Clinical trial NCT02511483: Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain
Official title: Contribution of COMT Haplotypes in Propranolol Analgesic Efficacy for Treating Post-surgical Pain After Laparoscopic Hemicolectomy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Postoperative Pain
Keywords: COMT
Beta-blocker
Hemicolectomy
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2015-07-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized, double-blind, placebo controlled clinical trial. The main purpose of this study is to determine if postsurgical pain ratings are improved with treatment with oral Propranolol, and if the effectiveness of treatment can be modified by the presence or absence of SNPs (Single Nucleotide Polymorphism) associated with Cathecol-O-MethylTransferase (COMT) and mu-opioid receptor (MOR1) activity. The treatment period will last for three days and the observation period will last for six months. Effectiveness of treatment will be assessed by means of morphine consumption through quantitative evaluation of IV-PCA (Patient Controlled Analgesia) morphine as primary outcome measure.


Eligibility criteria: Inclusion Criteria:

* Elective laparoscopic hemicolectomy surgery.
* Self-reported Caucasians.
* ASA (American Society of Anesthesiologists) physical status of I or II.
* Agrees to provide signed and dated informed consent form.
* Willingness to agree with the Biobanking policy.

Exclusion Criteria:

* Uncontrolled medical or psychiatric conditions.
* Severe mental impairment.
* History of major depressive disorder, psychotic disorder or schizophrenia, and/or manic episodes within the past year.
* Active alcoholism within the past 6 months.
* Psychoactive recreational drug abuse within the past 6 months including MDMA, Ketamine, hallucinogens such as LSD and/or sympathomimetics such as Cocaine.
* Inability to comprehend pain assessment.
* Pregnancy and/or breast-feeding.
* Known hypersensitivity to Beta Blockers or Opioids.
* Currently taking Propranolol.
* Currently taking other hypotensive treatments.
* Currently taking Opioids.
* Patients with asthma or reactive airway disease.
* Patients with cardiac arrhythmia, coronary artery disease, congestive heart failure.
* Patients with renal failure or dialysis.
* Patients with liver insufficiency.
* Heart rate less than 60bpm or diastolic blood pressure \<50 mmHg during the preoperative visit.

Primary outcomes:
measure: Total morphine delivered by IV-PCA
timeFrame: Day II Post-op
Secondary outcomes:
measure: Pressure Pain Threshold by digital pressure algometer
timeFrame: Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
measure: Hyperalgesia test by von Frey hair
timeFrame: Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
measure: Pain measured by the Numerical pain Rating Scale
timeFrame: Pre-op visit, one evaluation during the first 8 Post-op hours, Day I Post-op, Day II Post-op, 4 weeks Post-op, 3 month Post-op, 6 months Post-op
measure: Somatization, depression and anxiety by SCL-90-R subscales
timeFrame: Pre-op visit
measure: Sleep quality by PSQI
timeFrame: Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
measure: Pain quality by sfMGPQ
timeFrame: one evaluation during the first 8 Post-op hours, Day I Post-op, Day II Post-op
measure: Post-operative Chronic Pain by PQRS
timeFrame: Pre-op visit, Day II Post-op, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
Other outcomes:
measure: COMT-haplotypes by blood sampling genotyping
timeFrame: Pre-op, Day III Post-op, 4 weeks Post-op
Locations:
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
Study officials:
affiliation: Anesthesia Department McGill University
name: Luda Diatchenko, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Orrey DC, Halawa OI, Bortsov AV, Shupp JW, Jones SW, Haith LR, Hoskins JM, Jordan MH, Bangdiwala SI, Roane BR, Platts-Mills TF, Holmes JH, Hwang J, Cairns BA, McLean SA. Results of a pilot multicenter genotype-based randomized placebo-controlled trial of propranolol to reduce pain after major thermal burn injury. Clin J Pain. 2015 Jan;31(1):21-9. doi: 10.1097/AJP.0000000000000086.
citation: Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab.
citation: Zaugg M, Tagliente T, Lucchinetti E, Jacobs E, Krol M, Bodian C, Reich DL, Silverstein JH. Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology. 1999 Dec;91(6):1674-86. doi: 10.1097/00000542-199912000-00020.
citation: Schweinhardt P, Abulhasan YB, Koeva V, Balderi T, Kim DJ, Alhujairi M, Carli F. Effects of intravenous propranolol on heat pain sensitivity in healthy men. Eur J Pain. 2013 May;17(5):704-13. doi: 10.1002/j.1532-2149.2012.00231.x. Epub 2012 Oct 16.
citation: Pranevicius M, Pranevicius O. Non-opioid anesthesia with esmolol avoids opioid-induced hyperalgesia and reduces fentanyl requirement after laparoscopy. Anesth Analg. 2009 Mar;108(3):1048. doi: 10.1213/ane.0b013e3181938f3f. No abstract available.
citation: Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth. 2004 Dec;93(6):799-805. doi: 10.1093/bja/aeh268. Epub 2004 Sep 17.
citation: Chen YW, Chu CC, Chen YC, Hung CH, Wang JJ. Propranolol elicits cutaneous analgesia against skin nociceptive stimuli in rats. Neurosci Lett. 2012 Aug 30;524(2):129-32. doi: 10.1016/j.neulet.2012.07.036. Epub 2012 Jul 26.
citation: Zhang F, Tong J, Hu J, Zhang H, Ouyang W, Huang D, Tang Q, Liao Q. COMT gene haplotypes are closely associated with postoperative fentanyl dose in patients. Anesth Analg. 2015 Apr;120(4):933-40. doi: 10.1213/ANE.0000000000000563.
citation: Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10.