A Pragmatic Trial of Dietary Programs in People With Multiple Sclerosis
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: Johns Hopkins University

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
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A pragmatic trial of dietary program in people with multiple sclerosis 
NCT02846558 
Document Date:  7/20/16

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 2 of 13 
 
JHM IRB - eForm A – Protocol 
 
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1. 
Abstract 
a. Provide no more than a one page research abstract briefly stating the problem, the 
research hypothesis, and the importance of the research. 
Background: The increase in multiple sclerosis (MS) incidence over the last 50 years is likely 
caused by environmental factors. 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. 
While vitamin D insufficiency, cigarette smoking, and Epstein-Barr virus play a role, they do not 
account for the entirety of the increase. Recent research suggests that diet may be a critical factor 
in MS risk and prognosis; the increasingly common “Western diet”, high in sugar, fat, and salt, 
may influence MS risk and progression by directly modulating the immune system, altering gut 
bacteria, and changing metabolism.  
 
Furthermore, co-morbidity related to overweight and obesity may be relevant to MS, as obesity 
results in chronic low-grade inflammation, may contribute to the initiation of neuroinflammatory 
processes, and appears to be associated with poorer disease outcomes in people with MS. Dietary 
modification represents an intriguing potential MS intervention, particularly calorie restriction and 
fasting, which have been associated with reduced pro-inflammatory cytokines, ceramides, and 
markers of oxidative stress. Beyond these direct biological effects, optimization of weight may 
lead to improvements in MS-related symptoms such as fatigue and in overall health-related quality 
of life. As a result, there is a strong rationale for evaluating the benefits of calorie restriction in MS 
patients as well as strategies to optimize adherence in a real-world setting. Since there are also 
some data to suggest that restricting calorie intake to a shortened period within the 24-hour day 
may also be of benefit, we will also evaluate, in those who don’t meet criteria for the calorie 
restriction protocol or who refuse to participate in it, whether consolidating typical food intake into 
a shorter period within each 24-hour day leads to improvements in biomarkers of metabolic 
impairment or in patient-reported outcomes. 
 
Purpose: The first part of our study will evaluate whether minimal support through weekly 
automated messaging helps people with MS adhere to a calorie restricted diet. It will also evaluate 
the effect of weight loss, particularly abdominal obesity, on fatigue and health-related quality of 
life in patients with MS. The second program will evaluate if shortening the period during the day 
in which people consume their typical food amounts leads to improvements in patient-reported 
outcomes or markers of metabolism.  
 
Hypotheses: Intermittent reminders about the importance of adhering to a dietary intervention 
combined with use of a calorie-tracking smartphone application will improve adherence over use 
of the application alone. Weight loss, especially decreased abdominal obesity, will improve fatigue 
and quality of life in patients with MS. Even in people who are not reducing their calorie intake, 
consuming those calories within a shorter time period within each 24 hours will improve metabolic 
markers and patient-reported outcomes. 
 
2. 
Objectives (include all primary and secondary objectives) 
 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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Primary Objective. To evaluate if automated messaging support helps people with MS adhere 
to calorie restriction diet. We predict that intermittent reminders about the importance of adhering 
to a dietary intervention combined with use of a calorie-tracking smartphone application that is 
intermittently shared with the study team, will lead to better adherence than use of the application 
alone in overweight and obese people with MS. 
 
 
Secondary Objectives.  A) To assess the effect of weight loss, particularly reduced abdominal 
obesity, on fatigue, health-related quality of life, and self-esteem in overweight and obese 
people with MS. Based on the current literature, we hypothesize that weight loss will improve these 
aspects of patient well-being. 
 
B) To assess if shortening the time period in which typical calories are consumed during the 
day improves markers of metabolism, fatigue, or health-related quality of life in people with 
MS. We hypothesize that consolidating calories consumed into a shorter period of the day leads to 
improvements in metabolism and patient-reported outcomes. 
 
 
 
1. 
Background  
 
The increase in multiple sclerosis (MS) incidence is likely caused by environmental factors. MS 
affects at least 400,000 people in the US alone, and its incidence has increased in the past 50 
years,1 likely due to changing environmental risk factors. While vitamin D insufficiency, cigarette 
smoking, and Epstein-Barr virus play a role,2 they do not account for the entirety of the increase, 
supporting a search for other relevant factors. Since environmental factors are more readily 
modifiable than are genetic factors, there is a crucial need to identify them so that interventions can 
be made to reduce the consequences of this disabling disease.  
 
