Clinical trial NCT05046639
Conditions: Pain Amputation
Keywords: Pain Amputation Phantom Pain
Sponsor: Northwestern University
Start date: 2021-09-01; Completion date: 2023-07-26
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Participants with chronic, refractory phantom limb pain (PLP) or residual limb pain (RLP) for more than 6 months will be enrolled in this clinical trial. Aim: Define the attributable pain relief and functional improvement in participants with PLP/RLP after contralateral limb sciatic nerve block. Also, contribute to the basic science understanding of the crossed-withdraw reflex by demonstrating a known animal model phenomenon in human participants. Hypothesis: Contralateral limb sciatic nerve anesthetic block with 2% lidocaine provides immediate clinically meaningful pain reduction, defined as the proportion of patients with at least 50% improvement in numeric rating scale (NRS) pain score in PLP/RLP when compared to sham.

Detailed description:

Arms: arm 1: Image guided sciatic nerve anesthetic block of the contralateral limb with an injection of 10 mL 2% lidocaine.

Crossover: Image guided sciatic nerve anesthetic block of the contralateral limb with 10 mL preservative-free saline.

Crossover treatment will occur 5 days after the first block. arm 2: Image guided sciatic nerve anesthetic block of the contralateral limb with an injection of 10 mL preservative free saline.

Crossover: Image guided sciatic nerve anesthetic block of the contralateral limb with an injection of 10 mL 2% lidocaine.

Crossover treatment will occur 5 days after the first block.
Interventions: intervention 1: 10 mL 2% lidocaine intervention 2: 10 mL preservative free saline
Intervention descriptions: intervention 1: Image guided sciatic nerve anesthetic block of the contralateral limb with an injection of 10 mL 2% lidocaine. Crossover treatment 5 days later using image guided sciatic nerve anesthetic block of the contralateral limb with 10 mL preservative-free saline. intervention 2: Image guided sciatic nerve anesthetic block of the contralateral limb with an injection of 10 mL preservative free saline.

Crossover treatment 5 days later using Image guided sciatic nerve anesthetic block of the contralateral limb with an injection of 10 mL 2% lidocaine.

Protocol documents:
Prot_SAP_000.pdf: 
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PROTOCOL TITLE: Sciatic Block in Contralateral Limb for Treatment of Refractory 
Phantom and Residual Limb Pain; a Triple-Blind Randomized Crossover Controlled Trial 
 
 
PRINCIPAL INVESTIGATOR: 
David Walega, MD, MSCI 
Division of Anesthesiology 
312-695-2500 
d-walega@northwestern.edu 
 
 
VERSION DATE: 
Version 1.0 07/14/2021 
 
  
STUDY SUMMARY: 
 
Investigational Agent(s)  
(Drugs or Devices) 
 
Lidocaine 2% 
 
IND / IDE / HDE #  NA 
Indicate 
Special Population(s) 
NA  
Sample Size 20 
Funding Source Internal 
Indicate the type of consent 
to be obtained 
Written 
Site Single  
Research Related Radiation 
Exposure 
Yes  
DSMB / DMC / IDMC No 
 
OBJECTIVES: 
Participants with chronic, refractory phantom limb pain (PLP) or residual limb pain (RLP) for 
more than 6 months will be enrolled in this clinical trial. 
 
Aim: Define the attributable pain relief and functional improvement in participants with 
PLP/RLP after contralateral limb sciatic nerve block. Also, contribute to the basic science 
understanding of the crossed-withdraw reflex by demonstrating a known animal model 
phenomenon in human participants. 
 
Hypothesis: Contralateral limb sciatic nerve anesthetic block with 2% lidocaine provides 
immediate clinically meaningful pain reduction, defined as the proportion of patients with at 
least 50% improvement in NRS pain score in PLP/RLP when compared to sham. 
 
 


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BACKGROUND: 
RLP and PLP affect most amputees at some point in their life1. The incidence of PLP has been 
estimated to range between 50 – 80% 2-8. The prevalence of RLP has been estimated to be 
approximately 40%9. RLP is more common in the first year after amputation, with PLP 
becoming the predominate amputee pain complaint after one-year post-amputation10.  
 
