Acute Pain Genomic Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University of Pittsburgh
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Jacques E. Chelly, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01557751
First received: March 15, 2012
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Osteoarthritis
Postoperative Pain
Genetic: Whole blood for genotyping

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Preliminary Studies for Whole Genome Association Study (WGAS) in Acute Perioperative Pain

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • NRS-Pain with movement on POD 2 [ Time Frame: Postoperative day (POD) 2 ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 400
Study Start Date: February 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Genetic: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557751

Contacts
Contact: Katie L Vulakovich, CCRP 412.623.6382 vulakovichkl@upmc.edu

Locations
United States, Pennsylvania
UPMC Presbyterian Shadyside Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Katie L Vulakovich    412-623-6382    vulakovichkl@upmc.edu   
Principal Investigator: Jacques E Chelly, MD, PhD, MBA         
Sub-Investigator: Inna Belfer, MD, PhD         
Sub-Investigator: Feng Dai, PhD         
Sub-Investigator: Carol Greco, PhD         
Sub-Investigator: Lawrence Crossett, MD         
Sub-Investigator: Anna Lokshin, PhD         
Sponsors and Collaborators
University of Pittsburgh
  More Information

Publications:

Responsible Party: Jacques E. Chelly, Professor of Anesthesiology (with Tenure) and Orthopedic Surgery, Vice Chair of Clinical Research, Director of the Regional and Orthopedic Fellowships, Director of the Division of Acute Interventional Perioperative Pain and Regional Anesthesia, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01557751     History of Changes
Other Study ID Numbers: PRO09050171, N08PC10039, 1406-0408-CT-20481
Study First Received: March 15, 2012
Last Updated: July 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Total knee arthroplasty
Total knee replacement
Genetics of pain

Additional relevant MeSH terms:
Osteoarthritis
Pain, Postoperative
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on August 01, 2014