Inflammation and neurodegeneration influence MS phenotype. While most patients have relapsing 
MS at onset, about 10% have progressive-onset MS, and 50% of those whose disease begins with 
relapses convert to a progressive phenotype. While relapses are thought to be due to demyelinating 
autoimmune attacks, neurodegeneration likely causes progressive MS.3,4 The link between relapses 
and progression may be explained by inflammation-induced mitochondrial dysfunction that leads 
to neurotoxicity via increased reactive oxygen species and calcium.5 
 
Diet may be a critical factor in MS risk and prognosis. Somewhat in parallel with the increased MS 
incidence, dietary intake has changed markedly in recent years, with an increased consumption of 
the “Western” diet, characterized by a high amount of sugar, fat, and salt. Diet may influence MS 
in several ways, including directly modulating the immune system, altering gut bacteria, or 
changing metabolism (including modifying oxidative stress or mitochondrial function). The role of 
diet is interesting in light of recent data suggesting childhood obesity is also a risk factor for 
multiple sclerosis as well as an additional report suggesting a genetic overlap between MS and 
cardiometabolic factors.6,7 
 
Co-morbidity related to overweight/obesity may be relevant to MS. Obesity results in chronic low-
grade inflammation and may contribute to the initiation of neuroinflammatory processes in MS, 
possibly through increases in blood-brain barrier permeability or proinflammatory cytokine 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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release. In addition, obesity-related disorders are also common in MS patients,8 and co-morbidity 
in people with MS appears to be associated with poorer disease outcomes.9,10  
 
Dietary modification represents an intriguing potential MS intervention. One aspect of diet that 
shows promise involves calorie intake. Calorie restriction or fasting prior to the induction of 
experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, is associated with a 
less aggressive course.11,12 There may be several mechanisms by which this occurs. Calorie 
restriction and fasting are associated with reductions in pro-inflammatory cytokines and 
other inflammatory markers in EAE mice 11,12and in humans who are healthy, obese, or have 
asthma, similar reductions have been observed.13-16 Ceramides are elevated in MS patients and 
pathogenic in vitro;17 calorie restriction reduces their levels in humans without MS.15 Calorie 
restriction also reduces markers of oxidative stress,15 and thus may reduce mitochondrial 
dysfunction. Beyond its direct biological effects, optimization of weight may lead to improvements 
in MS-related symptoms such as fatigue as well as in health-related quality of life, as overweight 
MS patients have been shown to have lower self-rated measures of well-being than controls.18,19 As 
such, there is a strong rationale for evaluating the benefits of calorie restriction in MS. The 
timing of calorie intake may also be critical, suggesting a possible rationale for consolidating the 
time period in which typical calories are consumed. 
 
 
2. 
Study Procedures 
a. Study design, including the sequence and timing of study procedures   
 
Calorie restriction study: 
 
Overview: We will conduct a pragmatic pilot study in which 80 patients with MS who are 
undergoing monthly infusions with natalizumab and who are overweight or obese are offered 
enrollment in this trial. Participants who consent will undergo a basic evaluation of total energy 
expenditure. At baseline, participants will participate in a short training about intermittent versus 
continuous calorie restriction and will choose the dietary intervention they’d prefer to use. The 
LoseIt! Application will be installed on the participants’ smartphones, and they will receive 
training in utilizing the application. Baseline assessments of health-related quality of life 
(HRQoL), fatigue, self-esteem and physical activity will be conducted. Serum and plasma will be 
collected for future studies. 
 
Participants will then be randomized to one of two groups: 1) to receiving weekly educational text 
or email messages about the positive health effects of maintaining a normal body mass index, 
particularly as it relates to MS, or 2) standard of care (no additional contact). At the routinely-
scheduled infusions at months 3 and 6, body mass index, waist circumference, and 
fatigue/HRQoL/self-esteem will be evaluated. Serum and plasma will be collected for future 
studies. 
 
Enrollment and Randomization: In order to maximize enrollment within the period of support, 
people with MS who receive monthly natalizumab infusions and meet other criteria (see #3 
inclusion/exclusion criteria) will be offered participation in the study. Potential participants may 
be notified when receiving their regularly scheduled appointment reminder phone call that a study 
team member may approach them during their upcoming infusion visit about enrollment in the 
study. The Johns Hopkins MS Center infusion center currently provides natalizumab infusions for 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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140 MS patients per month; it is estimated that two-thirds have a body mass index ≥ 25 kg/m2. 
Participants will be randomized by the study statistician 1:1 to the frequent patient activation arm 
or standard of care. 
 
Study Procedures/Schedule of Events: 
 
Patients will be consented one month prior to the baseline visit so they can be given adequate 
notice and can be given a stool sample collection kit to bring it at their next infusion. At the 
consent visit, baseline energy requirement will be determined (see below) and the patient’s waist 
circumference will be measured. Waist circumference will be measured according to NIH 
protocol (patient standing with feet shoulder width apart, arms crossed over chest, and abdominal 
muscles relaxed, with measurement taken at the top of the iliac crest, at the end of normal 
expiration). 
 
At the baseline visit, the following will be done: 
• Vital signs and waist circumference 
i. If waist circumference varies ≥10% from the consent visit, baseline 
energy requirement will be re-calculated 
• Patient-Determined Disease Steps 
• Health-related quality of life, (Functional Assessment in MS [FAMS]), fatigue 
(PROMIS fatigue), Pittsburgh Sleep Quality Index (PSQI), timing of sleep 
(Morningness-Eveningness Questionnaire [MEQ]), self-esteem (Rosenberg Self-Esteem 
Scale) and physical activity (International Physical Activity Questionnaire) assessments  
• Blood for future research collected (30 ml) 
• Coaching about the two diet options 
• Installation of LoseIt! application on smartphone 
• Determination of baseline energy requirement (see below) 
• Randomization group assigned (participant blinded) 
• Stool sample kit collection 
 
At follow-up visits (months 3 and 6), the following will be done: 
• Vital signs and waist circumference 
• Patient-Determined Disease Steps (month 6 only) 
• Health-related quality of life (Functional Assessment in MS [FAMS]), fatigue 
(PROMIS fatigue), Pittsburgh Sleep Quality Index (PSQI), timing of sleep 
(Morningness-Eveningness Questionnaire [MEQ]), self-esteem (Rosenberg Self-Esteem 
Scale) and physical activity (International Physical Activity Questionnaire) assessments 
• Blood for future research (30 ml/visit) 
• Stool sample kit distribution (at month 3) and collection (at month 6) 
• Collection of LoseIt! application data (calorie counts) since prior visit 
 
Determination of Baseline Energy Requirement and Diet Details: The baseline energy 
requirement (total energy expenditure) of each participant will be determined prior to 
randomization. This measurement is defined as the number of calories needed to maintain the 
current body weight. Total energy expenditure will be assessed using validated equations from 
University of Arizona Calorie Need Estimates, which include an individual’s estimated resting 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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Version 3 Dated:   06/2007 
 
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energy expenditure (based on current weight, height and age) and physical activity (based on the 
International Physical Activity Questionnaire short form).  
 
Participants will receive education about two diet approaches: intermittent calorie restriction and 
continuous calorie restriction. For the intermittent calorie restriction group, a standardized 
percentage reduction to 25% of the baseline energy requirement will be used two days a week. 
For the continuous calorie restriction group, the same percentage calorie reduction will be 
provided, but the restriction will take place over an entire seven-day period (i.e. the group will be 
provided with food containing 78.6% of their baseline energy requirement (calories) each day. All 
participants will be encouraged to drink water liberally to stave off hunger. If a participant in one 
group is unable to follow their chosen diet, rather than losing the subject as a drop-out, the subject 
will switch to other dietary approach.  
 
Adherence Intervention: All subjects will be asked to document adherence using the LoseIt! 
application, which tracks calorie intake based on food items and quantity consumed. The 
application will be installed on the subjects’ smartphones at the baseline visit, and they will be 
instructed how to use it.  
 
Subjects will be randomized 1:1, stratified by week of enrollment, to receive electronic adherence 
support or to the standard of care (no additional contact). The stratified randomization was chosen 
because participants often receive their infusions at the same time due to the 28-day dosing 
schedule, and thus may otherwise discuss their impressions of the study with other participants 
who happen to be infused at the same time. Those who are in the intervention arm will be sent a 
text message once a week providing encouraging information about the health benefits of weight 
loss and, where possible, specifically focusing on how it may benefit their MS. They will be asked 
to send the previous week’s log of calories consumed to the research group (this information is 
readily available using the LoseIt! application).  
 
Calorie Timing Study 
 
Overview: We will conduct a pragmatic pilot study in which 40 patients with MS who are 
undergoing monthly infusions with natalizumab and who are either not overweight or obese, or 
who do meet criteria for the calorie restriction study but refuse to participate, are offered 
enrollment in this trial. At baseline, participants will be assessed to ensure they know how to take 
pictures with and save them on their smartphones. Baseline assessments of health-related quality 
of life (HRQoL), fatigue, self-esteem and physical activity will be conducted.  
 
Participants will then be randomized to one of two groups: 1) to not changing their current dietary 
patterns at all, or 2) to consuming their total daily calories within a period of 12:00 PM and 8:00 
PM. Serum and plasma will be collected for future studies. 
 
Enrollment and Randomization: In order to maximize enrollment within the period of support, 
people with MS who receive monthly natalizumab infusions and meet other criteria (see #3 
inclusion/exclusion criteria) will be offered participation in the study. The Johns Hopkins MS 
Center infusion center currently provides natalizumab infusions for 140 MS patients per month; it 
is estimated that one-third have a body mass index < 25 kg/m2. Participants will be randomized by 
the study statistician 1:1 to the frequent patient activation arm or standard of care. 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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Study Procedures/Schedule of Events: 
 
Patients will be consented one month prior to the baseline visit so they can be given adequate 
notice and can be given a stool sample collection kit to bring it at their next infusion.  
 
At the baseline visit, the following will be done: 
• Vital signs and waist circumference 
• Patient-Determined Disease Steps 
• Health-related quality of life, (Functional Assessment in MS [FAMS]), fatigue 
(PROMIS fatigue), Pittsburgh Sleep Quality Index (PSQI), self-esteem (Rosenberg 
Self-Esteem Scale), and physical activity (International Physical Activity 
Questionnaire) assessments  
• Blood for future research collected 
• Evaluation of capacity to take and store photos on phone 
• Randomization group assigned (participant blinded) 
• Stool sample kit collection 
 
At follow-up visits (months 3 and 6), the following will be done: 
• Vital signs and waist circumference 
• Patient-Determined Disease Steps (month 6 only) 
• Health-related quality of life (Functional Assessment in MS [FAMS]), fatigue 
(PROMIS fatigue), Pittsburgh Sleep Quality Index (PSQI), and physical activity 
(International Physical Activity Questionnaire) assessments 
• Blood for future research 
• Stool sample kit distribution (at month 3) and collection (at month 6) 
• Collection of photographic data since prior visit 
 
 
b. Study duration and number of study visits required of research participants. 
The study duration is 6 months from the baseline visit. Follow-up visits will be done at the 
patients’ scheduled infusion appointments at months 3 and 6.  
 
c. Blinding, including justification for blinding or not blinding the trial, if applicable. 
Subjects will be blinded to the study hypothesis that additional electronic support will help 
improve dietary adherence, which could influence and confound the results. Subjects will be 
told that the study is evaluating how easily changing calorie amounts or timing can be done in 
the real world and that, in addition to the baseline education, they may receive periodic contact 
from the study team via text message. For the calorie restriction study, both groups will receive 
reminder text messages about the month 3 and 6 study visits, which will help prevent 
unblinding. Further, the randomization strategy employed (clustered by week of baseline visit) 
will prevent contamination of patients who may discuss the study while getting infused, since 
the infusions are scheduled on an every 28-day basis and thus participants would co-mingle in 
the infusion center and may discuss their experience of the study. For the calorie timing study, 
participants will be sent text messages in the morning twice a week instructing them to capture 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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all foods and beverages they consume in the next 24 hours on their smartphone and to save 
those photos. 
 
d. Justification of why participants will not receive routine care or will have current therapy 
stopped.  
This study does not require any changes to the participants’ medical therapies, and they will 
continue to receive routine care. 
 
e. Justification for inclusion of a placebo or non-treatment group. 
The non-treatment group in the calorie restriction study is necessary in order to compare diet 
adherence with the intervention group. This will help us determine whether additional support 
without too much additional human effort actually helps overweight and obese people with MS 
adhere to a dietary intervention. The non-treatment group will still be receiving standard of care. 
The non-treatment group in the calorie timing study will otherwise receive standard of care 
therapy, and no know risks are associated with continuing food intake as is currently done. 
 
f. Definition of treatment failure or participant removal criteria. 
Patient may be removed from this trial if they become pregnant or develop another condition 
that the investigator believes may put them at risk from ongoing participation. 
 
g. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely. 
When the study ends, or if a participant’s participation in the study ends prematurely, they will 
no longer receive electronic communication from the research team, but will be able to continue 
using the LoseIt! application on their smartphone.  
 