Both RLP and PLP fall under the umbrella term “post-amputation pain.” While these conditions 
are frequently found in combination, their clinical features are distinct and may share a common 
pathophysiological mechanism with neuroma formation9,11. PLP is a painful sensation in the 
distribution of the missing limb. Following amputation, abnormalities at multiple levels of the 
neural axis have been implicated in the development of PLP; changes include cortical 
reorganization, reduced inhibitory processes at the spinal cord, synaptic response changes and 
hyperexcitability at the dorsal root ganglion, retrograde peripheral nerve shrinkage, and neuroma 
formation12-14. 
 
RLP may be caused by a number of conditions, including skin pathologies (i.e. stump edema, 
verrucose hyperplasia, epidermoid inclusion cysts, contact dermatitis, Marjolin’s ulcers, 
squamous cell carcinoma), positive pressure areas from a poor socket fit, bony nociceptive pain,  
adventitial bursitis, and neuroma formation15. Neuromas may form as early 6-10 weeks after 
nerve transection and are thought to produce ectopic neural discharges resulting in severe 
residual limb pain 16,17. A diagnostic block can help isolate a neuroma as the source of pain15.  
 
Evidence suggests that RLP and PLP commonly co-occur, and patients may struggle to 
differentiate these pain types18. Risk factors for these painful conditions include female sex, pre-
amputation pain, longer duration of time since amputation, residual pain in the still-intact 
contralateral limb, and upper extremity amputation10,19.  
 
Current treatments of PLP and RLP are often inadequate for controlling patients’ symptoms. In 
addition to significant pain and disability, individuals with PLP and RLP also experience a 
higher incidence of indecisiveness, suicidal ideation, and thoughts of self-harm compared to 
pain-free health survey participants8,20. Treatments include pre-operative analgesia, mirror 
therapy 13,21-23, guided motor imagery 21,23,24, acupuncture25, medications such as tricyclic 
antidepressants (TCAs) 26-28, selective serotonin reuptake inhibitors (SSRIs) 26, gabapentinoids 
26,29,30, sodium channel blockers27, ketamine26, opioids 27, and non-steroidal anti-inflammatories 
drugs (NSAIDs)5, transcranial magnetic stimulation 31, radiofrequency neurotomy32, 
cryoablation33, and neuromodulation (deep brain stimulation 35, dorsal root ganglion 
stimulation34, spinal cord stimulation35 and percutaneous peripheral nerve stimulation3). 
Additionally, various agents have been injected into and/or in close proximity to neuromas in 
attempt to mitigate pain symptoms, including local anesthetic 36, phenol37, alcohol38, and 
botulinum toxin36. In general, these treatments have been associated with modest outcomes at 
best. 
 
Pain improvement following mirror therapy suggests that the contralateral (intact) limb has an 
important role in PLP, and possibly RLP, resolution. This was further demonstrated in a 
randomized control trial39 that compared anesthetic and saline trigger point injections in 
participants’ intact limb (contralateral to the residual limb that experienced PLP). Contralateral 


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limb anesthetic trigger points provided greater pain relief than placebo, supporting the 
exploration of contralateral limb interventions to reduce PLP. An animal study established the 
pathophysiologic basis for this via the crossed-withdraw reflex40. 
 
The crossed-withdraw reflex occurs when an individual withdraws a limb with an injured nerve 
after a stimulus is applied to the contralaterally equivalent healthy nerve (i.e., right and left 
median nerve). Animal studies have proposed the following reflex mechanism: activated dorsal 
horn neurons on the uninjured side either directly, or indirectly, activate ventral horn neurons on 
the injured side40. This phenomenon occurs within 2 weeks of nerve injury and is likely due to 
plastic changes in the spinal cord. Furthermore, it appears that an injured nerve generates a 
greater proportion of wide-dynamic range (WDR) neuron activation on the contralateral limb 
nerve, when compared to contralateral WDR activation with two intact limb nerves41. This forms 
the basis for the current understanding of central nervous system changes following amputation 
that may contribute to PLP/RLP. 
 
While studies have evaluated ipsilateral sciatic nerve block for PLP, myofascial injections in the 
contralateral (intact) limb, and transcutaneous electric nerve stimulation (TENS) in the 
contralateral limb, no study to date has evaluated the efficacy of contralateral limb sciatic nerve 
block for the treatment of PLP/RLP32,39,40. The present study aims to define the attributable 
effects of contralateral sciatic nerve block on pain and function in participants with post-
amputation PLP/RLP.  
 
