Clinical trial NCT05460871
Conditions: Osteo Arthritis Knee Central Nervous System Sensitization
Keywords: Arthroplasty Pain Central Nervous System Sensitization Osteo Arthritis Knee Pregabalin
Sponsor: University of Iowa
Start date: 2023-02-21; Completion date: 2024-01-25
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The study purpose is to determine if giving pregabalin before and after total knee arthroplasty (TKA) can improve pain and meaningful function after surgery in patients that have central sensitization (CS).

Participants will be identified who are indicated for TKA. Interested patients will complete a standard Knee Injury and Osteoarthritis Outcomes Score (KOOS), asked their pain score (on a scale of 0 to 10), and complete the Central Sensitization Inventory (CSI). If they meet inclusion criteria and agree to participate, they will complete the informed consent before being randomized 1:1 to usual care (control group) or pregabalin (study group). The study group participants will take pregabalin starting 7 days prior to surgery. They will also be scheduled to have a pre-operative physical therapy (PT) appointment which will include tests and measures standard to PT. Tests will include a Timed Up and Go Test (TUG), a Sit to Stand 5 Times Repeat Test (5TSTS) and Patient Specific Functional Scale (SFS) measures.

On the day of surgery participants will be asked about any adverse effects of study medication and determine need to withdraw from study. The post-operative plan will be reviewed, including dose of study medication. For the pregabalin group the doses will be doubled for 7 days, then reduced for 7 days, then off. All participants will be given standard peri-operative pain management for TKA . All participants will complete standard of practice physical therapy.

After surgery (usually within 7 days) a physical therapist will perform standard post-operative evaluation and treatment for all participants. This includes a re-evaluation of the same pre-operative functional tests of TUG, 5TSTS and PSFS outcome measures. The study pharmacist will also call the patient to determine if there are any medication-related adverse effects and how much opioid medication the patient is taking at that time (morphine milligram equivalents- MME/day on average).

At the 6 week post-operative visit all participants will again complete the KOOS survey, report a pain score, complete the CSI survey and determine MME based on patient report of quantity of opioid medication used. A physical therapist will complete the functional assessment of the TUG, 5TSTS and PSFS outcome measures.

Detailed description:
The study purpose is to determine if giving pregabalin before and after total knee arthroplasty (TKA) can improve pain and meaningful function after surgery in patients that have central sensitization (CS). Central sensitization occurs when the brain (central nervous system) becomes hypersensitized and hypervigilant, over-reacting to any painful (and sometimes nonpainful) stimuli. Patients with greater central sensitization have been shown to have significantly more pain after surgery, including TKA. We are proposing to explore whether treatment with a nerve pain medication, pregabalin, can improve post-operative pain and function in these patients. This medication has been shown to improve central sensitization pain in the chronic pain setting but has not been studied for this purpose in the acute surgical pain setting.

Participants will be identified at the visit in which they are indicated for TKA. Patients indicated for a TKA will be approached about participating in the study. Either at that visit or later by phone or e-mail, interested patients will complete a standard Knee Injury and Osteoarthritis Outcomes Score (KOOS), which is part of the standard orthopedic evaluation. They will also be asked their pain score (on a scale of 0 to 10), and complete the Central Sensitization Inventory (CSI). If they meet study inclusion criteria, and they agree to participate, they will complete the informed consent (in person or on-line) and then be randomized 1:1 to usual care (control group) or pregabalin (study group). The study group participants will take pregabalin starting 7 days prior to surgery. The participant will receive usual medication counseling for this medication. They will also be scheduled to have a pre-operative physical therapy (PT) appointment at the time of their pre-op visit, which will include tests and measures standard to PT, but must include a Timed Up and Go Test (TUG), a Sit to Stand 5 Times Repeat Test (5TSTS) and Patient Specific Functional Scale (SFS) measures.

On the day of surgery participants will be asked about any adverse effects of study medication, and determine need to withdraw from study (for any reason). The post-operative plan will also be reviewed, including dose of study medication, for the pregabalin group. For the pregabalin group the doses will be doubled for 7 days, then reduced for 7 days, then off. All participants will be given standard peri-operative pain management for TKA (a nerve block and/or spinal unless contraindicated, anti-inflammatory drugs (NSAID) and acetaminophen (unless contraindicated) as well as oral opioid (usually oxycodone or hydromorphone) to use as needed for severe pain. All participants will complete standard of practice physical therapy on day of surgery or until discharged to home.

After surgery (usually within 7 days) a physical therapist will perform standard post-operative evaluation and treatment for all participants. This includes a re-evaluation of the same pre-operative functional tests of TUG, 5TSTS and PSFS outcome measures. At this time, the pharmacist will also call the patient to determine if there are any medication-related adverse effects and how much opioid medication the patient is taking at that time (morphine milligram equivalents- MME/day on average).

Standard follow-up after TKA is 6 weeks. At this visit all participants will again complete the KOOS survey, report a pain score, complete the CSI survey and determine, based on patient report, of quantity of opioid medication used (MME). A physical therapist will complete the functional assessment of the TUG, 5TSTS and PSFS outcome measures.

Arms: arm 1: Participants will receive standard peri-operative pain management arm 2: Participants will receive pregabalin orally 75mg twice daily x 7 days prior to surgery, 150mg twice daily x 7 days after surgery, followed by 75mg twice daily x 7 days. Then Stop.
Interventions: intervention 1: Pregabalin 75mg
Intervention descriptions: intervention 1: participants will receive pregabalin orally 75mg twice daily x 7 days prior to surgery, then 150mg twice daily x 7 days after surgery, followed by 75mg twice daily x 7 days, then stop.

Protocol documents:
Prot_SAP_000.pdf: 
 
Evaluating the Efficacy and Safety of Pregabalin in Total Knee Arthroplasty 
Patients with Central Sensitization 
 
NCT# 05460871  
 
 
 
 
 
 
 
Lee Kral, PharmD 
Document Date:  September 14, 2023 
 
 


Protocol: 
Following the consent process the participants will be asked to participate in the following: 
1. Participants will complete Central Sensitization Inventory (CSI) and the Columbia Suicide 
Severity Rating (CSSR) as well as any necessary labs. These will be done in person at the 
time of consent/enrollment. If the participant answers Yes on any of the CSSR questions, 
they will exit the study. If any participant scores < 40 on the CSI, they will exit the study. 
 
2. If they still qualify for the study, they will complete (1) the Baseline Subject Demographic 
form, (2) the Pain, Enjoyment of Life and General Activity form (PEG-3), and (3) the Knee 
Injury and Osteoarthritis Outcomes Score (KOOS). These will be done in person at the pre-
op visit. 
 
3. All participants will meet with a physical therapist prior to surgery to assess baseline 
functional levels using established assessment surveys. The approximate time to complete 
these assessments is 30 minutes. 
The surveys used include: Timed Up and Go (TUG) 
Stand-Up, Sit-Down (STS) 
Patient-Specific Functional Scale Assessment (PSFS) 
 
3. Participants are randomized at the pre-op visit to standard of care vs study treatment 
arm using a computer-generated block randomization sequence. The allocation of 
concealment will be ensured using a sealed envelope technique. 
 
4. If the participant is not randomized to the study medication arm, they will proceed with 
usual peri-operative management. 
 
5. If the participant is randomized to study medication arm, they will be directed to the 
UIHC Discharge Pharmacy to retrieve the study drug. Additionally, they will be provided 
information about the medication, possible side effects and dosing schedule. 
Dosing Schedule 
Pre-surgery (days 1-7) pregabalin 75mg twice daily 
Post-surgery (days 1-7) pregabalin 150mg twice daily, then (days 8-14) pregabalin 75mg 
twice daily 
 
6. Day of Surgery (DOS): Someone from the research team will meet with all participants in 
DOSA to (1) answer any questions about continued participation in the study. For those 
participants in the study medication arm, the research team member will also evaluate if 
they have (2) completed the study medication schedule, (3) determine if they have noticed 
any side effects from the medication (including the CSSR scale), and (4) remind the 
participant of post-surgical medication dosing schedule. If the participant did not tolerate 
the study medication they will exit the study and continue to receive standard surgical care. 
If the patient answers Yes to any of the CSSR items, they will be advised to seek out 
behavioral healthcare. If they answer Yes to questions 4,5, or 6, they will be immediately 
taken to the ED by study team member for evaluation. They will stop the study medication 
and exit the study at that time. Proceeding with surgery will be deferred to the primary 
surgery team. This visit is expected to take less than 15 minutes. 
 
7. All participants undergo a post-operative Physical Therapy assessment, which normally 


occurs within a week of surgery per standard of care. At that time, the functional levels as 
outlined above including TUG, STS, and PSFS will be re-evaluated. The approximate time 
spent is 30 minutes. 
 
8. All participants will be contacted by the study pharmacist about 7 days after surgery by 
telephone. The pharmacist will also determine the amount of other pain medications that 
have been needed for pain relief for all participants. The goal of this assessment is to 
determine how the participant is faring with the study medication (if randomized to the 
study medication arm) and other pain medications. The pharmacist will review the study 
medication dosing schedule with these participants and re-assess with the CSSR scale. If 
the participant did not tolerate the study medication they will exit the study and continue to 
receive standard post-surgical care. If the patient answers Yes to any of the CSSR items, 
they will be advised to seek out behavioral healthcare. If they answer Yes to questions 4,5, 
or 6, they will be advised to seek immediate medical attention or local EMS will be contacted 
by the pharmacist. They will stop the study medication and exit the study at that time. 
 
9. Patients will have a 6-week post-operative visit with their surgical team and research 
study team. At this time, all participants will again complete the Knee Injury and 
Osteoarthritis Outcomes Score (KOOS), the PEG-3 pain survey, and the Central Sensitization 
Inventory (CSI) assessments. Also the participant will be asked to report how much opioid 
medication (if any) they are taking and the physical therapist will repeat the functional tests 
(TUG, STS, PSFS). The time to complete these evaluations is approximately 60 minutes. 
 
10. This will complete the study participation. 
 
Analysis/Statistical Plan: 
Treatment-stratified summary statistics will be calculated for all baseline measures, 
including demographics and clinical outcomes. Categorical measures will be presented as 
counts and percentages. Continuous measures will be assessed for normality and presented 
as either means and standard deviations or medians and interquartile ranges. Assessments 
of between-group differences will be conducted for all baseline non-subscale measures using 
Fisher’s exact, two-sample t-, or Wilcoxon rank sum tests. Between-group differences for 
baseline subscale measures (following a 5-point Likert scale) will be assessed using 
cumulative logistic regression to utilize the ordinality of the measure. 
Between-group changes (baseline to week 6) in the primary outcome (KOOS- ADL) and 
secondary outcomes (KOOS subscale scores (pain, symptoms, sports/recreation, and quality 
of life subscales, pain scores, differences Timed Up and Go Test (TUG), the Sit-to-Stand Test 
(STS) and the Patient Specific Functional Scale (PSFS) will be assessed by calculating the 
within-subject differences. Distributions for each outcome’s 6-week change will be 
examined. Measures with normally distributed differences will follow the two-sample t-test 
to compare changes between treatment groups, and measures with non-normally 
distributed differences will follow the Wilcoxon rank sum test. Tests with p-values < 0.05 will 
be considered statistically significant. 
As an exploratory outcome, we will investigate the relationship between 6-week changes in 
CSI scores and changes in pain and function outcomes. Associations between normally and 
non-normally distributed measures will be investigated using Pearson’s and Spearman’s 
correlations, respectively. 


Adverse effects will be calculated for each treatment group and presented counts and 
percentages. 
 

ICF_001.pdf: 
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Evaluating the Efficacy and Safety of Pregabalin in Total Knee Arthroplasty Patients with 
Central Sensitization 
 
NCT# 05460871  
 
 
 
 
 
 
 
Lee Kral, PharmD 
Document Date:  August 15, 2023 
 
 


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INFORMED CONSENT DOCUMENT 
 
Project Title: Evaluating the Efficacy and Safety of Pregabalin in Total Knee 
Arthroplasty Patients with Central Sensitization 
 
Principal Investigator:  Lee Kral 
 
Research Team Contact: 
Lee Kral 319-356-1616 (pager #2337) 
 
This consent form describes the research study to help you decide if you want to 
participate.  This form provides important information about what you will be asked to do 
during the study, about the risks and benefits of the study, and about your rights as a 
research subject.   
 
• If you have any questions about or do not understand something in this form, you 
should ask the research team for more information.   
• You should discuss your participation with anyone you choose such as family or 
friends.   
• Do not agree to participate in this study unless the research team has answered 
your questions and you decide that you want to be part of this study.  
 
WHAT IS THE PURPOSE OF THIS STUDY? 
 
This is a research study.  We are inviting you to participate in this research study because 
you have grade 3 to 4 osteoarthritis and you are going to undergo a total knee 
replacement (arthroplasty).   
 
The purpose of this research study is to compare pain and function after surgery between 
patients who receive a medication (pregabalin) to reduce central sensitization and those 
who do not receive the medication.  We would like to see if the medication can offer 
better pain relief and better outcomes for patients who have central sensitization.  We will 
also evaluate whether the medication might reduce the central sensitization itself.  The 
medication we are going to use (pregabalin) is a nerve pain medication that has been used 
in patients undergoing knee arthroplasty in the past and is also used commonly for 
chronic pain associated with central sensitization.  
 
HOW MANY PEOPLE WILL PARTICIPATE? 
 
Approximately 400 people will be recruited for this study conducted by investigators at 
the University of Iowa.   
 
 
HOW LONG WILL I BE IN THIS STUDY? 
 
If you agree to take part in this study, you would be involved in the study for up to 6 
weeks following surgery.  It will include two visits with the surgery team and study staff 


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for pre-surgery work-up and a 6-week post-surgery follow-up (usually about 30 minutes 
per visit).  You will also work with a physical therapist doing standard physical therapy 
appointments.  These visits may vary from 1-3 times/week, depending on your needs.  It 
minimally will include a pre-surgery visit, an evaluation within about a week after 
surgery with a physical therapist, and a visit at 6 weeks after surgery.  These are usually 
about 30 minutes per visit.   
 
The study team will also visit with you on the day of surgery.  As part of this research 
study, if you receive study medication the study team will ask how you are faring with 
the study medication (e.g. If you are taking the study medication and if you are 
comfortable proceeding in the study).  This will take about 15 minutes.  The study team 
will also call you about 1 week after surgery to check in with you and ask some questions 
about how you are doing with your medications (usually about 10-15 minutes).  
 
WHAT WILL HAPPEN DURING THIS STUDY? 
 
If you meet the criteria to participate in the study and sign the consent form, you will 
complete surveys about your nervous system sensitivity to pain (Central Sensitization 
Inventory) and your risk of suicide (Columbia Suicide Severity Rating Scale). We will 
collect the lab value for kidney function from your medical record.  If you have not had 
this lab drawn in the previous 3 months, we will draw your blood and check that lab 
value for purposes of the study.  If you are a woman capable of becoming pregnant, we 
will also do a pregnancy test. 
 
• If you still meet the criteria to participate in the study, you will complete a 
questionnaire about general demographic information, and surveys about your 
knee pain (Pain, Enjoyment of Life, and General Activity scale – PEG-3) and 
function (Knee Injury and Osteoarthritis Outcome Score – KOOS).  These will be 
done in person in the clinic. 
• You will meet with a physical therapist to evaluate your knee function.  There are 
at least three assessments that are done.  The Timed Up and Go (TUG) measures 
how long it takes to stand from a seated position and walk 3 meters (about 10 
feet).  The Stand-Up, Sit-Down (STS) measures how long it takes for you to stand 
up and sit down five times.  The Patient-Specific Functional Scale assessment 
(PSFS) asks you about activities that you are unable to perform or having 
difficulty with and would like to improve.  You may also be completing some 
basic exercises and learning how to use an assistive device for support after 
surgery. 
• You will be randomized (assigned by chance to either receive the study 
medication or continue without the medication (usual care).  You will have a 
50/50 chance of receiving the study medication.   
• If you are not randomized to the study medication group, you will proceed with 
the stand of care for total knee arthroplasty patients. 
• If you are randomized to the study medication group, you will pick up your study 
medication at the UIHC Discharge Pharmacy.  The team and the pharmacist will 
provide you with information about the medication and possible side effects.  


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Your dosing schedule can be found in the Table below. 
 
• Someone from the research team will meet with you on the day of surgery in the 
Day of Surgery Area (DOSA).  They will answer any questions about continued 
participation in the study.  For those in the study medication group, the research 
team will ask if you have completed the pre-surgery medication regimen and ask 
you about any possible side effects that you might be having with the medication.  
If you did not tolerate the medication, you will be released from the study and 
receive usual surgical care.  The study team will also ask you to answer the 
suicide severity rating scale.  If you feel that your mood is not stable or are 
thinking about suicide, they will immediately take you to get help.  If this does 
occur, you will be released from the study and the surgery team will re-evaluate 
your care.  They will remind you of the dosing of the medication after surgery.  
You will take your morning dose of study medication on the day of surgery.  
While in the hospital, nursing staff will give you the medications.  Your dosing 
schedule can be found in the Table below.      
• You will receive a phone call from the study pharmacist about 7 days after 
surgery to see how you are doing and see how much pain medication you are 
taking. She will also answer any questions that you might have.  She will also ask 
you to complete the suicide severity rating scale.  If you feel that your mood is not 
stable or are thinking about suicide, she will immediately call your local 
emergency services to get you help.  If this does occur, you will be asked to stop 
the medication and will be released from the study.  She will ask you about any 
other side effects with your study medication or other pain medication.  Lastly, if 
you will be continuing the study medication, she will remind you of your last set 
of study medication doses.  These can be found in the Table above. 
• You will meet a physical therapist within a week after surgery.  At your outpatient 
physical therapy evaluation, you will proceed with standard of care post-operative 
therapy and be re-evaluated on the 3 functional assessments (TUG, STS, and 
PSFS).  You will work with your outpatient physical therapy team per the 
standard of care for total knee arthroplasty over the next 10 – 12 weeks (after the 
end of the study) as part of standard care. 
• At your 6-week post-operative follow-up visit (either in person or via 
telemedicine) with the surgery and research teams, you will complete the surveys 
(KOOS, PEG-3 and CSI) again.  If your follow-up is on telemedicine, we will 
send you secure REDCap links to your email.  If you forget or are unable to 
complete these, we will contact you by telephone.  You will also be asked about 
 
Pre-
Surgery 
 
Post-
Surgery 
Post-
Surgery 
Time 
Days 1-7 
 
Days 1-7 
Days 8-14 
7:00 
AM 
1capsule 
(75 mg) 
 
2 capsules 
(150 mg) 
1 capsule 
(75 mg) 
7:00 
PM 
1 capsule 
(75 mg) 
 
2 capsules 
(150 mg) 
1 capsule 
(75 mg) 


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how much opioid medication you are taking (if any).  You will report any unused 
study medication and dispose of any remaining medication. 
• At the 6-week point of time from the date of surgery, you will complete the 
functional assessments again with your physical therapist. 
• The information reported on the KOOS, PEG-3, and CSI surveys as well as the 
physical therapy assessments and the amount of pain medication you need will be 
taken from your medical record and analyzed in this study.  We will collect any 
lab values (e.g. kidney function, pregnancy test) that were checked.  We will also 
review any information that you may have shared with the study team in phone 
calls or concerns that you may have had with regard to side effects. 
• This will complete your study participation. 
 
WHAT ARE THE RISKS OF THIS STUDY? 
 
You may experience one or more of the risks indicated below from being in this study. In 
addition to these, there may be other unknown risks, or risks that we did not anticipate, 
associated with being in this study. All of the side effects, if they occur, are expected to 
resolve within 72 hours of stopping the medication. 
 
The possible risks or side effects from taking the study medication (pregabalin) are as 
follows.  Other medications that at taken at the same time as pregabalin (like opioid 
medications) may increase the risk of these side effects 
 
Less Likely / Less Common (10% - 35%) 
Mild (these resolve when the medication is stopped) 
• 
Fluid retention 
• 
Weight gain 
• 
Dizziness 
• 
Uncoordinated walking 
• 
Sedation 
• 
Erectile dysfunction (males) 
• 
Lack of libido 
• 
Orgasm incapacity 
 
Rare (less than 10%) 
Life Threatening (this resolves when the medication is stopped but may require medical 
treatment) 
• 
Swelling of the face/throat 
• 
Suicidal thoughts 
Serious (these resolve when the medication is stopped) 
• 
Decreased platelet production 
• 
Increased liver enzymes 
• 
Skin redness 
• 
Blisters and hives/rash 


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• 
Shortness of breath 
• 
Wheezing 
 
Mild (These resolve when the medication is stopped) 
• 
Increased appetite 
• 
Constipation 
• 
Excessive salivation (saliva production) 
• 
Nausea and/or Vomiting 
• 
Dry mouth 
• 
Fatigue or lack of energy or strength 
• 
Headache 
• 
Difficulty with memory, possible confusion, or disturbance in thinking 
• 
Disturbance in speech 
• 
Insomnia 
• 
Tremor 
• 
Blurred/Double vision 
• 
Euphoria (feeling extremely happy or “high”) 
• 
Upper airway congestion 
• 
Joint pain 
• 
Muscle spasm 
 
If your physician prescribes you opioid medication, there may be additional side effects 
to those listed above. Your care team will describe the potential effects to you. 
 
WHAT ARE THE BENEFITS OF THIS STUDY? 
 
We don’t know if you will benefit from being in this study. 
 
However, we hope that, in the future, other people might benefit from this study because 
we may know if prescribing a medication to reduce central sensitization will improve 
pain and function following knee replacement surgery.   
 
WHAT OTHER TREATMENT OPTIONS ARE THERE? 
 
Before you decide whether or not to be in this study, your doctor will discuss the other 
options that are available to you.  You could have the surgical procedure without using 
the study medication. You can choose not to participate. 
 
WILL IT COST ME ANYTHING TO BE IN THIS STUDY? 
 
You will not have any additional costs for being in this research study. If you are 
randomized to receive the study medication (pregabalin), you or your insurance will not 
be charged for it.  If we have to draw blood for the lab test or perform a pregnancy test, 
the study will also cover those costs. 
 


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You and/or your medical/hospital insurance carrier will remain responsible for your 
regular medical care expenses. 
 
WILL I BE PAID FOR PARTICIPATING? 
 
You will not be paid for being in this research study.   
 
WHO IS FUNDING THIS STUDY? 
 
The University and the research team are receiving no payments from other agencies, 
organizations, or companies to conduct this research study.   
 
A grant was awarded by the Anesthesia Research Institute to cover the cost of the study 
medication.  No one on the research team will receive a direct payment or increase in 
salary for conducting this study. 
 
WHAT IF I AM INJURED AS A RESULT OF THIS STUDY? 
• 
If you are injured or become ill from taking part in this study, medical treatment is 
available at the University of Iowa Hospitals and Clinics. 
• 
The University of Iowa does not plan to provide free medical care or payment for 
treatment of any illness or injury resulting from this study unless it is the direct result of 
proven negligence by a university employee.  
• 
If you experience a research-related illness or injury, you and/or your medical or 
hospital insurance carrier will be responsible for the cost of treatment. 
 
 
WHAT ABOUT CONFIDENTIALITY? 
 
We will keep your participation in this research study confidential to the extent permitted 
by law.  However, it is possible that other people such as those indicated below may 
become aware of your participation in this study and may inspect and copy records 
pertaining to this research.  Some of these records could contain information that 
personally identifies you.  
• 
federal government regulatory agencies,  
• 
auditing departments of the University of Iowa, and  
• 
the University of Iowa Institutional Review Board (a committee that reviews and     
approves research studies)  
  
To help protect your confidentiality, we will keep the information from the study secured 
so only authorized people working on this study can obtain.  All paper data will be kept 
in a locked cabinet.  Electronic data has password protections and stored behind UIHC 
approved data security systems.  If we write a report or article about this study or share 
the study data set with others, we will do so in such a way that you cannot be directly 
identified. 
 
The University of Iowa Hospitals and Clinics generally requires that we document your 


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participation in research occurring in a University of Iowa Health Care facility.  This 
documentation will be in either your medical record or a database maintained on behalf 
of the institution reflecting that you are participating in this study. The information 
included will provide contact information for the research team as well as information 
about the risks associated with this study. We will keep this Informed Consent Document 
in our research files; it will not be placed in your medical record chart. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law.  A copy of the informed consent document will be available on 
this website.  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. 
  
WILL MY HEALTH INFORMATION BE USED DURING THIS STUDY? 
 
