Clinical trial NCT05501600
Conditions: Anesthesia Pain
Keywords: lidocaine functional MRI electric nerve stimulation functional connectivity
Sponsor: Keith M Vogt
Start date: 2022-11-22; Completion date: 2023-11-17
Enrollment: 30 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to characterize the effects of intravenous lidocaine on pain processing and cognitive function. Functional magnetic resonance imaging will be used to identify the neural correlates of these phenomena. The study will consist of 1 visit and involves no long-term follow up.

Detailed description:
This is an observational cohort study of volunteer subjects, which will employ neuroimaging and behavioral measures to characterize the effects of intravenous lidocaine on pain processing and cognitive function. A steady-state effect-site concentration of lidocaine will be achieved, and a short battery of cognitive behavioral tasks will be employed. At the dose target, pain task functional MRI and resting-state connectivity will be determined. This work will use a systems neuroscience approach to fill an important knowledge gap about the central effects of intravenous lidocaine, a commonly-used opioid alternative analgesic agent.

Aim1: Determine cognitive behavioral effects of a steady-state dose of IV lidocaine using a short battery of tasks. The investigators hypothesize that the administration of lidocaine will correlate to decreased pain ratings, slowed psychomotor response, and decreased memory encoding.

Aim2: Determine the neural effects of a steady-state dose of IV lidocaine in response to acute pain, and on resting connectivity. The investigators hypothesize that pain task-related activation will decrease in the insula and anterior cingulate, corresponding to decreased ratings of pain intensity and unpleasantness. Additionally, the investigators expect widespread decreases in long-range functional connectivity between brain areas know to be involved in these two areas and other known to be involved in pain processing.

Arms: arm 1: Subjects will receive lidocaine during the drug portion of the experiment.
Interventions: intervention 1: Peripheral Nerve Stimulation intervention 2: Lidocaine IV
Intervention descriptions: intervention 1: Experimental acute pain stimulus will be delivered using an electric nerve stimulator. intervention 2: Subjects will receive an intravenous infusion of lidocaine for about 30 minutes.

Protocol documents:
ICF_000.pdf: 
ClinicalTrials.gov 
Document cover page 
Official Title: Neural Correlates of Lidocaine Analgesia 
ClinicalTrials.gov ID (NCT number): NCT05501600 
Document Date: 6/20/2023 


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CONSENT TO ACT AS A Study Title:  Neural Correlates of Lidocaine Analgesia
PARTICIPANT IN A RESEARCH STUDY
KEY INFORMATION 
1. You are being offered the opportunity to participate in a research study.  One of the
investigators will explain the study to you and will answer any questions you might have.  You
should take your time to make your decision, which is completely voluntary.
2A. Summary of the research
Purpose of the research: The purpose of this study is to better understand how IV lidocaine 
acts in the brain to affect pain perception. 
Duration, number of study visits: There is one visit associated with participation in this study. 
This visit will last approximately 3 hours.  
Overview of study procedures: 
•
urine pregnancy screen (for females)
•
nerve stimulator calibration to a pain intensity of 7/10
•
brief physical exam including listening to your lungs and heart and looking at/in your
neck and mouth; you will be weighed.
•
questions about medical conditions, past surgeries, medications, allergies, any
symptoms that you have during physical activity, and your weight. If you do not have a
scale and are unable to locate one to use, give us your best estimate of your weight
and we will weigh you on arrival to confirm.
•
Two intravenous (IV) catheter placements (using needles)
•
IV lidocaine infusion
•
Blood draw through IV catheter (two 5mL tubes collected)
•
MRI safety screening questions
•
enter the high magnetic field environment of the MRI scanner
•
connection to monitor that measures your heart rate, blood pressure, and breathing
•
placement inside the MRI scanner
•
experience painful stimulation while being scanned by the MRI
•
Recovery from the drug, until thinking and feeling normally
3. Reasonable, foreseeable risks or discomforts
UPMC |
University of Pittsburgh
Medical Center
Department of Anesthesiology & Perioperative Medicine


