Osteoarthritis, Postoperative Pain
Conditions
Keywords
Total knee arthroplasty, Total knee replacement, Genetics of pain
Brief summary
In preparation for future large-scale genome wide association studies, reliable methods must be developed for measuring perceived pain and for estimating the effects of potentially confounding factors such as appropriate covariates. The major objectives of our pilot investigation are to develop optimal methods to characterize the primary endpoint of the study-knee pain, and to gather preliminary data on genetic markers in the human genome that are associated with a certain pain phenotype. The specific issues for this study will be to carry out a preliminary gene association analysis of acute perioperative pain in individuals undergoing total knee replacement and to define a pain phenotype that is composed of multidimensional domains such as opioid consumption, inflammatory markers, anxiety level, degree of catastrophizing, etc. This pain phenotype has to be sensitive enough to pick up changes in pain experience that can be attributed to single nucleotide polymorphisms.
Detailed description
In spite of advances in postoperative management and the standardization of postoperative care, there is a wide variability in the degree of pain relief achieved which cannot be accounted for. The aim of this study is to devise a method for defining a pain phenotype sensitive enough to detect differences in genetic makeup between individuals who undergo a standard surgical procedure (total knee replacement). This methodology will serve as a pilot study for future genome wide association studies. Given the multidimensional aspects of pain experience, the phenotype will be combined of various dimensions comprising postoperative pain. Reports about single nucleotide polymorphisms (SNPs), which account for some of the variability of pain, have been reported in the literature using different pain models. To test the sensitivity of our method of phenotyping, the investigators aim to determine if variability in our clinical phenotypes can be explained by some of the SNPs published in the literature. Patients scheduled for elective unilateral primary total knee arthroplasty will be asked to report on various clinical pain variables, fill psychometric questionnaires, be subjected to quantitative sensory testing, genotyped for a genes associated with pain, and additional SNPs. A composite pain profile will be composed for each patient initially examining five candidate genes and related SNPs to find out the SNPs that are significantly associated with given pain phenotypes. Samples will be banked for future study of other genes associated with pain. Other clinical variables will be collected (e.g. opioid consumption). At six and twelve months, psychological questionnaires and pain questionnaires will be sent to patient. A model using pain during physical therapy as the dependent variable will be fit to the data. Knee joint fluid, urine, and serum will be collected from approximately 30% of the subjects who provide their additional consent cytokine and other inflammatory marker analysis. All biological specimens will be banked for future analysis. This is a pilot, preliminary study which will assess patients prospectively and attempt to correlate markers on genes and single nucleotide polymorphisms with patient phenotypes. This method which will serve as the foundation for a future genome wide association study of pain. This is a preliminary, developmental, prospective follow-up study to develop a tool that will be sensitive and specific enough to be used in a large-scale candidate genome association pain study.
Interventions
GENETICWhole blood for genotyping
This study requires genotyping by extracting DNA from blood sample. A blood sample will be drawn once during visit 2 (day of surgery) or any other time prior to that after the signing of informed consent. Four vacutainers of which hold 8.5 mL will be drawn during this time totaling approximately 34 mL of blood which completes the genomic sampling portion of the study.
Sponsors
National Institutes of Health (NIH)
National Institute of Dental and Craniofacial Research (NIDCR)
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 * Undergoing a primary, unilateral total knee arthroplasty for the first time * Willing and able to provide informed consent * Caucasian * Non-hispanic
Exclusion criteria
* Contraindication or refusal for peripheral nerve blocks * Any chronic pain condition which may confound the study per investigator's opinion * Chronic opioid dependence per investigator's opinion * Any diagnosis for total knee arthroplasty other than degenerative joint disease or osteoarthritis * Evidence of clinical dementia, dementia, delirium, or any cognitive disorder which inhibits the subject's ability to comprehend and cooperate with researchers * Revision or any knee surgery that is not a primary, unilateral, elective total knee arthroplasty being performed for the first time * Any criteria that in the investigator's opinion would prohibit the subject from following * Hispanic ethnicity * Any race other than caucasian * Subjects with knee flexion contracture (which is clinically defined for the purpose of our protocol as more than 15 degrees of knee contracture) * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NRS-Pain With Movement on POD 2 | Postoperative day (POD) 2 | The primary endpoint is the pain reported by subjects, using the NRS-Pain with movement on the second day after surgery.The assumption behind this study is that certain genetic variants (e.g. single-nucleotide polymorphism (SNP) are responsible for part of total variation of certain clinical phenotypes (e.g. post-operative pain here). Numeric Rating Score Pain Assessment (0-10 scale where 0 indicates no pain at all and 10 indicates the worst pain imaginable) on Post Op Day 2, Pain with Movement |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Total Knee Arthroplasty Subjects Who Are Genotyped All patients will have whole blood drawn for genotyping, and participate in the various assessments (psychosocial questionnaires, qualitative sensory testing, etc).
Whole blood for genotyping: This study requires genotyping by extracting DNA from blood sample. A blood sample will be drawn once during visit 2 (day of surgery) or any other time prior to that after the signing of informed consent. Four vacutainers of which hold 8.5 mL will be drawn during this time totaling approximately 34 mL of blood which completes the genomic sampling portion of the study. | 156 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | Total Knee Arthroplasty Subjects Who Are Genotyped |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 64 Participants |
| Age, Categorical Between 18 and 65 years | 92 Participants |
| Age, Continuous | 64.23 years |
| Region of Enrollment United States | 156 Participants |
| Sex: Female, Male Female | 90 Participants |
| Sex: Female, Male Male | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 156 |
| other Total, other adverse events | 0 / 156 |
| serious Total, serious adverse events | 0 / 156 |
Outcome results
Primary
NRS-Pain With Movement on POD 2
The primary endpoint is the pain reported by subjects, using the NRS-Pain with movement on the second day after surgery.The assumption behind this study is that certain genetic variants (e.g. single-nucleotide polymorphism (SNP) are responsible for part of total variation of certain clinical phenotypes (e.g. post-operative pain here). Numeric Rating Score Pain Assessment (0-10 scale where 0 indicates no pain at all and 10 indicates the worst pain imaginable) on Post Op Day 2, Pain with Movement
Time frame: Postoperative day (POD) 2
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Total Knee Arthroplasty Subjects Who Are Genotyped | NRS-Pain With Movement on POD 2 | 2.83 units on a scale |