Clinical Evaluation of an External Neuromodulation Device (VibraCool) to Reduce Pain and Opioid Use After Anterior Cruciate Ligament Reconstruction (ACLR)
Phase: NA
Conditions: ACL, Opioid Use, Cryotherapy Effect, Vibration; Exposure, Pain, Postoperative
Sponsor: Columbia University

Clinical Evaluation of an External Neuromodulation Device (VibraCool) to Reduce Pain 
and Opioid Use After Anterior Cruciate Ligament Reconstruction
ClinicalTrials.gov ID: NCT06456268    
   
Protocol Date: June 14, 2024
Neuromodulation to Reduce Pain After ACLR
Michael A. Mastroianni, MD (Medical Doctorate)a  
Beth Ashinsky, MD, PhD (Medical Doctorate, Doctor of Philosophy)a 
Michaela O’Connor, MD (Medical Doctorate)a 
Kyle Obana, MD (Medical Doctorate)a 
Christian Law, BS (Bachelors of Science)a 
Robert A. Christian, MD (Medical Doctorate)a 
David P. Trofa, MD (Medical Doctorate)a 
Hasani Swindell, MD (Medical Doctorate)a  
William N. Levine, MD (Medical Doctorate)a 
Lauren H. Redler, MD (Medical Doctorate)a  
aColumbia University Irving Medical Center/NewYork Presbyterian Hospital 630 West 168th 
Street, New York, NY 10032, USA
Keywords: ACL reconstruction, ACL injury, opioids, neuromodulation, post-operative pain
No acknowledgements. 
Correspondence: 
Lauren H. Redler, MD
622 W 168th St, PH-11
Room xxx
New York, NY 10032
lr2505@cumc.columbia.edu

Introduction:
Opioid use after surgery has been identified as a primary contributor to addiction, both 
directly and through increased opioids in circulation [1]. The incidence of opioid addiction 
increases three days after outpatient use [2, 3], and the average duration of opioid use for many 
surgical patients exceeds this duration [4]. As such, opioid-sparing pain relief options are needed 
to address this issue and reduce the potential for dependence and global misuse.
While opioid-reducing consensus statements exist for hip and knee arthroplasty [12], no 
similar guideline exists for ACL reconstruction (ACLR) [13]. Current methods to decrease 
ACLR pain include surgical techniques and post-operative medications including non-steroidal 
anti-inflammatory medications and opioids [14]. Prescription amounts varied widely by 
geographic region, with an average of 87% of patients filling an opioid prescription within 30 
days of surgery in 2017 [14]. 
Cryotherapy has also been used as an adjunctive post-operative therapy to reduce pain 
and inflammation following UCLR. It has been shown to decrease local metabolism, resulting in 
reduced pain and inflammation [cite Crystal et al]. Multiple studies have shown the benefits of 
using cryotherapy after ACLR [cite Raynor et al, Blakeley et al], and more recently dynamic 
intermittent compression has been shown to improve circulation while reducing the risk of skin 
necrosis associated with static permanent compression [cite Khanna et al, McGuire et al]. A 
recent meta-analysis including ten RCTs found significant reductions in post-operative VAS pain 
scores and breakthrough opioid consumption when using cryotherapy, such as Game Ready ice 
therapy, following ACLR [cite Davey et al].

Multiple studies have shown that vibration sources applied to muscles prior to exercise 
reduced soreness and lactate dehydrogenase production, and increased range of motion at 48 and 
72 hours [5-11]. Acute pain results from fast A nerves transmitting nociceptive information to the 
dorsal column, where the substantia gelatinosa’s interneurons prioritize competing A 
mechanoreceptor and C-fibers to slow pain transmission. Melzack and Wall observed that 
stimulation of A mechanoreceptors “shut the gate” on pain transmission, an inhibitory 
mechanism known as “gate control” [5]. Multiple physical methodologies leverage gate control 
physiology for pain relief, such as vibratory massage therapy and electrical stimulation to 
varying degrees [7]. However, the use of vibratory massage to improve pain control and reduce 
opioid use following ACLR has not been well studied, and to our knowledge there are no RCTs 
evaluating the use of this modality compared to standard ice or cryocompression.
Therefore, the primary objective of this study is to test the effects of the FDA-approved 
VibraCool mechanical stimulation and neuromodulatory therapeutic device on post-operative 
pain and opioid use following ACLR, compared to standard ice therapy and cryotherapy. Our 
secondary objective was to determine the degree these treatment modalities reduced the amount 
of residual opioids in circulation. 
Methods:
Study Design:
Surgeons participating in the study will agree to a standard prescription amount of 
opioids (the standard of care, 15 tablets post-operatively with instructions for every 6 hours as 
needed) and a standardization of postoperative ice therapy (i.e., ice pack application usage to 20 
minutes 3 times per day). The standard ice packs control group will apply the ice pack as usual, 

while the remaining treatment arms will place the ice pack in the VibraCool or Game Ready 
machines and place it on their leg for 20 minutes 3 times per day. Pediatric and adult subjects 
with surgical plans to undergo ACL reconstruction will be identified and approached. 
Subjects were randomized to one of the three treatment arms. Subjects randomized to the 
intervention VibraCool group will still receive the standard of care in addition to the intervention. 
Subjects randomized to the intervention groups will be given a one-sheet instruction for use of a 
VibraCool Pro at their pre-operation visit and a link to a video explaining its use. The same will 
be done for the Game Ready treatment arm. Questions about use will be answered by a study 
coordinator, video instruction, or a provider. Study personnel will instruct patients in both groups 
on a 10 cm visual analog (VAS) pain scale using a script, and on a daily analgesic diary. Both 
groups will then record daily logs of pain and opioid use for 7 days. The home pain diary will 
include a Numeric Rating Scale of 0-10 which will be explained prior to discharge, as well as 
daily ratings of pain prior to any pain relief interventions, additional medications and dosages, 
and any comments detailing pain related activities. Qualitative assessment of pain will also be 
completed. On day seven, subjects will complete the patient-reported outcomes measurement 
information system (PROMIS) instrument 8a (adult form for ages 18+ or the pediatric form) for 
pain interference will be completed. The study will be complete at 7 days. 
REDCap was used to record patient responses on a daily basis, with daily patient portal 
or phone call reminders. The daily survey also contained a video on how to use the device so 
patients have easy access to detailed information on how to use the device, in addition to our 
team being available to address any issue. Multiple factors have been shown to influence pain, 
including anxiety and/or depression, age, severity of preoperative pain, smoking, alcohol use, 
and socioeconomic status [16-20]. These characteristics were collected for each patient in our 

study to account for potential confounders. Classically, pain has been rated on a numerical scale, 
which gives little perspective into the degree of impact on an individual's function and quality of 
life. A more insightful measure may be Pain Interference (PI), known as “pain impact,” which 
has been shown to be a more insightful measure into how pain interferes with an individual's 
physical, mental, and social quality of life and has been deemed a key outcome in pain clinical 
trials, especially in orthopedics [21-23].
Potential subjects are identified as those pediatric and adult patients who are indicated for 
ACL reconstruction surgery. Pediatric iliotibial band (ITB) ACLR and non-English speakers 
were excluded secondary to xxx and limitations of our study group. Patients (and in appropriate 
cases, their parents or guardians) will be notified of the study and its procedures by the treating 
orthopedic surgeon or other study member listed on this IRB. Consent will be obtained either in 
the office or via phone a telehealth visit, the study will be explained in full during visit, then re-
explained with consent to be signed in the pre-operative area, at which time the patient will be 
randomized as described above. The informed consent process as a whole presents information 
in sufficient detail relating to the research study, and informed assent was also obtained for every 
subject below the age of 18. 
Statistical Analysis:
The primary outcome will be daily mean VAS pain scores over the first seven post-
operative days and percent of patients discontinuing opioid use by or on post-operative day three, 
compared to those who continue after day three. Secondary outcomes include mean reduction in 
opioid use in milligrams of morphine equivalents per day (MMOD) of 30% from patients not 
using the device over the 7-day period and pain interference scores. A descriptive analysis of the 
demographic and physiological data will be performed using proportions, frequency 

distributions, medians, and confidence intervals. Statistical testing will include ANOVA analysis 
and unpaired t-tests for continuous variables between the treatment arms, while chi squared 
analysis will be used for categorical variables. Subgroup analysis by graft type was conducted 
similarly. 
Based on a previous ACL pilot study using a single vibration unit, 71% discontinued 
opioids by day 3, compared to only 40% in a published cohort. Therefore, 38 patients will be 
needed in each group. Assuming a 15% drop-off, 44 patients will need to be recruited for the 
device versus nothing group to give 80% power, or 88 subjects total. Previous studies comparing 
two modalities suggest a standard deviation of 1.8. 20 patients in each group will have power of 
0.87 to detect a difference in the means of 1.8 cm mean VAS pain score reduction between 
nothing and study device with the same alpha criterion. The study will be underpowered to detect 
an overall difference in opioid use based on the assumed effect size of .58 (Cohen’s D) – 0.62 
(Hedges’ g) for the primary outcome variable (opioid use) based on 10.1+/- 10.3 (n=14) 
compared to 15.6+/-8.5 (n=77). The criterion for significance (alpha) is 0.05
Results:
Discussion:
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