3. 
Inclusion/Exclusion Criteria 
 
Calorie Restriction Study: 
 
Criterion 
Rationale 
Age 18-75 years; meets 2010 criteria for 
MS 
To ensure broadly generalizable to the MS 
patient population  
Body mass index (BMI)≥ 25 kg/m2 
To ensure that diet does not lead to too low a 
BMI;13 restricting BMI to exclusively obese 
patients (>30 kg/m2) reduces ability to 
measure safety in non-obese and 
generalizability; limiting to only overweight 
patients (e.g. 25 - 30 kg/m2) reduces 
generalizability.  
No history of diabetes requiring 
medication 
To avoid unpredictable hypoglycemia 
Not pregnant, willing to avoid becoming 
pregnant during the study, and not 
breastfeeding 
To avoid danger to fetus or threats to milk 
supply or health 
No history of an eating disorder 
To prevent relapse of eating disorder 
No current use of warfarin 
To avoid INR fluctuations 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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No history of major surgery within past 
3 months 
To prevent improper wound healing 
Have a smart phone with the capability 
to download and utilize the LoseIt! 
application 
To log food intake throughout the study 
duration, so adherence to diet modification 
may be assessed. 
 
 
 
Calorie Timing Study: 
 
Criterion 
Rationale 
Age 18-75 years; meets 2010 criteria for 
MS 
To ensure broadly generalizable to the MS 
patient population  
Body mass index (BMI)< 25 kg/m2, or if 
higher, participant was unwilling to 
enroll in calorie restriction study 
Only want to enroll overweight or obese 
individuals if they are unwilling to restrict 
calories, as calorie timing study unlikely to 
lead to weight loss 
No history of diabetes requiring 
medication 
To avoid unpredictable hypoglycemia 
Not pregnant, willing to avoid becoming 
pregnant during the study, and not 
breastfeeding 
To avoid danger to fetus or threats to milk 
supply or health 
No history of an eating disorder 
To prevent relapse of eating disorder 
No current use of warfarin 
To avoid INR fluctuations 
No history of major surgery within past 
3 months 
To prevent improper wound healing 
Have a smart phone with the capability 
of taking and storing photographs 
To provides study team with time stamps 
indicating timing of oral intake. 
 
4. 
Drugs/ Substances/ Devices 
a. The rationale for choosing the drug and dose or for choosing the device to be used. N/A 
b. Justification and safety information if FDA approved drugs will be administered for non-FDA 
approved indications or if doses or routes of administration or participant populations are 
changed. N/A 
c. Justification and safety information if non-FDA approved drugs without an IND will be 
administered. N/A 
 
5. 
Study Statistics 
a. Primary outcome variable.  
Calorie restriction study: Change in waist circumference 
Calorie timing study: Change in metabolism biomarkers 
 
b. Secondary outcome variables. 
Calorie restriction study: Change in body mass index, number of pounds lost, percentage 
adherence to recommended calorie intake, changes in health-related quality of life, changes in 
fatigue and sleep 
Calorie timing study: Adherence to photographing foods, changes in health-related quality of 
life, fatigue, and sleep 

 
Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
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c. Statistical plan including sample size justification and interim data analysis. 
 
Summary statistics (mean ± standard deviation, median and interquartile range, or number and 
percentages) will be used to describe the outcomes.  
 
Calorie Restriction: 
 
For the primary objective, the impact of increased patient engagement via the smartphone on 
weight loss (pounds lost, change in body mass index, and change in waist circumference) as 
well as on the percentage adherence to the recommended calorie intake (as assessed by LoseIt! 
logs) will be evaluated in t-tests. If there are baseline imbalances in potentially meaningful 
covariates despite randomization, multivariate approaches accounting for imbalanced covariates 
will be employed.  
 
