003 | No Diet Change | MS patients receiving natalizumab infusions who were ineligible for the calorie restriction portion of the study (e.g. body mass index < 25 kg/m^2) or did not wish to participate in calorie restriction, may elect to be part of the second portion of the study. If so, they may be randomized to this arm, in which no changes are made to amount or timing of daily food intake. Results will be compared with the experimental Timing arm |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Calorie Restriction - Frequent Patient Communication | Participants select to restrict calories continuously (25% daily) or intermittently (76% twice per week) for the 6-month study period. Weekly informational and supportive text messages will be sent to patients, encouraging adherence to the calorie restriction diet. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Adherence | Number of participants adhering to the prescribed dietary intervention at the end of the 6-month study period. | Posted | Count of Participants | Participants | Baseline and 6 months |
|
Adverse event data was collected through the duration of the 6-month intervention period for each participant. Including all participants, this data was collected from October 2016 until the end of June 2017.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Calorie Restriction - Frequent Patient Communication | Participants select to restrict calories continuously (25% daily) or intermittently (76% twice per week) for the 6-month study period. Weekly informational and supportive text messages will be sent to patients, encouraging adherence to the calorie restriction diet. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Migraine | Nervous system disorders | Non-systematic Assessment | One patient with a known history of migraine headaches experienced migraines on fasting days for the intermittent calorie restriction option, and self-discontinued the dietary intervention. |
Limited sample size; Participants were enrolled from one treatment center, limited to patients with relapsing-remitting subtype of MS on natalizumab treatments; Calorie and timing data were self-reported by participants.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ellen Mowry, M.D., M.C.R. | Johns Hopkins Department of Neurology | 410-502-0675 | emowry1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 20, 2016 | Apr 9, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D015431 | Weight Loss |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| No Diet Change | No Intervention | MS patients receiving natalizumab infusions who were ineligible for the calorie restriction portion of the study (e.g. body mass index < 25 kg/m^2) or did not wish to participate in calorie restriction, may elect to be part of the second portion of the study. If so, they may be randomized to this arm, in which no changes are made to amount or timing of daily food intake. Results will be compared with the experimental Timing arm |
| Timing Restriction | Behavioral | Patients continue to follow their normal diet, but limit food intake to an 8-hour period during the day. |
|
| LoseIt! Smartphone Application | Device | Patients will be trained by study staff to download the LoseIt! application, and use it to log all food intake throughout the study duration. Data collected from the application will be the primary measure of adherence to dietary changes. |
|
| Baseline and 6 months |
| Weight Change Among Adherent Participants | The change in weight over 6 months among participants were remained adherence to the calorie restriction diet versus those who admitted to non-compliance by the end of the study period. | Baseline and 6 months |
| Functional Assessment in MS Score | The Functional Assessment in Multiple Sclerosis (FAMS) is an instrument that measures quality of life among people with MS. The instrument contains 44 questions scored on a 5-point Likert scale in 6 areas: mobility, symptoms, emotional wellbeing, general contentment, thanking/fatigue, and family/social wellbeing. Subscores for each area is calculated as the sum of responses in that section, and the total FAMS score is the sum of all subscores. Minimum total score is 0 and maximum total score is 176, where a higher score indicates better quality of life. Increase in the FAMS score over the study period indicates a better outcome, or improved quality of life, among participants. | Baseline and 6 months |
| Fatigue | The Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue is a question bank of 95 items validated to evaluated fatigue in a variety of chronic conditions. The PROMIS-FatigueMS is a subset of 8 questions from the question bank, which have been validated to measure fatigue in people with multiple sclerosis. Individual items are scored on a 5-point Likert scale, and the total score is the sum of individual items, with a minimum score of 8 and maximum score of 40. Lower scores indicate less fatigue, while higher scores indicate more fatigue. Reduction in score over 6 months indicates a better outcome, or improved fatigue among participants. | Baseline and 6 months |
| Sleep Quality | The Pittsburgh Sleep Quality Index (PSQI) is an instrument used to measure the quality and sleeping pattern of adults. It differentiates "poor" from "good" sleep quality, and the total score is calculated from the sum of seven components, each scored from 0 to 3. The minimum total score is 0 and the maximum total score is 21. A total score equal to or greater than 5 units indicates "poor" quality sleep, while a score of 0-4 indicates "good" quality sleep; lower scores indicate better sleep quality. Decrease in PSQI score indicates a better outcome, or improved sleep quality, among study participants. | Baseline and 6 months |
