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Phenomics and Genomics of Clinically Relevant Chronic Postsurgical Pain (CT-Pain)

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ClinicalTrials.gov Identifier: NCT04798573
Recruitment Status : Recruiting
First Posted : March 15, 2021
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
The investigators will approach elective cardiac and thoracic surgery patients in the preoperative consultation clinic. Consenting individuals will be administered, before surgery validated pain, psychological and sleep questionnaires. These questionnaires will be repeated at 3, 6 and 12 months postoperatively (PO) to follow up the progression of early PO pain and the transition to chronicity. Participants will define clinically relevant pain by calculating a chronic pain index (CPI). In addition, the investigators will follow the development of acute postsurgical and chronic pain from before surgery up to a year after, extract DNA from blood and contrast the genetic variations of participants with clinically significant chronic pain, to identify variations associated with the development of chronic post-surgical pain.

Condition or disease
Chronic Pain Surgery

Detailed Description:

Most patients who undergo surgery heal within weeks to months and return to their baseline functional status or to an improved level of functioning. However, some patients have pain after surgery which continues. The purpose of this study is to see if there is a relationship between patient's genetic makeup (diseases that are passed on in families) and pain experience following cardiac and thoracic surgeries. This study will look for links between psychological factors, environmental factors and genetic factors in an attempt to uncover the risk for developing chronic post-surgical pain.

This study hopes to determine differences between traditional pain surveys and a basic science approach called "Phenomics" to measure chronic pain response after cardiac and thoracic surgery. Phenomics or Phenomes is the study of physical characteristics, outside influences and biochemical changes (traits or chemical characteristics) and their response to either the environment or genetic changes. Validated pain questionnaires will be administered before surgery, and will repeated at 3, 6, and 12 months postoperatively to follow up the progression of early postoperative pain and the transition to chronicity. In general, the psychological and pain questionnaires are designed to measure the following: anxiety, thoughts, feelings and reactions toward pain and stressful experiences.

In addition, the study will follow the development of acute postoperative and chronic pain from before surgery up to a year after. The investigators will extract DNA from blood and contrast the genetic variations of participants with clinically significant chronic pain, to identify variations associated with the development of chronic post-surgical pain. The blood sample will be drawn at the time of the surgery.

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Study Type : Observational
Estimated Enrollment : 10000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Phenomics and Genomics of Clinically Relevant Chronic Postsurgical Pain: A Multicenter Prospective Study
Actual Study Start Date : August 3, 2012
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Pain




Primary Outcome Measures :
  1. Post-Surgical Pain Intensity [ Time Frame: 1 year from the day of surgery ]
    Measured using the numeric rating scale (0=no pain; 10=worst pain imaginable)

  2. Pain: Measured using the McGill Pain Questionnaire- Short Form-2 (SF-MPQ-2) [ Time Frame: 1 year from the day of surgery ]
    The SF-MPQ-2 is a 22-item, expanded and revised version of the SF-MPQ designed to measure the qualities of neuropathic and non-neuropathic pain. Exploratory and confirmatory factor analyses revealed the presence of the following four factors or subscales: (1) continuous pain, (2) intermittent pain, (3) neuropathic pain, and (4) affective pain descriptor.

  3. Pain: Measured using the Self-completed Leeds Assessment of Neuropathic Symptoms and Signs (SLANSS) [ Time Frame: 1 year from the day of surgery ]
    The S-LANSS is a validated 7-item questionnaire designed to distinguish whether pain is predominately neuropathic or nociceptive in origin.

  4. Anxiety: Measured using the Anxiety Sensitivity Index-3 (ASI-3) [ Time Frame: 1 year from the day of surgery ]
    The ASI-3 is a revised version of the widely used, 16-item scale ASI that measures concerns that anxiety and anxiety-related symptoms will lead to harmful negative consequences. Each item is rated on a 5-point scale ranging from very little (0) to very much (4).

  5. Pain Catastrophizing: Measured using the Pain Catastrophizing Scale (PCS) [ Time Frame: 1 year from the day of surgery ]
    The PCS consists of 13 items describing thoughts and feelings that individuals may experience when they are in pain. Each item is rated on a 5-point scale ranging from not at all (0) to all the time (4).

