Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain

Postoperative Pain Clinical Trial

— PRO_GENE_POP  

Official title:

Contribution of COMT Haplotypes in Propranolol Analgesic Efficacy for Treating Post-surgical Pain After Laparoscopic Hemicolectomy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02511483
• Other study ID #: 15-169-MUHC
• Status: Terminated
• Phase: Phase 2
• Start date: May 18, 2015
• Est. completion date: November 12, 2016

Study information

• Verified date: September 2021
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: November 12, 2016
• Est. primary completion date: November 12, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Propranolol PO
20 mg PO BID Day of Surgery, 30 mg PO BID Day I and Day II post-op.
• IV-PCA morphine
Morphine delivered via IV-PCA pump for 48 hours after surgery with standard program: bolus 1 mg, lock out 7 minutes, no background infusion.
• Placebo PO
Placebo tablets administered with the same schedule of Propranolol tablets

Procedure:
• Quantitative Sensory Testing (QST)
Assessment of PPT (Pressure Pain Threshold) by pressure algometer and assessment of the post-op area of hyperalgesia by von Frey hair no. 16.

Other:
• Psychometric assessment
Questionnaires assessing for sleep quality (PSQI: Pittsburgh Sleep Quality Index), pain quality (sfMGPQ-Short Form-McGill Pain Questionnaire), somatization-depression-anxiety (SCL-90-R: Symptom Checklist 90 Revised), evolution of post-operative chronic pain (PQRS: Post-operative Quality of Recovery Scale)

Genetic:
• COMT-haplotypes
Assessing of High Pain Sensitivity (HPS), Average Pain Sensitivity (APS) and Low Pain Sensitivity (LPS) haplotypes for COMT by genotyping peripheral blood samples.

Locations

Country	Name	City	State
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre

Country where clinical trial is conducted

Canada, 

References & Publications (9)

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. — View 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. Epub 2004 Sep 17. — View 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. Epub 2004 Nov 10. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	COMT-haplotypes by blood sampling genotyping		Pre-op, Day III Post-op, 4 weeks Post-op
Primary	Total morphine delivered by IV-PCA		Day II Post-op
Secondary	Pressure Pain Threshold by digital pressure algometer		Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Secondary	Hyperalgesia test by von Frey hair		Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Secondary	Pain measured by the Numerical pain Rating Scale		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
Secondary	Somatization, depression and anxiety by SCL-90-R subscales	Symptom Checklist 90 Revised (SCL-90-R) subscales for somatization, depression and anxiety	Pre-op visit
Secondary	Sleep quality by PSQI	Pittsburgh Sleep Questionnaire Index (PSQI)	Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
Secondary	Pain quality by sfMGPQ	Short Form-McGill Pain Questionnaire	one evaluation during the first 8 Post-op hours, Day I Post-op, Day II Post-op
Secondary	Post-operative Chronic Pain by PQRS	Post-operative Quality of Recovery Scale (PQRS)	Pre-op visit, Day II Post-op, 4 weeks Post-op, 3 months Post-op, 6 months Post-op

External Links

•   Human Pain Genetic Lab