| Self-esteem | The Rosenberg Self-Esteem Scale (RSES) is a 10-item scale that measures global self-worth using a 4-point Likert scale to ask about negative and positive feelings about the self. Individual items are summed to calculate the total score. Minimum score is 0 and maximum score is 30. Scores between 15 and 25 are considered within the normal range, while scores below 15 indicates poor self-esteem. An increase in RSES score over 6 months indicates a better outcome, or improved self-esteem, among participants. | Baseline and 6 months |
| Withdrawal by Subject |
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| Lost to Follow-up |
|
| Calorie Restriction - Communication Standard of Care |
Participants select to restrict calories continuously (25% daily) or intermittently (76% twice per week) for the 6-month study period. Participants will not receive additional support or interaction from the study team apart from the scheduled study visits. |
| BG002 | Timing Restriction | Patients who do not qualify for, or do not wish to complete, the calorie restriction diet, may be randomized to time restriction. In this arm, participants restrict their calorie intake to an 8-hour interval each day, providing time for a 16-hour fast between intervals. |
| BG003 | No Diet Change | Patients who do not qualify for, or do not wish to complete, the calorie restriction diet, may be randomized to not make any diet changes. This group is instructed to continue eating their normal diet throughout the 6-month study period. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Waist Circumference | Mean | Standard Deviation | cm |
|
| Hip Circumference | Mean | Standard Deviation | cm |
|
| Patient-Determined Disability Score | The Patient-Determine Disability Scale (PDDS) measures level of disability from multiple sclerosis as reported by the patient. The scale ranges from a minimum of 0 (No disability - "I may have some mild symptoms, mostly sensory due to MS, but they do not limit my activity") to a maximum of 8 (Bedridden - "Unable to sit in a wheelchair for more than one hour"). Lower values on this scale indicate less disability from multiple sclerosis. A reduction in PDDS over the study period indicates a better outcome, or improvement in disability/symptoms from MS, among participants. | Mean | Standard Deviation | scores on a scale |
|
| Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue-MS Score | The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue is a 95-item question bank to evaluate fatigue in a variety of chronic conditions. The PROMIS-FatigueMS is a subset of 8 questions from the question bank, which have been validated to measure fatigue specifically in people with multiple sclerosis. Individual items are scored on a 5-point Likert scale, and the total score is the sum of individual items, with a minimum score of 8 and maximum score of 40. Lower scores indicate less fatigue; reduction in score over 6 months indicates a better outcome. | Mean | Standard Deviation | scores on a scale |
|
| Pittsburgh Sleep Quality Index Score | The Pittsburgh Sleep Quality Index (PSQI) is an instrument used to measure the quality and sleeping pattern of adults. It differentiates "poor" from "good" sleep quality, and the total score is calculated from the sum of seven components, each scored from 0 to 3. The minimum total score is 0 and the maximum total score is 21. A total score equal to or greater than 5 units indicates "poor" quality sleep, while a score of 0-4 indicates "good" quality sleep; lower scores indicate better sleep quality. | Mean | Standard Deviation | scores on a scale |
|
| Quality of Life | The Functional Assessment in Multiple Sclerosis (FAMS) is an instrument that measures quality of life among people with MS. It contains 44 questions scored on a 5-point Likert scale in 6 areas: mobility, symptoms, emotional wellbeing, general contentment, thinking/fatigue, and family/social wellbeing. Subscores are the sum of responses in that section, and the total FAMS score is the sum of all subscores. Minimum total score is 0 and maximum total score is 176, where a higher score indicates better quality of life. Increase in score over the study period indicates a better outcome. | Mean | Standard Deviation | scores on a scale |
|
| Rosenberg Self-Esteem Score | The Rosenberg Self-Esteem Scale (RSES) is a 10-item scale that measures global self-worth using a 4-point Likert scale to ask about negative and positive feelings about the self. Individual items are summed to calculate the total score. Minimum score is 0 and maximum score is 30. Higher scores indicate higher/better self-esteem. Scores between 15 and 25 are considered within the normal range, while scores below 15 indicates poor self-esteem. An increase in RSES score over 6 months indicates a better outcome, or improved self-esteem, among participants. | Mean | Standard Deviation | scores on a scale |
|
| OG002 | Timing Restriction | Patients who do not qualify for, or do not wish to complete, the calorie restriction diet, may be randomized to time restriction. In this arm, participants restrict their calorie intake to an 8-hour interval each day, providing time for a 16-hour fast between intervals. |
| OG003 | No Diet Change | Patients who do not qualify for, or do not wish to complete, the calorie restriction diet, may be randomized to not make any diet changes. This group is instructed to continue eating their normal diet throughout the 6-month study period. |