We hypothesize that contralateral sciatic nerve block with 2% lidocaine will demonstrate 
superior clinical pain outcomes compared to sham in PLP/RLP. If this hypothesis proves correct, 
the study findings would fundamentally change the limb loss pain treatment paradigm. This 
would allow clinical teams to pursue more advanced contralateral procedures including 
perineural steroid injection and peripheral nerve stimulation. This could improve physical and 
psychological function, quality of life, and reduce overall healthcare utilization and cost in a 
substantial portion of the limb loss population.  
 
We also believe that previous exploration into the basic science of the crossed-withdraw reflex 
and WDR neuron activity requires further validation with human subjects and clinical scenarios. 
A better understanding of this area will directly inform limb loss, pain, spinal cord, and 
neurology research.  
 
STUDY ENDPOINTS: 
Primary Outcome 
Comparison of the proportions of participants reporting ≥ 50% improvement in NRS pain score 
from baseline at 15 minutes in treatment and sham groups 
 
Secondary Outcomes (between and within-group comparisons will be used for each outcome): 
1) Mean and standard deviation (SD) of change in NRS pain score at 1, 2, 3, 4, 5, 6, 24, 48, 72, 
96, 120 hours post-saline and lidocaine injections  
2) Mean and SD of average daily steps recorded at 24, 48, 72, 96, 120 hours post-saline and 
lidocaine injections (via Modus StepWatch™ or Evolution EvoWalk™)  


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3) Mean and SD of change in Orthotics and Prosthetics User's Survey (OPUS) score immediately 
post-injection and conclusion of washout (5 days) in saline and lidocaine groups  
4) Mean and SD of change in Groningen Activity Restriction Scale (GARS) score immediately 
post-injection and conclusion of washout (5 days) in saline and lidocaine groups 
5) General linear model analysis of the interaction between crossover sequence  
6) Demographic factors associated with large improvement in NRS pain score  
7) Complications associated with the procedures 
 
STUDY INTERVENTION(S) / INVESTIGATIONAL AGENT(S): 
Image guided injection of the sciatic nerves with 2% lidocaine, 10 mL  
vs.  
Image guided injection of the sciatic nerves with preservative-free saline, 10 mL 
 
IND exemption criteria for 2% lidocaine: 
 The drug is lawfully marketed in the United States: Yes, 2% lidocaine is used as a 
standard local anesthetic in many medical offices throughout the United States. 
 The research is not intended to be reported to the FDA as a well-controlled study in 
support of a new indication for use nor intended to be used to support any other 
significant change in the labeling for the drug: Correct, our study is not evaluating the 
efficacy of lidocaine. Rather, it is evaluating a procedural technique that requires 
analgesia. Analgesia is well established property of 2% lidocaine.  
 The research is not intended to support a significant change in the advertising for the 
product: Correct. Lidocaine will be used to deliver analgesia. This is not a novel 
application of this medication.  
 The research does not involve a route of administration or dosage level or use in a patient 
population or other factor that significantly increases the risks (or decreases the 
acceptability of the risks) associated with the use of the drug product: Correct, we will be 
using a volume and concentration that is well within standard sodium channel blocker 
safety limits. Furthermore, we will use ultrasound guidance to deliver the medicine and 
effectively avoid intravascular administration of the medication, further reducing its risk.  
 The research is conducted in compliance with the marketing limitation described in 21 
CFR §312.7: Correct, we will not be promoting an investigational new drug in this study. 
Rather, we will be using a drug with well-established analgesic properties in a novel 
procedural technique.  
 
PROCEDURES INVOLVED: 
Study Design  
We aim to conduct a single-site, prospective, randomized, triple blind, sham-controlled, cross-
over trial of consecutive participants.to determine the efficacy of contralateral sciatic nerve block 
in treating chronic, refractory PLP/RLP. 
 
Figure 1: Study Crossover Design 
 


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Methods  
Twenty participants will be recruited from the Northwestern-affiliated practices of the PI and the 
Co-I, the Shirley Ryan Ability Lab, the University of Chicago, and local prosthetic clinics.  
 
Pre-visit: Candidates will be screened by authorized research personnel via chart review to 
determine candidacy for the study. If the participant meets eligibility criteria, they will be 
scheduled for a clinic visit. 
 
