A Randomized Prospective Study on the Efficacy of the MMF07 Foot Massager and Heat Therapy Treatments for Restless Leg Syndrome
Phase: NA
Conditions: Restless Legs Syndrome
Sponsor: Ariane Park

Research Protocol 
 
 
 
A randomized prospective study on the efficacy of the MMF07 Foot 
Massager and heat therapy treatments for Restless Legs Syndrome 
 
NCT02526277 
 
Version 10-16-2015 
 
 
Principal Investigator: 
Ariane Park, MD, MPH 
Assistant Professor 
Department of Neurology 
395 W. 12th Ave., 6th Floor 
Columbus, OH 43210 
Email: Ariane.Park@osumc.edu 
Phone: 614-293-4969 
Fax: 614-293-6111 
 
Co-Investigators: 
Kathleen Moore CNP 
Nurse Practitioner 
Department of Neurology 
395 W. 12th Ave., 7th Floor 
Columbus, OH 43210 
Email: kathleen.moore@osumc.edu 
Phone: 614-293-4969 
Fax: 614-293-6111 
 
Key Personnel: 
Katherine Ambrogi RN 
Clinical Research Coordinator 
Neurology 
2006 Kenny Road 
Columbus, OH 43210 
Email: katherine.ambrogi@osumc.edu 
Phone: 614-688-6685 
 
Statistician: 
Allison M. Wehr, MS 
Biostatistician 
Center for Biostatistics 
2012 Kenny Road 
Columbus, OH 43221 
Email: allison.wehr@osumc.edu 
Phone: 614-293-2999 
 
 
 

 
 
A randomized prospective study on the efficacy of the MMF07 Foot Massager and 
heat therapy treatments for Restless Legs Syndrome 
 
 
 
 
 
I. Study Objectives 
 
We propose to conduct a prospective clinical trial using a 2 x 2 factorial design;  
patients with restless legs syndrome (RLS) will be randomized to one of four treatment 
arms:  no intervention, MMF07 Foot Massager device alone, heating therapy alone, and 
MMF07 Foot Massager device plus heating therapy.  
 
Few clinical trials have looked into non-pharmacologic, non-invasive treatments for 
restless legs syndrome, despite reports that massage, baths and vibration can alleviate 
RLS symptoms.  We would like to assess whether the MMF07 Foot Massager device 
and/or heating therapy is associated with improved severity of restless legs symptoms as 
measured by the International Restless Legs Severity Scale.  Secondary outcomes 
include evaluating potential changes in both quality of life and sleep as measured by the 
Restless Legs Quality of Life Questionnaire and Medical Outcomes Sleep Study scale, 
respectively.  Current therapies for RLS are limited, therefore investigating effective 
non-invasive treatments that attenuate symptoms would be an important advancement in 
the treatment of this aggravating disease. 
 
II. Background and Rationale 
 
Restless legs syndrome (RLS) is characterized by abnormal, uncomfortable sensations, 
typically present in the legs, which are temporarily relieved by movement. The 
pathophysiology of RLS is unknown.  Several theories exist, including microvascular 
abnormalities (1), peripheral hypoxia (2) and changes in dopaminergic pathways which 
may lead to lower iron levels in the brain (3). 
 
Pharmacologic treatments for RLS include dopamine agonists, anti-epileptics, 
benzodiazepines and opiates.   There is limited data supporting the use of clonidine, 
baclofen, tramadol and magnesium as first- or second-line therapy.  Iron 
supplementation, orally or intravenously, is recommended for patients with low serum 
ferritin levels. The only randomized, double-blind, placebo-controlled study that 
evaluated oral iron therapy for RLS did not provide sufficient evidence to show that iron 
sulfate was a good empiric treatment for RLS (4).   
 
There are limitations to pharmacologic therapies.  For example, dopaminergic 
medications, considered the gold standard treatment for RLS, are associated with 
“augmentation,” a phenomenon characterized by RLS symptoms that start earlier in the 

daytime, and ascend up the body, sometimes involving the arms and trunk.  Also, 
dopaminergic therapies are associated with impulse control disorders, such as punding, 
pathologic gambling, binge eating and hypersexuality.  Anti-epileptics, benzodiazepines 
and opiates can cause sedation, dizziness and mood changes. 
 
Non-pharmacologic therapies that have been evaluated for the treatment of RLS include 
enhanced external counterpulsation (EECP) (5), sclerotherapy (6), deep brain stimulation 
therapy (7), and acupuncture (8).  Non-invasive treatments that are recommended for 
RLS patients include warm or cool baths, massage, exercise, and staying mentally active 
as symptoms can be triggered when patients are bored.  To our knowledge, there have 
been no clinical trials evaluating the efficacy of heating therapy in treating RLS 
symptoms.  A recent study showed that external sensory input may lead to less leg 
discomfort in RLS (9).  In May 2014, the Food and Drug Administration (FDA) granted 
commercial clearance for the Relaxis Pad to be marketed for improvement in the quality 
of sleep for patients with primary RLS.  This device, developed by Sensory Medical, is a 
vibrating pad that patients can place at their site of discomfort while remaining in bed.  A 
four week study published in a non-MEDLINE-indexed journal found that treatment with 
such vibrating pads safely improved sleep in patients with RLS (10). 
 
Given this knowledge gap in the realm of non-pharmacologic, non-invasive treatments 
for RLS, our study aims to explore whether the MMF07 Foot Massager and/or heating 
therapy may alleviate the symptoms of RLS. 
 
III. Procedures 
 
 
A. Research and Design 
 
Subject Selection/Sample 
 Inclusion criteria: 
1) Patients between 18-75 years old diagnosed with RLS according to the 
diagnostic criteria of the International Restless Legs Syndrome Study Group 
(11). 
2) Subjects should have bothersome RLS symptoms, despite best medical 
therapy 
3) Subjects should be stable on all RLS medication for at least 4 weeks prior to 
enrollment  
4) All subjects must be able to read and write in English in order to be able to 
complete home diary cards and questionnaires.   
5) All women of childbearing age must be using an acceptable form of birth 
control, including abstinence, IUD or intrauterine system in place for at least 
3 months prior to screening, subject or partner using barrier method (e.g., 
condom, diaphragm, or cervical cap) with spermicide from screening 
through study completion; partner has a documented vasectomy > 6 months 
prior to Baseline, Stable hormonal contraception (with approved oral, 
transdermal, or depot regimen) for at least 3 months prior to screening. 
 

 Exclusion criteria: 
1) RLS secondary associated with end stage renal disease, iron deficiency or 
pregnancy 
2) Concomittant sleep disorders 
3) Does not have sufficient vision to be compliant with study procedures.  
4) Any other condition (other than the primary indications), which in the 
opinion of the investigators might contribute to difficulty complying with the 
protocol 
 
 
 
 
 
No Intervention 
 
Patients receiving no intervention will be asked to not alter their nighttime 
 
routine.   
 
MMF07 Foot Massager 
 
The MMF07 Foot Massager is manufactured by Medmassager, a company 
located in Arden, NC.  The MedMassager brand has been on the market for five 
years, but versions of this type of massager have been sold in the United States 
for almost 30 years.  The MMF07 is engineered in an International Organization 
for Standardization (ISO) 9001-2008 manufacturing facility and is Canadian 
Standards Association (CSA) certified for safety and reliability.  The massager 
is FDA certified for therapeutic use under regulation number: 890.5660. 
 
 
The MedMassager MMF07 utilizes a circular motion footplate to stimulate 
circulation in the lower extremities.  Rather than an up and down, vibrating 
motion which could cause too much stress, the MMF07 moves the feet and legs in 
a circle 20 microns in diameter. The unit has a variable controller that can be 
manually adjusted, allowing for more or less stimulation. 
  
The unit is constructed of an ABS plastic shell and footplate frame and a 
hypoallergenic footpad surface. The motor is mounted to a metal sub frame and 
attached to the footplate frame with a 20 micron bearing and insulation cap.  The 
unit has a 10 foot power cord allowing easy access to receptacles without the need 
for an extension cord. 
 