The Federal Health Insurance Portability and Accountability Act (HIPAA) requires The 
University of Iowa Health Care to obtain your permission for the research team to access 
or create “protected health information” about you for purposes of this research study.  
Protected health information is information that personally identifies you and relates to 
your past, present, or future physical or mental health condition or care.  We will access 
or create health information about you, as described in this document, for purposes of this 
research study.  Once The University of Iowa Health Care has disclosed your protected 
health information to us, it may no longer be protected by the Federal HIPAA privacy 
regulations, but we will continue to protect your confidentiality as described under 
“Confidentiality.” 
 
We may share your health information related to this study with other parties including 
federal government regulatory agencies, the University of Iowa Institutional Review 
Boards and support staff.  
 
You cannot participate in this study unless you permit us to use your protected health 
information.  If you choose not to allow us to use your protected health information, we 
will discuss any non-research alternatives available to you.  Your decision will not affect 
your right to medical care that is not research related.  Your signature on this Consent 
Document authorizes The University of Iowa Health Care to give us permission to use or 
create health information about you. 
 
Although you may not be allowed to see study information until after this study is over, 
you may be given access to your health care records by contacting your health care 
provider. Your permission for us to access or create protected health information about 
you for purposes of this study has no expiration date. You may withdraw your permission 
for us to use your health information for this research study by sending a written notice to 
Dr. Lee Kral, Department of Anesthesia, The University of Iowa Hospitals and Clinics, 
Iowa City, IA  52242 However, we may still use your health information that was 
collected before withdrawing your permission.  Also, if we have sent your health 
information to a third party, such as the study sponsor, or we have removed your 


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identifying information, it may not be possible to prevent its future use.  You will receive 
a copy of this signed document. 
 
IS BEING IN THIS STUDY VOLUNTARY? 
 
Taking part in this research study is completely voluntary.  You may choose not to take 
part at all.  If you decide to be in this study, you may stop participating at any time.  If 
you decide not to be in this study, or if you stop participating at any time, you won’t be 
penalized or lose any benefits for which you otherwise qualify. 
 
What if I Decide to Drop Out of the Study? 
 
Leaving the study early may cause you to experience the following harms or discomforts: 
you may have more pain after your knee surgery.  
 
Will I Receive New Information About the Study while Participating? 
 
If we obtain any new information during this study that might affect your willingness to 
continue participating in the study, we’ll promptly provide you with that information. 
 
Can Someone Else End my Participation in this Study? 
Under certain circumstances, the researchers might decide to end your participation in 
this research study earlier than planned.  This might happen because in our judgement it 
would not be safe for you to continue, or you developed an allergy to the study 
medication. 
 
WHAT IF I HAVE QUESTIONS? 
 
We encourage you to ask questions.  If you have any questions about the research study 
itself, please contact: Dr. Lee Kral, Department of Anesthesia, 319-356-1616 (pager 
#2337) If you experience a research-related injury, please contact: Dr. Lee Kral, 
Department of Anesthesia, 319-356-1616 (pager #2337).  
 
If you have questions, concerns, or complaints about  your rights as a research subject or 
about research related injury, please contact the Human Subjects Office, 105 Hardin 
Library for the Health Sciences, 600 Newton Rd, The University of Iowa, Iowa City, IA  
52242-1098, (319) 335-6564, or e-mail irb@uiowa.edu.  General information about being 
a research subject can be found by clicking “Info for Public” on the Human Subjects 
Office web site, http://hso.research.uiowa.edu/. To offer input about your experiences as 
a research subject or to speak to someone other than the research staff, call the Human 
Subjects Office at the number above. 
 
 
 
 
 
 


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Page 10 of 10 
 
 
This Informed Consent Document is not a contract. It is a written explanation of what 
will happen during the study if you decide to participate. You are not waiving any legal 
rights by signing this Informed Consent Document. Your signature indicates that this 
research study has been explained to you, that your questions have been answered, and 
that you agree to take part in this study.  You will receive a copy of this form. 
 
 
Subject's Name (printed): 
 
 
____________________________________________ 
 
 
 
 
 
 
___________________________________       _______________________________ 
(Signature of Subject)  
 
 
 
 
(Date) 
 
 
 
 
Statement of Person Who Obtained Consent 
 
I have discussed the above points with the subject or, where appropriate, with the 
subject’s legally authorized representative.  It is my opinion that the subject understands 
the risks, benefits, and procedures involved with participation in this research study. 
 
 
______________________________________            ___________________________ 
(Signature of Person who Obtained Consent) 
 
(Date)