For the secondary objective, the primary analysis will evaluate the association of weight loss 
(change in body mass index as well as change in waist circumference) with changes in health-
related quality of life, sleep and fatigue using multivariate linear regression adjusted for age, 
sex, race, change in physical activity and baseline disability. Whether group assignment (extra 
smartphone engagement or standard of care) influences this relationship will also be evaluated. 
 
The rationale for measuring change in waist circumference as the primary outcome is that waist 
circumference, rather than body mass index, is considered a better measure of the risk of 
metabolic syndrome.20 However, for comparability with previously-published studies and in 
order to further evaluate the relationship between waist circumference with body mass index, 
both measures will be obtained. 
 
Calorie Timing: 
 
Metabolomics will be conducted on samples from the participants to evaluate the impact of 
restricting the hours in which foods are consumed. Primary analyses will be intent-to treat; 
secondary analyses will investigate with the actual time of day metrics, as assessed by time 
stamps of smartphone photos, are predictive of changes in metabolism. Secondary outcomes 
will be assessed as above. 
 
d. Early stopping rules. 
Participants who become pregnant, experience weight loss with BMI<20 kg/m2, or who develop 
another issue that, in the estimation of the investigator, puts them at risk of ongoing 
participation, the participant will be asked to cease following the diet but will be followed to the 
completion of the study. 
 
6. 
Risks 
a. Medical risks, listing all procedures, their major and minor risks and expected frequency. 
• Calorie-restriction diet  
o The risks associated with the diets are not known 
o Previous studies of similar diets in humans have not shown any serious risks.  
o  

 
Date:  7/20/16    
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•  
• Calorie timing diet 
o Participants may be hungrier in the time in which foods are not being consumed 
 
• Venous blood collection 
o Minimal risk of discomfort, bleeding, bruising or infection at needle entry site 
o Rare risk of vasovagal symptoms or syncope  
o Patients are already getting IV placed for their standard of care treatment, from 
which blood can be drawn to minimize need for additional venipuncture. 
 
b. Steps taken to minimize the risks. To avoid risks associated with phlebotomy, proper safety 
precautions and standard techniques will be followed.  
 
c.   Plan for reporting unanticipated problems or study deviations. This is a low-risk study, and  
no major problems are anticipated. We will use the National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.0 to report and grade all adverse 
events, whether or not they are related to disease progression or treatment. The relationship 
between an adverse event and the dietary intervention will be determined by the PI. We will 
appoint a medical monitor and will report diet-related, unexpected serious adverse events to that 
person and to the IRB within 2 business days. We will provide the medical monitor a log of 
adverse events at the time of continuing review submission to the IRB annually. Minor study 
deviations will also be reported to the monitor and to the IRB annually. 
 
d. Legal risks such as the risks that would be associated with breach of confidentiality. 
Standard procedures will be used to protect patient privacy. Only authorized members of the 
study team will work on the study. Study files and documents will be kept in password-
protected, encrypted computers or in locked offices. There are no known legal ramifications 
associated with breach of confidentiality, however, given current legislation preventing 
discrimination related to a health care condition. 
 
e. Financial risks to the participants. 
There are no known financial risks to participants.  
 
7. 
Benefits 
a. Description of the probable benefits for the participant and for society. 
For the calorie restriction study, the participants may benefit from the study by losing weight, 
which could potentially improve levels of fatigue and health-related quality of life. Potential 
benefits to society include more knowledge about methods to improve adherence to calorie 
restriction diets. This could benefit both patients with MS as well as society in general. There 
are no known benefits for the calorie timing participants. 
 
8. 
Payment and Remuneration 
a. Detail compensation for participants including possible total compensation, proposed 
bonus, and any proposed reductions or penalties for not completing the protocol. 
No payment is available.  
 
9. 
Costs 

 
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a. Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify 
who will pay for them. 
 
The study procedures will be paid for by the investigators. The LoseIt! application is free. Thus, 
there are no costs for participants.  
 
 
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9. Marrie RA, Elliott L, Marriott J, Cossoy M, Tennakoon A, Yu N. Comorbidity increases the risk of 
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Date:  7/20/16    
Principal Investigator: Ellen Mowry, MD, MCR 
Application Number: IRB00095554 
 
 
 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
Page 13 of 13 
 
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AE, Haughey NJ, Lublin FD, Casaccia P. Cerebrospinal fluid ceramides from patients with multiple 
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