To operate this device, the power supply cord needs to be inserted into an 
electrical outlet when the speed switch is in the OFF position.  The unit should 
be turned to the desired speed.  When finished, the switch should be turned back 
to the OFF position, and unit should be unplugged. 
 

The unit has never been tested clinically before. The only adverse effect that has 
been reported by users to the manufacturer is an itchy sensation in the feet 
and/or legs during use.   
 
Patients randomized to either the MedMassager MMF07 only or MedMassager 
MMF07 and heating therapy cohort will be instructed to set this device at setting 
3, then increase or decrease the setting to their desired level of comfort.  They 
will be instructed to use this device for thirty minutes at bedtime.  Patients will 
be provided with a home diary to record duration and device setting on a nightly 
basis. They will be asked to otherwise not alter their nighttime routine.   
 
 
 
Heating Therapy 
 
 
Patients randomized to either the heating therapy only or MedMassager MMF07 
and heating therapy cohort will be given an electric heating pad, and they will be 
instructed to use this pad at the medium setting for thirty minutes at bedtime.  
They can adjust the setting to their level of comfort if needed. They will be 
provided with a home diary to record duration and pad setting on a nightly basis. 
Patients will be asked to otherwise not alter their nighttime routine.   
 
 
B. Measurement/Instrumentation 
 
1) International Restless Legs Severity Scale (12): a 40 point scale measuring 
severity of restless leg symptoms.  Patients are asked to answer a series of 10 
questions each of which have values ranging from 0 to 4 and the points are then 
added.  Higher values are associated with more severe symptoms.   
2) Restless Legs Quality of Life Questionnaire (13): a series of 18 questions that 
are scored such that lower scores indicate worse quality of life. 
3) Medical Outcomes Sleep Study scale (14): a series of 12 questions assessing 
quality of sleep, with values ranging from 1 to 6 
4) Home diary (see attached) 
 
Visits will be at baseline and at week 4.  Outcome measures will be self-administered at 
each visit.  Medical history including demographic information and information about 
alcohol, drug and tobacco use will be collected at the baseline visit. Medications and 
vital signs will be recorded at each visit.  Urine pregnancy tests will be performed on all 
females of child bearing potential at baseline prior to randomization and again at week 
4. Adverse events will be recorded at week 4 or as reported by the patients.  Home 
diaries will be collected at the week 4 visit.  
 
Anticipated benefits for the subjects in the treatment arms will be attenuation of RLS 
symptoms and improvement in quality of life and sleep. 
 

 
Statistical Considerations:  
 
A. Sample Size: 
A total of 40 patients will be accrued to the study with roughly equal allocation to each 
treatment arm.  This sample size will achieve over 90% power to detect a 5 point change 
in the International Restless Legs Severity Scale for the main effects of heating therapy 
and MedMassager MMF07 assuming a standard deviation of 4 within each cohort.  
Additionally we will have roughly 80% power to detect a potential interaction effect 
between MedMassager MMF07 and heating therapy.  Every effort will be made to reduce 
attrition; consent documents will emphasize the importance of complete data and 
encourage patients to return for the follow-up visit.   
 
B. Randomization: 
Patients will be randomized to one of the four treatment options with equal allocation.  In 
an attempt to balance severity across treatment cohorts the randomization scheme will be 
stratified by baseline severity of RLS symptoms as measured by the International 
Restless Legs Severity Scale (mild/moderate vs. severe/very severe).  The randomization 
scheme will be generated by the study statistician with varying block sizes and uploaded 
to a web-based randomization program.  After the patients eligibility has been confirmed 
and consent documents signed the research coordinator will randomize the patient to one 
of the four treatment options via the web-based randomization program.  The PI will not 
randomize patients or have access to their treatment assignments.  
 
C. Analysis plan: 
All demographic and baseline characteristics of interest will be summarized both overall 
and by cohort.  Frequencies and percentages will be used to summarize categorical 
variables and means, standard deviations and other appropriate measures of spread for 
continuous variables.  ANOVA models will be used for testing and to estimate the effects 
of MedMassager MMF07 alone, heating therapy alone and the potential interaction 
between MedMassager MMF07 and heating therapy.  Sensitivity analyses may be 
considered to assess the impact of baseline severity and other clinically relevant 
covariates on the outcomes.  We will adjust for multiplicity for all contrasts. Secondary 
outcomes will be analyzed using a similar approach.  Further details will be provided in 
the Statistical Analysis Plan (SAP).     
 