  6. Pain Anxiety: Measured using the Pain Anxiety Symptoms Scale-20 (PASS-20) [ Time Frame: 1 year from the day of surgery ]
    The PASS-20 is a shortened 20-item version of the original Pain Anxiety Symptoms Scale designed to measure fear and anxiety responses specific to pain, including avoidance. The PASS-20 has four 5-item subscales, including (1) cognitive anxiety, (2) escape and avoidance, (3) fearful thinking, and (4) physiological anxiety.

  7. Pain Disability: Measured using the Pain Disability Index (PDI) [ Time Frame: 1 year from the day of surgery ]
    The PDI assesses the extent to which persistent pain interferes with an individual's ability to engage in seven different areas of everyday activity including: (1) family/home responsibilities, (2) recreation, (3) social activity, (4) occupation, (5) sexual behavior, (6) self-care, and (7) life-support activity.

  8. Posttraumatic Stress Disorder: Measured using the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C) [ Time Frame: 1 year from the day of surgery ]
    The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) is a 17-item self-report measure based on the current DSM-IV symptoms for PTSD. Respondents are asked to indicate how much they have been bothered by each symptom 5-point scale ranging from not at all (1) to extremely (5).

  9. Anxiety and Depression: Measured using The Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 1 year from the day of surgery ]
    The HADS is the most widely used scale for measuring symptoms of anxiety and depression among medical inpatients, outpatients and the general population and consists of 7 anxiety and 7 depression-related items.

  10. Somatization: Measured using the SCL-90-R-Somatization [ Time Frame: 1 year from the day of surgery ]
    The SCL-90-R is a widely-used self-report symptom inventory measuring psychological symptoms of psychiatric and medical patients. Participants rate each item on a five-point scale of distress, ranging from 0 (no distress) to 4 (extreme distress).

  11. Chronic Pain Acceptance: Measured using the Chronic Pain Acceptance Questionnaire (CPAQ) [ Time Frame: 1 year from the day of surgery ]
    The CPAQ is a 20-item questionnaire that measures how participants react and adapt to living with chronic pain. Participants respond to "how true" each item is by selecting a number from 0 ("never true") to 6 ("always true").

  12. Mindful Attention Awareness: Measured using the Mindful Attention Awareness Scale (MAAS) [ Time Frame: 1 year from the day of surgery ]
    The MAAS is a 15-item scale designed to measure a central feature of dispositional mindfulness characterized by "open or receptive awareness of and attention to" the present. Participants respond to how frequently/infrequently they experience each item by selecting one of six response options on a Likert rating scale ranging from 1 ("Almost always") to 6 ("Almost never").

  13. Pain Self Efficacy: Measured using the Pain Self-Efficacy Questionnaire (PSEQ) [ Time Frame: 1 year from the day of surgery ]
    The PSEQ is a 10-item Likert-type questionnaire, designed specifically for chronic pain, where patients are asked to rate their confidence to complete certain activities despite pain.

  14. Sensitivity to Pain Traumatization: Measured using the Sensitivity to Pain Traumatization Scale (SPTS) [ Time Frame: 1 year from the day of surgery ]
    The SPTS is a 12-item questionnaire that was designed to measure the anxiety-related cognitive, emotional and behavioural reactions to pain that resemble symptoms of a traumatic stress reaction. Each item is rated on a 5-item Likert scale (from 1 (not at all true) to 5 (entirely true)).

  15. Sleep Problems: Measured using the Sleep Problems Questionnaire [ Time Frame: 1 year from the day of surgery ]
    This is a general questionnaire that asks its questions providing responses in units of days.

  16. Sleep Quality: Measured using the Pittsburg Sleep Quality Index (PQSI) [ Time Frame: 1 year from the day of surgery ]
    The PSQI questionnaire is much more specific, identifying specific responses and reasons why patients may be having trouble sleeping such as: (1) cannot get to sleep within 30 minutes and (2) wake up in the middle of the night or early morning.