Visit 1 – Consent, inclusion screening, and prosthetic step counter placement 
All participants will present to the Pain Clinic (259 E. Erie, Suite 1400, Lavin Pavilion) and 
undergo an informed consent process with authorized research personnel. Eligibility criteria will 
be reviewed and confirmed. Dr. Walega will meet with the participant, explain the treatment 
block procedure, will review the medical history and perform a brief physical examination 
(focusing on residual limb point of maximal tenderness, review of prior imaging studies if 
available, and lower extremity musculoskeletal examination). Participants will provide baseline 
outcome measures and demographic data. Participants will be asked to complete the OPUS and 
GARS survey and provide demographic information. They will be given the option of 
completing these either on paper or on an iPad. 
 
Devices 
During initial evaluation (visit 1), participants’ prostheses will be fit with a Modus StepWatch™ 
or Evolution EvoWalk™. This will be tested in clinic by a research coordinator to ensure proper 
step count. The device will remain on participant’s prosthesis until study completion. Participant 
kinematic and gait data will be recorded by Modus StepWatch™ or Evolution EvoWalk™ and 
uploaded via Bluetooth to secure a de-identified, Health Insurance Portability and Accountability 
Act (HIPAA) compliant cloud-based storage application and extracted by research coordinator to 
an encrypted, HIPAA-compliant, Northwestern research database (REDCap). 
 
Participants will also be instructed to maintain a daily pain log through My Pain Diary 
smartphone application or paper log depending on participant preference. They will be asked to 
log daily pain scores during their treatment. Data will be extracted by a researcher to an 
encrypted, HIPAA-compliant, Northwestern research database (REDCap). 
 
Visit 2 (procedure 1)– Randomization and Study Intervention  


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Eligible participants will return to the Lavin 14th floor Pain clinic within 2 weeks of the initial 
visit. Participants will be randomized to treatment or sham group. Participant pre-procedure 1 
NRS pain score will be collected. Individual pain log will start 15 minutes after procedure. 
Participant will log pain score every hour until asleep. The next day, participant will record daily 
NRS pain score for 5 days. 
 
Randomization  
A computer-generated 1:1 block randomization scheme (https:// www.randomizer.org) will be 
used to assign participants to receive a peri-sciatic nerve injection with either 10 mL of 2% 
lidocaine or 10 mL of preservative-free saline (compounded by the 11th floor Lavin pharmacy 
and labeled with a “1” or “2” to ensure adequate blinding). Randomization will be performed by 
a research assistant by opening an opaque envelope to reveal the participant number and group 
assignment printed inside of the envelope. This will instruct authorized study personnel to draw 
up either 2% lidocaine or saline (labeled “1” or “2” by compounding pharmacy per above). The 
blinded injectionist will be provided an unlabeled syringe of injectate immediately before the 
injection procedure. Participants, injectionist, and study personnel who collect outcomes data 
will be blinded to group assignment. 
. 
 
Treatment block of sciatic nerve in contralateral limb: Procedure planning will be based on the 
participant’s indication of residual limb point of maximal pain (measured by distance from 
posterior superior iliac spine (PSIS) to most painful point [in cm]). Note that this point may 
beyond the anatomic end of the residual limb. The block will be performed at the exact same 
distance from PSIS on the contralateral side. If the block cannot be performed at this site due to 
anatomic or technical considerations (such as proximity to vascular structures), a more cephalad 
site along the sciatic nerve course will be selected for the procedure. During the block procedure, 
the participant will be positioned prone. Standard American Society of Anesthesiologists (ASA) 
procedure monitoring will be used (pulse oximetry, ECG, blood pressure, and heart rate). The 
participant’s skin will be prepared with chlorhexidine. A sterile ultrasound probe will be placed 
on the participants’ residual limb at a transverse angle in order to view the nerve in short-axis. 
The skin will be anesthetized with 1-2 mL of 1.0% lidocaine. The ultrasound probe (in plane) 
will be advanced to the intact limb’s sciatic nerve equidistance to that of the residual limb point 
of maximal pain. A 22-gauge standard echogenic needle will be placed adjacent to the sciatic 
nerve with ultrasound guidance. At the site of the nerve, 10mL of 2% lidocaine will be injected 
through the needle in the intervention group and 10ml of saline will be injected in the sham 
group.  
 
In treatment group: At the site of the nerve, 10mL of 2% lidocaine will be injected through the 
needle  
 
In control group: At the site of the nerve, 10ml of saline will be injected through the needle  
 
Following injection, participants will be kept in recovery area and monitored for 30 minutes. 
They will also complete a pain log starting 15 minutes post-injection. After the first pain score is 
recorded, the participants will dress and exit procedure area. Participants will be required to 
arrange transportation as the block may impair lower extremity motor function. 


