Acute Pain Genomic Study
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Arthritis, Osteoarthritis (OA), Post-Surgical Pain |
| Therapuetic Areas: | Musculoskeletal, Rheumatology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/13/2018 |
| Start Date: | February 2010 |
| End Date: | July 2020 |
Preliminary Studies for Whole Genome Association Study (WGAS) in Acute Perioperative Pain
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.
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.
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.
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.
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
We found this trial at
1
site
Pittsburgh, Pennsylvania 15232
Principal Investigator: Jacques E Chelly, MD, PhD, MBA
Phone: 412-623-6382
Click here to add this to my saved trials