Secondary Outcome Measures :
  1. Physical Activity for Thoracic Patients: Measured using Actiwatch--64 [ Time Frame: Up to 11 days from surgery ]
    The Actiwatch-64 is a small wrist watch-like device that contains an accelerometer that records limb movements and has a memory storage capacity for up to 11 days109. The Actiwatch-64 provides a non-invasive method of collecting activity data around the clock. Activity data are downloaded to a laptop and standard sleep parameters such as latency to sleep (SOL), wake time after sleep onset (WASO), and total sleep time (TST) are inferred by software based on the presence and absence of limb movements during specified time intervals. Total activity during periods scored as not sleep is also available.

  2. Sleep Quality for Thoracic Patients: Measured using the Sleep Quality Assessment [ Time Frame: Up to 11 days from surgery ]
    Each morning after surgery, up to and including the morning of discharge home from the hospital, a Sleep Diary will be completed.

  3. Mechanical Pain Pressure: Measured using the Mechanical Pressure Pain Threshold (PPT) [ Time Frame: 1 year from the day of surgery ]
    Pain thresholds in response to mechanical pressure applied to the skin will be obtained using a Pressure Algometer.

  4. Thermal Pain and Sensory: Measured using the Thermal Pain and Sensory Thresholds [ Time Frame: 1 year from the day of surgery ]
    Thermal stimuli will be delivered using the Medoc Thermal NeuroSensory Analyzer

  5. Pain Illusion: Measured using the Thermal Grill Illusion Test [ Time Frame: 1 year from the day of surgery ]
    Participants will be required to place their right hand on four plates, two of which will be pre-cooled to 10˚C and 20˚C and two preheated to 40˚C and 50˚C. Participants will alternate between these stimuli and a grill of mixed 20˚C and 40˚C interlaced bars with 5sec intervals between applications.

  6. Pain: Measured using the Vasoconstrictor Inspiratory Gasp [ Time Frame: 1 year from the day of surgery ]
    This simple test robustly activates the sympathetic system, which aggravates neuropathic pain in some chronic pain patients. Participants will be asked to rest supine on a couch and relax with eyes closed, and to take the deepest possible inspiration and then breathe normally. Three ratings of ongoing spontaneous pain will be taken at 1, 2, and 5 min after expiration. Two baseline blood pressure (systolic, diastolic and mean arterial pressure) and pulse rate measurements will be taken just before the Gasp Test and at 1 and 2 min thereafter, just after the pain ratings. Cardiovascular parameters will be carried out using an automated blood pressure cuff.

  7. Cold Pressor Pain: Measured using the Cold Pressor Pain Test [ Time Frame: 1 year from the day of surgery ]
    The participant will immerse their right hand (above the elbow) in ice cold water and keep it there until they cannot tolerate the pain. The pain tolerance threshold will be recorded with a stopwatch, as the time to withdrawal; cut-off at 3 min. They will then use the NRS (0-100) to rate the magnitude of pain and unpleasantness.


Other Outcome Measures:
  1. Genotyping Outcomes- DNA and Biomarkers [ Time Frame: From pre-surgery to 3 month post-surgically ]
    A genome-wide exomic sequencing and full genome sequencing will be carried out in search of a common and rare variants that predispose carriers to acute post-surgical pain and the transition to pain chronicity post-surgery.


Biospecimen Retention:   Samples With DNA
We will extract DNA from blood and contrast the genetic variations of participants with clinically significant chronic pain, to identify variations associated with the development of chronic post-surgical pain.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Elective cardiac and thoracic surgery patients who agree to participate in the study
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Non- Emergency Cardiac Surgery with Midline Sternotomy OR Thoracic Surgery via VATS or Lateral Thoracotomy
  3. Written informed consent to participate in the study

Exclusion Criteria:

  1. Patient unable to understand the study protocol
  2. History of a psychotic psychiatric disorder
  3. Unable to speak English

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04798573


Contacts
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Contact: Hance Clarke, MD PhD FRCPC 416-340-4800 ext 6649 Hance.Clarke@uhn.ca
Contact: Jo Carroll 416-340-4800 ext 3243 Jo.Carroll@uhn.ca