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Risks and side effects related to the MRI scanning include those which are: 
Likely: Discomfort from loud noise, positional discomfort
Rare but serious:  claustrophobia, risk of interaction with undetected/undisclosed metal 
in/on subject's body that could cause physical injury; hearing damage/loss 
Risks and side effects related to the collection & storage of personal health information 
include those which are: 
Rare but serious: Breach of confidentiality
Risks and side effects related to the electric nerve stimulation include those which are: 
Likely: Pain due to electric shock
Rare but serious: Theoretical risk of burns due to an interaction with MRI scanner
Risks and side effects related to the lidocaine administration include those which are:
Likely: sedation, abnormal taste
Less Likely: burning on injection, confusion, hearing abnormal sounds (ringing in ears)
Rare but serious: allergic reaction, seizures, abnormal heart rhythm
Risks and side effects related to IV access include those which are: 
Likely: Discomfort or pain, bleeding or bruising, skin sensitivity
Less likely: possibility of multiple needle punctures
Rare but serious: infection, blood clot
Risks and side effects related to blood draw include those which are: 
Likely: Discomfort or pain, bleeding or bruising, skin sensitivity
 Rare but serious: infection
Risks and side effects related to the pre-visit restrictions include those which are: 
Less Likely: Discomfort from hunger or strong urge to urinate
4. Reasonable, expected benefits
You will be compensated $150 for participation. There are otherwise no direct benefits
to you from participating in the study.  However, this study will help the researchers
learn more about how the commonly-used mediation lidocaine changes the experience
of pain.


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CONSENT TO ACT AS A PARTICIPANT IN A RESEARCH STUDY
TITLE:  Neural Correlates of Lidocaine Analgesia
CO-INVESTIGATOR:
PRINCIPAL INVESTIGATOR:
Keith M. Vogt, MD, PhD
Anesthesiology & Perioperative Medicine
Montefiore Hospital, Suite 467
3459 Fifth Avenue, Pittsburgh, PA  15213
SOURCES OF SUPPORT:
Department of Anesthesiology & Perioperative Medicine, University of Pittsburgh, 
School of Medicine
National Institutes of General Medical Service
Why is this research being done?
You are being offered the opportunity to take part in a research study.  Research 
Studies include only people who choose to take part.  The study team members will 
explain the study to you and will answer any questions you might have.  You should 
take your time to make your decision. The purpose of this study is to better understand 
what happens in the brain when people receiving intravenous (IV) lidocaine and 
experiencing pain. 
Who is being asked to take part in this research study?
Any adult under 70 years old who is not pregnant, free from any serious chronic medical 
condition, has never had a history of psychological or neurological disease, and who 
has never had a reaction to lidocaine may be able to participate in this study. 
To re-iterate, specific exclusion criteria include:
-
being pregnant or attempting to conceive
-
having a body mass index (BMI) greater than 40
-
being older than 70 years old
-
having moderate to severe sleep apnea
-
having chronic pain requiring the use of pain medicine 3 or more times per week
-
having neurologic or psychiatric disease, including benign tremor, anxiety, and
depression
-
having history of cardiac rhythm disturbance (such as heart block, or atrial
fibrillation)
-
having history of seizures
-
being severely claustrophobic
-
have metal implants or non-removable metal piercings
James W. Ibinson, MD, PhD
Anesthesiology & Perioperative 
Medicine


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-
having metal-containing tattoos, particularly on the face
-
having a history of adverse reaction to lidocaine or to any other local anesthetics 
of the amide type
-
regularly taking: antiepileptics, antidepressants, anti-psychotics, anti-anxiety 
medication, stimulants, sleep-aids, or pain medication
-
having Wolff-Parkinson-White syndrome
-
having known renal or hepatic dysfunction
-
having glucose-6-phosphate dehydrogenase deficiency or history of 
methemoglobinemia
We will recruit 30 people to participate. The total time for you to participate is 2-3 hours 
over 1 visit.
What procedures will be performed for research purposes?
There is one visit associated with participation in this study. This visit will last 
approximately 3 hours. The MRI scanners that will be used for this project are located 
within the two Magnetic Resonance Research Center facilities, either the 8th floor B-
wing 3T scanners or the 7T scanner in the basement of the Biomedical Science Tower 
3 (a research facility connected by bridge to UPMC Presbyterian/Montefiore). The 
scanner to be used would be determined in advance for a subject cohort, and you would 
be informed in advance of the research location.
If you decide to take part in this research study, you will undergo the following 
procedures:
Experimental Procedures:
If you qualify to take part in this research study, you will undergo the experimental 
procedures listed below,  
1. We will ask you to abstain from solid food and caffeine for 8 hours prior to your 
scheduled visit, consume only clear liquids until 1 hour prior to your scheduled 
arrival time, and not urinate in the hour before the visit (if a urine sample is 
needed).
2. We will collect a urine sample to test for pregnancy from female subjects. 
3. We will measure your weight.
4. A nerve stimulator will be connected to one or two of your fingers with two small 
electrodes. A small electrical current will then be delivered. Starting at zero, the 
intensity will slowly be increased until you report a pain of 7 out of 10, where 0 is 
no pain and 10 is intolerable pain. The nerve stimulator will then be turned off 
and then used periodically for a few seconds at a time during the rest of the 
experiment. Unless you request an adjustment, the level of current delivered 
(pain intensity) will not be changed after adjustment to the level you rate as 7 out 


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of 10 pain. 
This study uses low doses of intravenous lidocaine. This drug is used routinely to 
relieve pain in patients, for example before, during, or after surgery. A physician 
anesthesiologist will interview you and do a brief physical exam to be sure you 
are safe to receive lidocaine. These will include (at least) questions about your 
medical conditions, past surgeries, medications, allergies, and any symptoms 
that you have during physical activity. The examination will consist of (at least) 
looking in your mouth, feeling your neck, and listening to your heart and lungs 
with a stethoscope.
Two intravenous needles (IV) will be placed, likely in your hand or arm and foot. 
The needles are removed, and small plastic catheters (tube) will remain in your 
body throughout the study.  One IV will be used to give you fluid and the 
lidocaine used in the study. The other will be used to obtain a blood sample 
during the scan. This blood sample collection will consist of two 5mL tubes which 
is about ½ teaspoon of blood. You will also be connected to vital sign monitors, 
to measure your heart rate, blood pressure, and breathing. These procedures will 
take approximately 15 minutes.
You will receive both IV fluid (a saltwater solution) and lidocaine at the visit.  For 
this study, the drug is administered by a physician anesthesiologist (a doctor with 
specialized training in the administration of these medications). 
5. You will be asked additional screening questions to ensure that it is safe for you
to undergo MRI scanning (no metal or electronic implants, no metal-containing
tattoos, etc). Prior to entering the MRI environment, you will be asked to remove
any jewelry or glasses and be asked to change into a hospital gown if your
clothes contain any metal.
6. You will receive lidocaine and a medical saltwater solution (IV fluid) through your
IV, which will take 10-15 minutes to reach effect. You will experience periodic
brief painful stimulation, as described above. A qualified anesthesia provider will
monitor your response to the medication at all times. This part of the study will
take about 60 minutes, after this you will have completed the experiment for this
visit.
7. You will then be monitored while you recover from the effects of sedation. Water
will be available, and a limited selection of study-provided snacks may be 
available.  But, you are encouraged to bring your own drink and snack to eat 
afterwards, if desired. Your IV line will be removed, and the study doctor will 
check with you to be sure you are feeling well. Once it is safe to do so, you will 
be discharged, typically 30 minutes later. You are not allowed to drive a vehicle 
or operate machinery after receiving lidocaine for the rest of the study visit day. 
You will need to arrange a way to get home or to your next destination (without 
driving) from the study visit. If you have any symptoms or concerns, please call 


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Dr. Vogt. You will be paid $150 for completing this study visit prior to your 
discharge.
What are the possible risks, side effects, and discomforts of this research study?
Performing the experimental tasks pose no risks to subjects. Other aspects of the study 
involve some risk, which are described below.  As with any experimental procedure, 
there may be adverse events or side effects that are currently unknown and some of 
these unknown risks could be permanent, severe or life-threatening.
Risks of Pre-Visit Restrictions 
There is a small risk of discomfort from the pre-visit restrictions, such as hunger and the 
urge to urinate. 
Risks related to intravenous (IV) access
•
Discomfort will occur in all subjects with needle insertion.
•
There is a risk of a small bruise or soreness at the IV site, that may last for
several days after the study.
•
Individuals with sensitive skin may experience some temporary irritation or skin
rash from the adhesive dressing or tape used to cover the puncture site.
•
Less than 1% risk of fainting (syncope), or nausea/vomiting with IV placement
•
IV infiltration (leaking out of the vein), in which case fluid would temporarily
accumulate in your arm. This would resolve spontaneously, though this situation
poses a very small risk of blood clot or tissue damage as a result.
•
Extremely small risk of serious bleeding or infection related to IV placement.
Study personnel who are trained in IV access will implement precautionary
measures including ensuring your physical comfort, proper disinfection of the
needle insertion site, application of pressure after removal of the needle, and
monitoring for any problems.
•
Some individuals have veins that are unexpectedly difficult to access, and these
subjects could experience multiple needle sticks in an attempt to obtain a
functioning IV.  As IV access is required for the study procedures, inability to
obtain IV access could result in involuntarily withdrawal from the study.
Risks related to IV blood sample collection:
•
Minor discomfort or bruising at the site of IV placement
•
In rare cases, blood collection may lead to infection.
Known risks of Receiving lidocaine:
Common side effects include: 
Sedation, abnormal taste, pain on injection
Uncommon possible side effects include:
Confusion, hearing abnormal sounds (ringing in ears), allergic reaction, seizures, 
abnormal heart rhythm


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Other risks of lidocaine administration:
Anxiety, depression, lightheadedness, dizziness, restlessness, feeling sleepy, 
drowsiness, nausea, dry mouth, headache, blurred/double vision, numb or tingling 
mouth, out of body sensations, ringing or buzzing of the ears, slowed or rapid heart rate, 
low blood pressure, slowed breathing, tremors (where your hands or a part of your body 
is shaky), seizures
Risks related to painful electric nerve stimulation
Because the effects of lidocaine on pain are being studied, pain will be repeatedly 
experienced in this study. Each occurrence of the pain will be brief, and you can have 
the painful stimulus (and the entire experiment) stopped at any time by notifying any 
research team member. Once electrical stimulation is stopped, there will be immediate 
pain relief.  
Risks of MRI scanning
•
You may feel nervous and/or claustrophobic during the MRI scans. 
•
While the MRI is running, you will be asked to lie still on a narrow bed inside of 
the scanner and the scanner will make a loud knocking or beeping sound. The 
noise level is within safety limits, but you will be asked to wear earplugs, since 
this noise is uncomfortable for some people. You will be in verbal contact with the 
investigators and operator of the MRI machine, and you can request that the 
experiment (and scanning) be stopped at any time, and you would be 
immediately removed from the scanner. 
•
During the scanning process, you are lying on your back, and it is possible that 
you may feel some discomfort related to positioning. 
•
There are no known long-lasting side effects from MRI scanning. 
If your clothing is uncomfortable, or contains metal, you will be asked to change (in a 
private dressing room) into a hospital gown prior to entering the MRI scanner.
Risks of Breach of Confidentiality
There is a potential risk of breach of confidentiality that is inherent in all research 
protocols. There is a possibility that if research data were to become known, this 
knowledge could potentially impact a subject's future or have a negative impact on 
family or social relationships.
With your permission, we will use text messaging and email to remind you of 
appointments and scheduling issues. No personal information will be transmitted; 
however, know that both email and text messages are NOT secure.
What are possible benefits from taking part in this study?
You will receive no direct benefit from taking part in this research study. Participation in 
this study will help further the understanding of how the brain forms memories when 
under sedation and experiencing pain.  


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If I agree to take part in this research study, will I be told of any new risks that 
may be found during the course of the study?
Although unlikely, you would be promptly notified if any new information develops during 
the course of this research study which suggests that you were put at any increased risk 
as a result of your participation.
Will my insurance provider or I be charged for the costs of any procedures 
performed as part of this research study?
Neither you, nor your insurance provider, will be charged for the costs of any of the 
procedures performed for the purpose of this research study (i.e., the Screening 
Procedures, Experimental Procedures, or Monitoring/Follow-up Procedures described 
above).  
Will I be paid if I take part in this research study?
You will be paid a total of $150 for completing the in-person visit and all associated 
procedures in the study.  This payment will be processed on a reloadable debit card.  
Since you are being compensated for your participation in this study, your name, 
address, date of birth, and social security number will be released to the Accounting 
Office. All compensation is taxable income to the participant regardless of the 
amount.  If you receive $600 or more in a calendar year from one organization, that 
organization is required by law to file a Form 1099 – Miscellaneous with the IRS and 
provide a copy to the taxpayer. Individuals who do not provide a social security number 
may still participate in the research, but the IRS requires that 24% of the payment be 
sent by the institution to the IRS for ‘backup withholding;’ thus you would only receive 
76% of the expected payment. 
Commercialization statement
Your data from this research study may contribute to a new discovery or treatment. In 
some instances, these discoveries or treatments may be of commercial value and may 
be sold, patented, or licensed by the investigators and the University of Pittsburgh for 
use in other research or the development of new products. You will not retain any 
property rights nor will you share in any money that the investigators, the University of 
Pittsburgh, or their agents may realize.
Who will pay if I am injured as a result of taking part in this study? 
If you believe that the research procedures have resulted in an injury to you, 
immediately contact the Principal Investigator who is listed on the first page of this form. 
Emergency medical treatment for injuries solely and directly related to your participation 
in this research study will be provided to you by the hospitals of UPMC. Your insurance 
provider may be billed for the costs of this emergency treatment, but none of those 
costs will be charged directly to you. If your research-related injury requires medical 
care beyond this emergency treatment, you will be responsible for the costs of this 
follow-up care. At this time, there is no plan for any additional financial compensation.  
You waive no legal rights by signing this consent form.


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What information will be collected about me and who will know about my 
participation in this research study?
We will not be reviewing your medical record information for the purposes of this study.  
However, we will collect information directly from you including: demographic 
information such as age, weight, and height; and portions of your medical history 
(including substance use history) necessary to determine your ability to safely undergo 
receive lidocaine and undergo MRI scanning. Representatives from the National 
Institutes of Health or the University of Pittsburgh Office of Research Protections may 
access identifiable private information for purposes of monitoring the study.
To protect your privacy, we will store this collected information separately from personal 
identifiers such as your name and contact information. Thus, your research data will 
only be identified by a code and not linked to you personally. Although we will do 
everything in our power to protect your privacy and the confidentiality of your records, 
just as with your medical information for health care purposes, we cannot guarantee the 
confidentiality of your research records. The identifiable link between your personal 
formation and your data will be stored for a minimum of 7 years after final reporting of 
study results, and then this link (your personal information) will be destroyed. All de-
identified data from this study will be kept securely for an indefinite period of time. No 
third party, including relatives, personal physicians, or insurance companies will be 
granted access to the identifiable information we collect. It is possible that we may 
share the information from this study, so that it may be combined with other data in 
larger future studies. However, your information would only be shared with other 
researchers without any personal identifiers, so no one would be able to learn your 
identity. For the purpose of monitoring the conduct of this study, authorized 
representatives from the University of Pittsburgh Office of Research Protections may 
review your research information.
For the purpose of monitoring the conduct of this study, authorized representatives from 
the University of Pittsburgh Office of Research Protections may review your research 
information. Additionally, an Independent Medical Monitor, Dr. Tetsuro Sakai, MD, PhD 
(who is a UPMC anesthesiologist not involved in conducting the study) will review the 
medical information (such as heart rate, blood pressure and reported adverse events) 
that are collected during the study. This data will be shared with the Independent 
Medical Monitor in de-identified format, such that your name and personal information is 
not linked to the medical information.
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health. The researchers with this Certificate may not disclose or use information, 
documents, or biospecimens that may identify you in any federal, state, or local civil, 
criminal, administrative, legislative, or other action, suit, or proceeding, or be used as 
evidence, for example, if there is a court subpoena, unless you have consented for this 
use. Information, documents, or biospecimens protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research except, if there is a 
federal, state, or local law that requires disclosure (such as to report child abuse or 


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communicable diseases but not for federal, state, or local civil, criminal, administrative, 
legislative, or other proceedings; if you have consented to the disclosure, including for 
your medical treatment; or if it is used for other scientific research, as allowed by federal 
regulations protecting research subjects.
A description of this clinical trial will be available on http://www.clinicaltrials.gov, as 
required by US Law. This website will not include information that can identify you. At 
most, the website will include a summary of the results. You can search this website at 
any time. 
Is my participation in this research study voluntary?
Yes! Your participation in this research study is completely voluntary. Whether or not 
you provide your consent for participation in this research study will have no effect on 
your current or future relationship with the investigators, the University of Pittsburgh, or 
UPMC. Your participation will not affect your current or future medical care at a UPMC 
hospital or affiliated health care provider or your current or future relationship with any 
healthcare insurance provider.
May I withdraw my consent for participation in this research study?
You may withdraw your consent for participation in this research study at any time.  Any 
identifiable research information recorded for, or resulting from, your participation in this 
research study prior to the date that you formally withdrew your consent may continue 
to be used and disclosed by the investigators for the purposes described above.
To withdraw your consent for participation in this research study, contact the principal 
investigator of this research study at the address/phone number listed on the first page 
of this form.
If I agree to take part in this research study, can I be removed from the study 
without my consent?
You may be removed from the study by the researchers if any practical considerations 
or safety concerns arise that do not allow you to participate.
Will clinically relevant results be available to me?
Any clinically-relevant abnormalities will be disclosed to you, at the discretion of one of 
the study physician investigators. The MRI scan is being done for research purposes. It 
may detect an unknown abnormality but cannot provide a diagnosis. The study team will 
advise you if follow-up care is recommended for any abnormal medical findings.


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****************************************************************************************************
VOLUNTARY CONSENT
The above information has been explained to me and my current questions have been 
answered.  I understand that I am encouraged to ask questions about any aspect of this 
research study during the course of this study, and that such future questions will be 
answered by a qualified individual or by the investigator(s) listed on the first page of this 
consent document at the telephone number(s) given. I understand that I may always 
request that my questions, concerns or complaints be addressed by a listed 
investigator.  
I understand that I may contact the Human Subjects Protection Advocate of the IRB 
Office, University of Pittsburgh (1-866-212-2668) to discuss problems, concerns, and 
questions; obtain information; offer input; or discuss situations that have occurred during 
my participation. By signing this form, I agree to participate in this research study and 
allow the use of my private health information. A copy of this consent form will be given 
to me.
__________________________ _____________________
____________
Participant’s Signature
Printed Name of Participant
Date
CERTIFICATION of INFORMED CONSENT
I certify that I have explained the nature and purpose of this research study to the 
above-named individual(s), and I have discussed the potential benefits and possible 
risks of study participation.  Any questions the individual(s) have about this study have 
been answered, and we will always be available to address future questions as they 
arise.
I further certify that no research component of this protocol was begun until after this 
consent form was signed.
___________________________________
________________________
Printed Name of Person Obtaining Consent
Role in Research Study
_________________________________
____________
Signature of Person Obtaining Consent
Date 

Prot_001.pdf: 
 
ClinicalTrials.gov Document cover page  
 
Official Title: Neural Correlates of Lidocaine Analgesia  
 
ClinicalTrials.gov ID (NCT number): NCT05501600  
 
Document Date: 6/20/2023 
 
 


Study Protocol 
Participants will be recruited from the community by several methods of advertising. 
Eligible subjects will be emailed a copy of the consent form, at least 24 hours to review 
the form.  If subjects express continued interest in enrolling in the study, they will 
continue to enrollment. 
A phone discussion with the PI will be scheduled, and consent will be completed in 
advance of the study visit, using real-time 2-way discussion over the phone and 
electronic capture of consent using RedCap. After consent, the subject will be 
scheduled for their study visit, and reminders sent by email/text at their preference.   
Subjects will be given instructions for several pre-visit restrictions.  1 - They will be 
asked to abstain from caffeine intake for 8 hours prior to their visit.  This ensures that 
the vasoconstrictive effects do not interfere with the blood flow response on which fMRI 
depends (avoiding an experimental confound). 2- The participant will avoid any solid 
food, fat, or protein intake for 8 hours prior to their visit. Subjects will also avoid clear 
liquids for 2 hours prior to the visit, for the same reason. This is to ensure their stomach 
is empty and to prevent a possible complication of regurgitation or aspiration, consistent 
with American Society of Anesthesiologists guidelines for preoperative oral intake.(1) 3 - 
Female subjects will be asked to not urinate in the hour before the visit, so that they are 
easily able to void on arrival, and a urine sample can obtained in a timely manner. 
Subjects will also be instructed on the post-visit restriction to not drive a vehicle or 
operate machinery immediately after receiving lidocaine.  They will be informed that 
they will need to arrange for a way to get home (without driving) from the study visit.   
On arrival, subjects will be met by a member of the study team in the BST3 lobby, and 
be escorted through the secure facility to the 7T research scanner in the basement.  
Urine sample will be obtained from female subjects (private bathroom is available), and 
pregnancy test will be performed on the sample.  Subjects will be informed of the result. 
A nerve stimulator (EZ Stim II, LifeTech; currently being used in STUDY19030183) will 
be connected to a finger with two small electrodes. A low amplitude electrical current 
will then be delivered. Starting at zero, the intensity will slowly be increased until they 
report a pain of 7 out of 10, where 0 is no pain and 10 is intolerable pain. The nerve 
stimulator will then be turned off and then used periodically for 10 seconds at a time 
during the subsequent portions of the experiment. Unless the subject requests an 
adjustment, the level of current delivered will not be changed after initial adjustment. 
A physician anesthesiologist will interview the subjects and do a brief physical exam to 
ensure it is safe to receive lidocaine. This will include questions about medical 
conditions, past surgeries, medications, allergies, and any active symptoms. The 
examination will consist of (at least) looking in the mouth and listening to the heart and 
lungs with a stethoscope. An intravenous (IV) catheter will be placed, likely in the hand 


or arm, and will remain in place throughout the study.  Baseline vital signs will be 
obtained. 
Subjects will be asked additional screening questions by the MRI scanner staff, per their 
protocol, to ensure that it is safe to undergo MRI scanning (no metal or electronic 
implants, no metal-containing tattoos, etc). Prior to entering the MRI environment, 
subjects will be asked to remove any jewelry, electronic, and glasses. In the unlikely 
event that their shirt contains metal, they will be provided a hospital gown and private 
space to change. 
Subjects will then enter the scanner room, receive ear plugs and be connected to vital 
sign monitors, to measure your heart rate, blood pressure, and breathing (expired 
carbon dioxide). They will be connected to the IV lines and the crystalloid IV carrier fluid 
infusion will begin.  From this point forward, regular vital signs will be obtained and 
documented, as would be done for a clinical anesthetic.  The physician anesthesiologist 
will monitor the patient while they are receiving and recovering from the lidocaine 
infusion. 
The experimental protocol consists of 3 basic elements: 4-minute battery of cognitive 
tasks (asynchronous with scanning), a functional MRI scan during a 4-minute block-
design pain task consisting of five 10-second stimulations with 20 second rest periods, 
and an 8-minute resting-state (task-free) functional MRI scan.  This will be performed 
first under just the IV fluid carrier infusion. Then, lidocaine will be administered, using a 
bolus+infusion strategy to reach steady-state effect-site target concentration of 1 
mcg/ml.  This level will be maintained for at approximately 20 minutes, while the above 
tasks/scans are obtained again under the low-dose lidocaine condition. When 
completed, an additional bolus and higher infusion rate of lidocaine will be administered 
to achieve an effect-site concentration of 1.5 mcg/ml.  This level will be maintained for 
approximately 16 minutes, and the above three tasks/scans repeated under the high-
dose lidocaine condition. Dosing schedules to achieve effect-site targets will be 
calculated on a per-subject basis using available modeling software  and published 
pharmacokinetic models that account for sex, age, weight, and height.  For reference, 
the total dose of lidocaine that would be administered to a prototypical 70 kg male 
subject would be <150 mg of lidocaine over the anticipated 40 minutes of infusion time. 
Structural (anatomical) scans will be obtained during transition periods of drug dosing, 
to minimize time exposed to the drug and time spent in the scanner.  These needed 
scans for subsequent analysis are typically 4 minutes or less, and time needed for drug 
levels to reach steady state are similarly 6-7 minutes.  Thus the total time spent in the 
scanner is anticipated to be less than 1 hour. 
Subjects will then be removed from the scanner.  Once sitting up, and after the 
resolution of any acute dizziness from moving through the magnetic field and/or the 
drug, they will be escorted to the adjacent recovery room. They will then be monitored 
by the anesthesiologist until fully recovered from the effects of sedation. Subjects will 
paid $150 during this recovery period.  Once it is safe to do so, their IV will be removed 


and they will be discharged from anesthesia care, anticipated to be <30 minutes after 
the end of scanning. Subjects will be reminded not to drive a vehicle or operate 
machinery after receiving lidocaine. There are no follow-up procedures.  Subjects will be 
given the PI’s contact information in the unlikely event that there are any late 
complications or questions after the study. 


============ 
References: 
1. 
Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to 
Reduce the Risk of Pulmonary Aspiration: Application to Healthy Patients Undergoing Elective 
Procedures. Anesthesiology. 2017;126(3):376-93. doi: 10.1097/aln.0000000000001452.