Efficacy of the Quell Wearable Device for Fibromyalgia
Phase: NA
Conditions: Fibromyalgia
Sponsor: Brigham and Women's Hospital

 
Title: Efficacy of the Quell Wearable Device for Fibromyalgia 
 
NCT# 03714425 
 
Date: 09/27/2018 
 
 
RESEARCH DESIGN AND METHODS 
 
We will recruit 100 patients (see the power analysis) with a primary complaint of FM and 
randomize each of the subjects to one of two treatment conditions: 1) the regular Quell device, 
and 2) a Minimal Frequency Quell device (control). All participants will be adults age 21 or older 
and diagnosed with FM. Patients will be invited to participate if they own a smartphone (iPhone 
or Android device) and can download the pain app and the Quell Relief program app onto their 
device. Patients will also be included if they (1) have chronic pain related to FM for > 3 months’ 
duration, (2) average 4 or greater on a pain intensity scale of 0 to 10, and (3) are able to speak 
and understand English. A subject will need to meet the criteria set out by Wolfe et al., for 
fibromyalgia to be considered for inclusion in this trial: (1) wide spread pain, (2) pain for 3 
months or longer, and (3) pain that is not accounted for by any other medical condition (see 
Table 2). We will also require that the participants have a “physician diagnosis” of fibromyalgia, 
meaning that they have been told that they have fibromyalgia and the diagnosis was entered in 
a medical record somewhere. 
 
Patients will be excluded from participation if they meet any of the following criteria: (1) 
diagnosis of cancer or any other malignant disease, (2) acute osteomyelitis or acute bone 
disease, (3) present or past DSM-V diagnosis of schizophrenia, delusional disorder, psychotic 
disorder, or dissociative disorder that would be judged to interfere with study participation, (4) 
pregnancy, (5) any clinically unstable systemic illness judged to interfere with treatment, (6) a 
pain condition requiring urgent surgery, (7) an active substance use disorder, such as cocaine 
or IV heroin use (positive on the Mini International Neuropsychiatric Interview; M.I.N.I. v.5.0),  
that would interfere with study participation, and (8) have an implanted cardiac pacemaker, 
defibrillator, or other implanted device. All subjects will be asked to not change their treatment 
during the study period. 
 
Patients will be equally randomized to one of two experimental groups (High Frequency Quell, 
N=50, and Minimal Frequency Quell, N=50). The Minimal Frequency Quell will look exactly like 
the High Frequency Quell but will be programmed to give 2 minutes of stimulation twice during a 
1-hour therapy session (2 minutes of stimulation at 0 and 30 minutes, etc.). All subjects will 
complete assessment measures and be followed for 3 months. Recruitment will not be restricted 
based on race or ethnicity. Efforts will be made to recruit at least 15% minorities.  Since 
fibromyalgia is identified more often among women than men, we anticipate recruiting 10-15% 
males. All participants will get assistance in downloading the pain app and have access to a 
research assistant (RA) who could answer any questions and help manage any problems that 
the individual may encounter. All participants will also be given a battery of QST testing at 
baseline and again at the end of the study. We will use an enriched design by first having the 
potential subjects try the Quell device. We anticipate that less than 5% will decide not to 
participate in a trial because they dislike the feeling of the Quell. If they find that they would like 
to use this device they will be included in the study. If they dislike using the device on an initial 
trial, their age, gender, ethnicity and pain duration will be noted, and the participants will be 
thanked for their interest in the study and dismissed. 

 
All subjects (High Frequency Quell and Minimal Frequency Quell condition) will be encouraged 
to use their device for at least 2 therapy sessions (2 hours of stimulation) every day, and to wear 
the device as often as possible. Tracking of use of the device will be available electronically 
through the NeuroMetrix Quell app. All demographic and daily pain assessment data will be 
stored on a secure server (Veracode tested) at BWH and messages will be sent via the 2-way 
messaging pain app program to help track use of the device. Patients who wish to discontinue 
the study will be allowed to do so at their request. If the participant is willing, we will meet with 
her or him to understand reasons for discontinuing the study and problem-solve to see if there is 
a way to keep following the individual. All subjects will be asked to complete a packet of mailed 
mid-point assessments approximately 6 weeks after the start of the study and return the 
completed assessments in pre-addressed stamped envelopes. All subjects will also be asked to 
complete post-intervention mailed assessments after 3 months. Each subject will be 
compensated $25 at baseline and $50 at study completion upon receipt of their completed 
questionnaires. All subjects will be allowed to keep their Quell device at the end of the study. 
Those subjects assigned to the Minimal Frequency Quell condition will be offered to switch to a 
High Frequency Quell at the end of the 3-month trial period. It is expected that 15% of the 
subjects will dropout before completing the study and recruitment of 115 subjects will be 
needed. 
 
Quantitative Sensory Testing (QST): Mechanical pain: Responses to punctate mechanical 
stimuli will be measured using a standard set of weighted probes that provide estimates of pain 
threshold and mechanical temporal summation. Series of 10 stimuli (with 1-second inter-
stimulus intervals) will be used to assess the temporal summation of pain that occurs with rapid 
administration of identical stimuli. A Somedic pressure algometer will be utilized to assess 
responses to pressure stimulation at several anatomical sites. Pain pressure thresholds (PPT) 
will be determined twice at each of the following sites on the right and left sides of the body: the 
trapezius, and thumb. Mechanical pressure will be applied using a 0.5-cm2 probe covered with 
1mm polypropylene pressure-transducing material; pressure is increased at a steady rate of 30 
kPA/s until the subject indicates that the pressure has become painful. Finally, we will use cuff 
algometry to assess responses to sustained mechanical pressure. A Hokanson rapid cuff 
inflator will be used to inflate a standard blood pressure cuff around the gastrocnemius muscle 
to a moderately painful level for up to 2 minutes. Participants will indicate when the pressure 
first becomes painful (i.e., pain threshold) and will provide pain ratings every 30 seconds. As 
with each of these psychophysical testing procedures, participants are informed that they may 
terminate the procedure at any time. 
 
Cold Pain Assessment: Responses to noxious cold will be evaluated using a repeated cold 
pressor task (CPT), which involves immersion of the right hand in a circulating water bath 
(Neslab RTE17) maintained at a temperature of 4°C. The CPT is the most commonly-used 
method of pain induction in the laboratory and has demonstrated clinical relevance. Participants 
will undergo a series of several cold pressor tasks, with the first 2 consisting of serial 
immersions of the right hand for 30 sec, with 2 min between immersions. Conditioned Pain 
Modulation (CPM, which refers to the phenomenon of one noxious stimulus inhibiting the pain of 
a second noxious stimulus) is measured during these cold pressor trials by assessing PPTh 
during the immersion. The final CPT involves an immersion of the right hand lasting until a 
participant reaches pain tolerance (or a 3 min maximum). Participants will rate the intensity of 
the cold pain on a 0-100 scale (“no pain” to “most intense pain imaginable”). 
 
Blinding: The Minimal Frequency Quell is identical to the High Frequency Quell in all aspects 
with one exception. While the Quell typically delivers 1 hour of continuous stimulation during a 
therapy session, the Minimal Frequency Quell device will deliver only two 2-minute periods of 
stimulation every sixty minutes within each therapeutic session. This limited stimulation should 

have minimal analgesic effect but should suggest to the subject that they are receiving therapy. 
Neither the principal investigator, the co-investigators, the research assistant (RA, who will 
serve as the study coordinator), nor the subject will know if they are given a Minimal Frequency 
or High Frequency Quell device. The devices will be randomly numbered and provided by 
NeuroMetrix. At the end of the study, subjects will be asked if they thought they had the Minimal 
Frequency or High Frequency Quell device. The principal investigator, co-investigators and the 
RAs will be asked to identify which subjects they thought had High Frequency Quell vs Minimal 
Frequency Quell, prior to analysis of the data. Both the High Frequency and Minimal Frequency 
Quell will communicate via Bluetooth with the same mobile application. This application 
provides the subjects with a dashboard of device information, trending data on device usage, 
and sleep quality. This same information will be synced to a cloud so that investigators involved 
in the study can collect this data remotely, as well as monitor adherence with the device. In a 
past unpublished investigation when this blinding procedure was used among 17 subjects and 
11 physicians, Investigators accurately guessed the device (minimal frequency or high 
frequency) a subject was randomized to in 11 of 17 participants (64.7%).  Eleven of 17 (64.7%) 
study participants accurately guessed the device to which they were randomized. However, 
there was some discordance between the subjects and the investigators as to who had the 
minimal frequency versus high frequency devices.  
 
Patient Measures: We will be tracking the patients using validated measures of pain (The Brief 
Pain Inventory - BPI), fibromyalgia (Revised Fibromyalgia Impact Questionnaire – FIQR), coping 
(Pain Catastrophizing Scale - PCS), level of disability (Pain Disability Index - PDI), mood 
(Hospital Anxiety and Depression Scale - HADS), presence of neuropathy (Pain Detect 
Neuropathic Pain Questionnaire – painDETECT), impression of change (Patients’ Global 
Impression of Change – PGIC), healthcare utilization (monthly clinic and ED visits), and overall 
satisfaction (Satisfaction and qualitative questions developed for this study specifically related to 
use of a pain management device; see Table 1). We will also track daily ratings of pain, sleep, 
activity interference, and mood through the pain app. Objective measures of activity, gait, and 
sleep will be collected by the devices. 
 
Research Objectives: This study is expected to take 18 months to complete and is designed to 
gather information about the use of the Quell for persons with chronic fibromyalgia-related pain. 
We hypothesize that those assigned to using the High Frequency Quell device will report 
reduced pain compared with those in the Minimal Frequency Quell condition; with those using 
the High Frequency device also showing improvement in sleep, mood, and level of activity. We 
hypothesize that frequency of using the Quell (increased tolerability and adherence) will be 
correlated with greater reduction in pain. We hypothesize that the device will be safe to use and 
will demonstrate a reduction in healthcare utilization (reduced clinic and ED visits). We will also 
investigate use of prescription opioids and other nonopioid pain medications among the study 
subjects and determine the effect of daily use of the High Frequency Quell (vs. Minimal 
Frequency Quell) on intake of prescription pain medication. Finally, based on preliminary 
analyses limited by few subject numbers, we will investigate whether certain individuals report 
greater benefit from using the Quell than others and, in particular, we predict that those with 
more sensitivity and longer duration of pain will demonstrate most benefit. We will target the 
PGIC as the primary outcome measure, since it gives a global impression of change in pain, 
activity limitation, emotions, and overall quality of life. We will target the BPI, FIQR, PCS, PDI, 
HADS, healthcare utilization, and satisfaction questions as secondary outcome measures.  
 
Power Analyses: Power calculations, as outlined by Cohen (1988), were performed to 
determine the probability of detecting clinically significant differences between treatment groups 
in the primary area of measurement: Patients’ Global Impression of Change – (PGIC).  These 
calculations assumed a two-tailed test and alpha level of 0.05 confirming the hypotheses that 

the Quell would be associated with general overall improvement (e.g., more pain relief, less 
emotional distress, and less activity interference). In our previous work (Jamison, Wan et al, 
submitted), we had a high rate of consent to participate among recruited patients, without any 
significant attrition. We assessed power using a range of plausible parameter values, based on 
our preliminary data and previously published studies. The power analyses revealed that a 
sample size of 100 subjects (50 per treatment group), even with 10% dropout, gives the study a 
>85% probability of detecting a 10-point group difference on a 0-100 rating scale (assuming a 
standard deviation of 16). Conventional metrics suggest that a 30% change, or difference score, 
is clinically meaningful, and this sample size would provide adequate power to detect a group 
difference of approximately 20%. Most of the analyses in the proposed study will involve delta 
scores reflecting changes within subjects, though the primary analysis of PGIC will compare raw 
scores rather than change scores (as the PGIC variable is a patient-reported rating of change). 
Scores of variables used in the secondary analyses should exhibit lower standard deviations 
than those assumed in the power calculations. We will examine the distribution of the delta 
scores between groups and will ascertain whether that distribution is normal. This information 
will allow us to determine whether parametric or nonparametric analyses should be used. 
Collectively, this sample size (n=100 total), together with our previously-observed very high 
retention rates and the substantial efficacy of the device, will provide more than adequate power 
to detect moderate-size effects.