Locations
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Canada, Ontario
Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Hance Clarke, MD    416-340-4800 ext 6649    hance.clarke@uhn.ca   
Principal Investigator: Hance Clarke, MD         
Sponsors and Collaborators
University Health Network, Toronto
Publications:
Wall PD, Jones M. Defeating pain: The war against a silent epidemic. New York, NY: Plenum Press; 1991.
Seltzer Z, Mogil JS. Pain and genetics. In: Sessle BJ, Lavigne GJ, Lund JP, Dubner R (eds). Orofacial Pain and Related Conditions. 2nd edition ed. Hanover Park, Illinois: Quintessence Publishing, 2008:69-75.
Choinière M, Watt-Watson J, Costello J, Guerriere D, Carrier M, Cogan M, Bussieres J, Guertin MC, Lespérance F, Basket R, McFetridge-Durdle J, Sullivan J. Prevalence, characterictics, and risk factors of persistent post-operative pain after cardiac surgery. Pain Research and Management. 2009;14(2):144.
Katz J. Pain begets pain - Predictors of long-term phantom limb pain and post-thoracotomy pain. Pain Forum. 1997;6:140-4.
Lu Y, Belfer I, Vatine JJ, Shir Y, Jablonski-Peetz T, Pfeffer RM, Hipp H, Sun L, Craiu R, Goldman D, Max MB, Seltzer Z. Neuropathic pain levels following surgical nerve injury are controlled by genotypes and haplotypes of COMT - the gene encoding catecholamine-o-methyltransferase.Second International Conference on Neuropathic Pain. Berlin, Germany, 2007.
Lu Y, Belfer I, Gershon E, Vatine JJ, Shir Y, Jablonski-Peetz T, Pfeffer RM, Hipp H, Livneh J, Goldman D, Max M, Seltzer Z. Do GCH1 polymorphisms control the risk for developing chronic pain in leg amputees and women postmastectomy? . Canadian Association of Genetic Epidemiology. Toronto, Canada, 2007.
Seltzer Z. Studying candidate genes for chronic pain: the example of COMT, the gene encoding Catechol-O-methyltransferase. 5th Congress of the European Federation of IASP Chapters (EFIC). Istanbul, Turkey 2006:13-6.
Sackstein M, Ramer A, Seltzer Z. Specific patterns of injury discharge are associated with receptor types in freshly injured sensory myelinated (A-) and unmyelinated (C-) fibers in rat. 8th World Congress on Pain. Vancouver, Canada, 1996.
Sabsovich I, Neumann R, Dorfman J, Storm-Mathisen OP, Otterson P, Raber R, Zeltser R, Cevor M, Seltzer Z. Spinal dorsal horn inhibitory amino acid neurons: genetic differences and response to peripheral neurectomy. 3rd Congress of the European Federation of IASP Chapters (EFIC). Nice, France, 2000.
Katz J, Clarke H. Preventive analgesia and beyond: Current status, evidence, and future directions. In: Macintyre PE, Rowbotham DJ, Howard R (eds). Clinical pain management: Acute pain 2nd ed. London: Hodder Arnold Ltd, 2008:154-98.
Derogatis L. SCL-90-R Administration, Scoring and Procedures Manual-II. Clinical Psychometric Research Towson, MD, 1983:14-5.
Sullivan M, Bishop S, Pivik J. The Pain Catastrophizing Scale: Development and Validation. . Psychological Assessment 1995;7:524-32.
Weathers F, Litz B, Huska J, Keane T. PCL-C for DSM-IV Boston: National Center for PTSD - Behavioral Science Division 1994.
Roosen K, Page MG, Kleiman V, Katz J. Sensitivity to pain traumatization scale (SPTS): Examining differences accross gender, pain history, and pain sensitivity. World Congress on Pain. Montreal, QC., 2010.
Kline R. Principles and practice of structural equation modeling. 2nd ed. New York, NY: Guilford Press; 2005.
Byrne B. Structural equation modeling with amos: Basic concepts, applications, and programming. Mahwah, NJ: Lawrence Erlbaum Associates; 2001.
Maixner W, Diatchenko L, Fillingim RB, Greenspan J, Orbach R, Slade GD, Smith S. Assessment of biopsychosocial and genetic risk factors for chronic orofacial pain: the OPPERA Study. American Pain Society Meeting. Baltimore, Maryland, 2010.

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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04798573    
Other Study ID Numbers: 12-0078
First Posted: March 15, 2021    Key Record Dates
Last Update Posted: March 15, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Chronic Pain
Pain, Postoperative
Pain
Neurologic Manifestations
Postoperative Complications
Pathologic Processes