 
For study-related patient data (case report forms) a unique identifier will be used.  
Study-related documents will be kept in a locked cabinet in a locked office.  A separate 
list (paper-only) will be made containing the unique identifier and the name of each 
participant.  This list will be kept separate from the study related documents. Study 
databases will be stored on a password protected computer network in a locked office 
and kept for 5 years. 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IV. Bibliography 
 
References 
 
1. 
Anderson KN, Di Maria C, Allen J. Novel assessment of microvascular changes 
in idiopathic restless legs syndrome (Willis-Ekbom disease). Journal of sleep research. 
2013;22(3):315-21. 
2. 
Salminen AV, Rimpila V, Polo O. Peripheral hypoxia in restless legs syndrome 
(Willis-Ekbom disease). Neurology. 2014;82(21):1856-61. 
3. 
Dauvilliers Y, Winkelmann J. Restless legs syndrome: update on pathogenesis. 
Current opinion in pulmonary medicine. 2013;19(6):594-600. 
4. 
Davis BJ, Rajput A, Rajput ML, Aul EA, Eichhorn GR. A randomized, double-
blind placebo-controlled trial of iron in restless legs syndrome. European neurology. 
2000;43(2):70-5. 
5. 
Rajaram SS, Rudzinskiy P, Walters AS. Enhanced external counter pulsation 
(EECP) for restless legs syndrome (RLS): preliminary negative results in a parallel 
double-blind study. Sleep medicine. 2006;7(4):390-1. 
6. 
Kanter AH. The effect of sclerotherapy on restless legs syndrome. Dermatologic 
surgery : official publication for American Society for Dermatologic Surgery [et al]. 
1995;21(4):328-32. 
7. 
Driver-Dunckley E, Evidente VG, Adler CH, Hillman R, Hernandez J, Fletcher 
G, et al. Restless legs syndrome in Parkinson's disease patients may improve with 
subthalamic stimulation. Movement disorders : official journal of the Movement Disorder 
Society. 2006;21(8):1287-9. 

8. 
Hu J. Acupuncture treatment of restless leg syndrome. Journal of traditional 
Chinese medicine = Chung i tsa chih ying wen pan / sponsored by All-China Association 
of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine. 
2001;21(4):312-6. 
9. 
Rozeman AD, Ottolini T, Grootendorst DC, Vogels OJ, Rijsman RM. Effect of 
sensory stimuli on restless legs syndrome: a randomized crossover study. Journal of 
clinical sleep medicine : JCSM : official publication of the American Academy of Sleep 
Medicine. 2014;10(8):893-6. 
10. 
Burbank F, Buchfuhrer M, Kopjar B. Sleep improvement for restless legs 
syndrome patients.  Part I: pooled analysis of two prospective, double-blind, sham-
controlled, multi-center, randomized clinical studies of the effects of vibrating pads on 
RLS symptoms. Journal of Parkinsonism and Restless Legs Syndrome. 2013:1-10. 
11. 
Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. 
Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A 
report from the restless legs syndrome diagnosis and epidemiology workshop at the 
National Institutes of Health. Sleep medicine. 2003;4(2):101-19. 
12. 
Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, et al. Validation 
of the International Restless Legs Syndrome Study Group rating scale for restless legs 
syndrome. Sleep medicine. 2003;4(2):121-32. 
13. 
Abetz L, Vallow SM, Kirsch J, Allen RP, Washburn T, Earley CJ. Validation of 
the Restless Legs Syndrome Quality of Life questionnaire. Value in health : the journal of 
the International Society for Pharmacoeconomics and Outcomes Research. 
2005;8(2):157-67. 
14. 
Hays RD, Stewart, A.L., editor. Sleep measures. Durham, NC: Duke University 
Press; 1992. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Start Date:  _____________________________ 
 
 
 
 
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