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Both saline and local anesthetic will be administered to all subjects with a crossover design as 
described above. Participants will undergo 5-day washout between injections. 
 
Visit 3 – Crossover for both groups 
Eligible participants will return to the Lavin 14th floor Pain clinic within 5 days of visit 2. 
Participant pre-procedure 2 NRS and OPUS will be collected. Note that this will serve as post-
procedure 1 washout and pre-procedure 2 intervention data point.  
 
Both groups: will cross over and undergo treatment as described in Visit 2. Participant pain log 
will start 15 minutes after procedure 2. Participant will log pain scores every hour until asleep. 
The next day, participant will record daily NRS pain score for 5 days.  
  
Telephone call 1,2,3: participant will be called at 1- and 5-days post-procedures for NRS, OPUS 
survey and safety monitoring by research coordinator (see Safety Monitoring below). 
 
SAFETY MONITORING Participants will be contacted one day following both interventions to 
assess for any adverse events or side effects. 
 
DATA  
We will obtain socio-demographic and clinical variables:  
 Age (years) 
 Sex 
 Height (cm) 
 Weight (kg) 
 Level and side of amputation 
 Duration of pain (weeks) 
 Date of amputation 
 Etiology of amputation 
 Baseline NRS score for both PLP/RLP (worst, least, average, current) 
 Site of residual limb maximal pain (measured by distance from posterior superior 
iliac spine (PSIS) to most painful point [in cm]) 
 Analgesic medication log: dose and frequency of each medication participant 
currently taking 
 OPUS: Lower-Extremity Functional Status Measure Subsection Score 
 GARS 
 
POWER ANALYSIS  
Power and sample size calculations for this clinical trial were performed based on the data 
from a small cross-over study (N = 8) by Casale et al39. The primary outcome variable will 
be achievability of ≥ 50% pain relief (dichotomous variable with yes/no), calculated from 
pre- and post-inject NRS in each of the lidocaine and sham conditions (i.e., pre-injection 
NRS – post-injection NRS). Based on the data from Casale et al., along with our expected, 
overall success rate of 75% by lidocaine injection, we calculated the difference in two 
proportions of discordant pairs to be 0.625 and the overall proportion of discordant pairs to 
be 0.875. Using these values and binomial enumeration (1,500 enumerations), along with an 


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alpha level of 0.05, a power of 0.80, a two-sided t-test, and a dropout rate of 10%, the 
sample size was estimated as 20.  
 
STATISTICAL PLAN 
Data for the primary outcome variable, proportion of participants reporting ≥ 50% immediate 
pain reduction from baseline, will be reported as the mean and standard deviation (or median and 
interquartile range if not normally distributed) of the lidocaine and sham groups. Mean change in 
pain score, will be examined using an unpaired t test (NCSS) (or Mann-Whitney U test if not 
normally distributed). The median difference and its 95% CI will be calculated. The criterion for 
rejection of the null hypothesis will be P < 0.05.  
 
Participant data and secondary variables that are characterized by nominal data will be 
summarized as the number of participants in each category and the percentage of all participants 
in the group that they represent. These variables will be compared between the groups using the 
Pearson χ2 test, or when at least one of the cells of the contingency table had an expected 
number less than five, the Fischer exact probability test. The Miettinen-Nurminem score will be 
used to calculate 95% CIs for differences in percentages where indicated.  
 
Variables that are characterized by ordinal data and non-normally distributed continuous data 
(e.g., procedure time) will be summarized as median and interquartile range. These variables will 
be compared between the groups using the Mann-Whitney U test. Median differences and their 
95% CIs will be calculated where indicated.  
 
Variables that are characterized by normally distributed continuous data (e.g., age and body 
weight) will be summarized as mean and standard deviation. These variables will be compared 
between the groups using the unpaired t test (NCSS). Mean differences and their 95% CIs will be 
determined.  
 
In case there were significant differences in the demographic variables, multivariate logistic and 
linear regression analyzes will be conducted to examine the binary and continuous outcome 
variables by group, while accounting for the statistically significant demographic variables 
analysis will be used to determine if any demographic or clinical variables (age, BMI, duration 
of pain, etc.) are independently associated with successful pain (NRS) outcomes. 
 
Lastly, Pearson’s correlation coefficients will be computed to assess the relationships among 
various demographic and procedural covariates. 
 
 
 
 
 
 
 
 
 
 


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DATA AND SPECIMEN BANKING 
NA 
 
SHARING RESULTS WITH PARTICIPANTS 
Results will not be shared with participants or their medical providers. 
 
STUDY TIMELINES 
 IRB submission and approval process: 2 months  
 Recruitment: 12 months  
 Statistical analysis and manuscript: 2 months  
 Duration of participation for each participant is approximately: 3 weeks 
 
INCLUSION AND EXCLUSION CRITERIA 
INCLUSION CRITERIA 
1. Age greater than 18 years of age at day of enrollment 
2. Lower extremity amputation performed more than 12 months before study enrollment 
3. PLP/RLP in affected amputated limb > 4 on NRS26 
4. Pain duration of more than 6 months despite a trial of conservative therapies for at least 2 
months, including oral medications, topical medicines, physical therapy, and physical 
modalities (i.e., heat, cold, transcutaneous electrical nerve stimulation, phonophoresis)  
5. Willingness to undergo image guided diagnostic nerve block 
 
EXCLUSION CRITERIA  
1. Refusal / inability to participate or provide consent 
2. Contraindications to diagnostic nerve block 
3. Non-neurogenic source of PLP/RLP 
4. Current opioid use > 50 morphine milligram equivalents per day 
5. Any interventional pain treatment in the residual limb within the last 30 days 
6. Severe uncontrolled medical condition (i.e., hypertensive crisis, decompensated 
hypothyroidism) 
7. Use of investigational pain drug within past 30 days or other concurrent clinical trial 
enrollment 
 
VULNERABLE POPULATIONS 
NA 
 
PARTICIPANT POPULATION(S) 
Accrual 
Number: 
Category/Group: 
(Adults/Children 
Special/Vulnerable 
Populations) 
Consented: 
Maximum Number to be 
Consented or 
Reviewed/Collected/Screened 
Enrolled: 
Number to Complete 
the Study or Needed 
to Address the 
Research Question 
Total: 
1 Adult Group 
20 
20 
 
 
 


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RECRUITMENT METHODS 
Participants will be recruited from the Northwestern-affiliated practices of the PI, the Shirley 
Ryan Ability Lab, the University of Chicago, and local prosthetic clinics. The trial will be posted 
on clinicaltrials.gov. IRB approved flyers will also be used. 
 
COMPENSATION FOR PARTICIPATION IN RESEARCH ACTIVITIES 
None 
 
WITHDRAWAL OF PARTICIPANTS 
Participants may withdraw from the study at any time. Participants may be withdrawn from the 
research without their consent if they are non-compliant with providing outcome measures or 
study visits. 
 
RISKS TO PARTICIPANTS 
Ultrasound-guided perineural anesthetic injection is a commonly performed procedure in the 
U.S. and is considered safe and effective in treating chronic pain. It is considered very safe when 
performed with image guidance and by an experienced injectionist. The major complication 
(permeant nerve injury) rate following peripheral nerve block is estimated to be 1.5 / 10,00042. 
 
RISKS RELATED TO NEEDLE PLACEMENT  
- Temporary bruising or swelling at the site of the injection  
- Hematoma (pocket of blood caused by bleeding from a broken blood vessel)  
- Infection of the tissues of the leg surrounding the area of injection  
 
RISKS RELATED TO INJECTION OF MEDICATIONS  
Lidocaine Risks 
 Infrequent 
- Bradycardia 
- Hypotension 
- Drowsiness 
- Dizziness 
- Muscle twitching 
- Nervousness 
- Paresthesia 
- Sensation of feeling cold 
- Anxiousness 
 Rare 
- Allergic reaction to lidocaine  
- Skin injury including ulceration at the site of the injection  
- Methemoglobinemia 
- Diplopia 
- Cardiac manifestations: Bradycardia, tachycardia, ventricular tachycardia, ventricular 
fibrillation, asystole, wide / premature QRS, bundle branch block, II to III AV block, ST 
changes, ventricular ectopy 
- Respiratory depression 
- Unconsciousness 


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- Seizure 
- Nausea 
- Apprehension 
 
Normal Saline Risks 
- Hypernatremia 
 
Loss of confidentiality  
 
 
POTENTIAL BENEFITS TO PARTICIPANTS 
Individual participants may experience short- or long-term improvements in pain as a result of 
participation in this research. 
 
DATA MANAGEMENT AND CONFIDENTIALITY 
All data will be de-identified and recorded in duplicate on electronic study-specific case report 
forms (CRFs). Data will be entered utilizing REDCap. Participants will be given a study 
identification number that will be reported on all CRFs and source documents. Only the PI and 
authorized staff, according to the list of Authorized Study Personnel, are entitled to make entries 
on the CRF. Personal participant data will be kept confidential. Participant documentation will 
identify a participant by initials and study number. Only the PI will keep in his file a Participant 
Identification and Enrollment List. To allow compliance with GCP principles, each participant 
will be asked for consent regarding the access to source documents for monitoring, audits, and 
inspections. Data both electronic and paper will be destroyed 5 years after manuscript 
completion using current vendors and department protocol. Paper documents will be stored in the 
Arkes 10th floor Anesthesiology Administrative Office which is key card controlled in a locked 
research closet. 
 
PROVISIONS TO MONITOR THE DATA TO ENSURE THE SAFETY OF 
PARTICIPANTS 
A data safety monitoring board consisting of the Department of Anesthesiology Director of 
Research, a pain medicine attending physician, a statistician, and study research personnel will 
periodically evaluate the data collected to determine whether participants remain safe. Safety 
data and adverse event data will be reviewed using the medical record and data collection form. 
It will be reviewed every 10 subjects or if one of the study subjects experiences a rapid response 
team intervention. Data will be compared between groups using the χ2 statistic or the Fisher’s 
exact test. A p-value < 0.05 will be required to reject the null hypothesis. 
 
PROVISIONS TO PROTECT THE PRIVACY INTERESTS OF PARTICIPANTS 
Data will be de-identified and given a study identification number. The PI will keep in his file a 
subject identifier log. To allow compliance with GCP principles, each participant will be asked 
for consent regarding the access to source documents for monitoring, audits, and inspections. 
During the consent process they will be reassured that their data will be de-identified and 
personal participant data will be kept confidential. 
 
COMPENSATION FOR RESEARCH-RELATED INJURY 


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None 
 
ECONOMIC BURDEN TO PARTICIPANTS 
The patient will not be responsible for these healthcare services or medications. 
CONSENT PROCESS 
Participants will be consented in the NMH Pain Clinic (259 East Erie Street, Suite 1400) by 
authorized research staff. Authorized research staff will explain the consent document. Each 
section of the form will be discussed, taking time to highlight the purpose of the study, 
procedures, risks, confidentiality measures taken to protect the participant, and how to 
revoke/withdraw consent, if desired, and to answer any questions the participate may have. They 
will also be informed that participation in this study is completely optional and regardless of 
their participation their care will not be negatively impacted. Subjects will be given ample time 
as they need to make their decision. The participants will receive a signed copy of the consent. 
 
NON-ENGLISH SPEAKING PARTICIPANTS  
NA 
 
 
WAIVER OR ALTERATION OF CONSENT PROCESS  
NA 
 
PROTECTED HEALTH INFORMATION (PHI AND HIPAA) 
HIPPA Authorization will be obtained from all research subjects through the consent document. 
Subjects will give us the permission to use personal health information that includes health 
information in the medical records and information that can identify them. Personal health 
information may include the subjects name, address, or phone number. Health information we 
collect and use for this research includes:  
 
• All information in a medical record  
• Results of physical examinations  
• Medical history  
• Lab tests, or certain health information indicating or relating to a particular condition as well as 
diaries and questionnaires  
• Records about study medication or drugs  
• Records about study devices 
 
QUALIFICATIONS TO CONDUCT RESEARCH AND RESOURCES AVAILABLE 
There is a large volume of chronic pain patients treated annually at NMH, ensuring the 
participant sample projections can be achieved. In addition, a co-investigator serve as faculty at 
the Shirley Ryan AbilityLab, the nation’s largest amputee rehabilitation program. The principal 
investigator has 22 years of clinical experience performing ultrasound-guided nerve blocks in 
both a clinical and research setting. He has authored several peer reviewed articles on the topic 
of perineural injections for pain indications.  
 
All research team members have completed the necessary regulatory training. We anticipate 1-2 
cases per week. Authorized research personnel will have dedicated time to recruit participants. 
All authorized research personnel are informed about the protocol and their duties and functions. 


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MULTI-SITE RESEARCH 
This is a single-site study 
 
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