|
|
| Secondary | Body Mass Index (BMI) | Change in body mass index from baseline to 6 months. | 5 out of the initial 43 participants dropped out of the study voluntarily | Posted | Mean | Standard Deviation | kg/m^2 | Baseline and 6 months |
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| Secondary | Weight Change | Change in participant weight over the 6-month study period | 5 out of the initial 43 participants dropped out of the study voluntarily | Posted | Mean | Standard Deviation | KG | Baseline and 6 months |
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| Secondary | Weight Change Among Adherent Participants | The change in weight over 6 months among participants were remained adherence to the calorie restriction diet versus those who admitted to non-compliance by the end of the study period. | Discrepancy in numbers is due to non-completers. 5 out of the initial 43 participants dropped out of the study voluntarily | Posted | Mean | Standard Deviation | kg | Baseline and 6 months |
|
|
|
| Secondary | Functional Assessment in MS Score | The Functional Assessment in Multiple Sclerosis (FAMS) is an instrument that measures quality of life among people with MS. The instrument contains 44 questions scored on a 5-point Likert scale in 6 areas: mobility, symptoms, emotional wellbeing, general contentment, thanking/fatigue, and family/social wellbeing. Subscores for each area is calculated as the sum of responses in that section, and the total FAMS score is the sum of all subscores. Minimum total score is 0 and maximum total score is 176, where a higher score indicates better quality of life. Increase in the FAMS score over the study period indicates a better outcome, or improved quality of life, among participants. | 5 out of the initial 43 participants dropped out of the study voluntarily | Posted | Mean | Standard Deviation | scores on a scale | Baseline and 6 months |
|
|
|
| Secondary | Fatigue | The Patient-Reported Outcomes Measurement Information System (PROMIS) - Fatigue is a question bank of 95 items validated to evaluated fatigue in a variety of chronic conditions. The PROMIS-FatigueMS is a subset of 8 questions from the question bank, which have been validated to measure fatigue in people with multiple sclerosis. Individual items are scored on a 5-point Likert scale, and the total score is the sum of individual items, with a minimum score of 8 and maximum score of 40. Lower scores indicate less fatigue, while higher scores indicate more fatigue. Reduction in score over 6 months indicates a better outcome, or improved fatigue among participants. | Discrepancy in numbers is due to non-completers | Posted | Mean | Standard Deviation | scores on a scale | Baseline and 6 months |
|
|
|
| Secondary | Sleep Quality | The Pittsburgh Sleep Quality Index (PSQI) is an instrument used to measure the quality and sleeping pattern of adults. It differentiates "poor" from "good" sleep quality, and the total score is calculated from the sum of seven components, each scored from 0 to 3. The minimum total score is 0 and the maximum total score is 21. A total score equal to or greater than 5 units indicates "poor" quality sleep, while a score of 0-4 indicates "good" quality sleep; lower scores indicate better sleep quality. Decrease in PSQI score indicates a better outcome, or improved sleep quality, among study participants. | 5 out of the initial 43 participants dropped out of the study voluntarily | Posted | Mean | Standard Deviation | scores on a scale | Baseline and 6 months |
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| Secondary | Self-esteem | The Rosenberg Self-Esteem Scale (RSES) is a 10-item scale that measures global self-worth using a 4-point Likert scale to ask about negative and positive feelings about the self. Individual items are summed to calculate the total score. Minimum score is 0 and maximum score is 30. Scores between 15 and 25 are considered within the normal range, while scores below 15 indicates poor self-esteem. An increase in RSES score over 6 months indicates a better outcome, or improved self-esteem, among participants. | 5 out of the initial 43 participants dropped out of the study voluntarily | Posted | Mean | Standard Deviation | scores on a scale | Baseline and 6 months |
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|
| 0 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
| EG001 | Calorie Restriction - Communication Standard of Care | Participants select to restrict calories continuously (25% daily) or intermittently (76% twice per week) for the 6-month study period. Participants will not receive additional support or interaction from the study team apart from the scheduled study visits. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG002 | Timing Restriction | Patients who do not qualify for, or do not wish to complete, the calorie restriction diet, may be randomized to time restriction. In this arm, participants restrict their calorie intake to an 8-hour interval each day, providing time for a 16-hour fast between intervals. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG003 | No Diet Change | Patients who do not qualify for, or do not wish to complete, the calorie restriction diet, may be randomized to not make any diet changes. This group is instructed to continue eating their normal diet throughout the 6-month study period. | 0 | 12 | 0 | 12 | 0 | 12 |
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |