Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain

Study Overview
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Brief Summary
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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.

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

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Propranolol PO
* Drug: IV-PCA morphine
* Drug: Placebo PO
* Procedure: Quantitative Sensory Testing (QST)
* Other: Psychometric assessment
* Genetic: COMT-haplotypes


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: IV-PCA morphine + Placebo PO<br>Pain control after surgery will be performed through IV-PCA morphine. Placebo will be administered with the same schedule of Propranolol in the experimental arm. Parallel evaluation of Quantitative Sensory Testing (QST), Psychometric assessment and COMT-haplotypes will be included along the trial. | Drug: IV-PCA morphine<br>* Morphine delivered via IV-PCA pump for 48 hours after surgery with standard program: bolus 1 mg, lock out 7 minutes, no background infusion.<br>* Other names: Patient controlled Analgesia with intravenous morphine;Drug: Placebo PO<br>* Placebo tablets administered with the same schedule of Propranolol tablets<br>* Other names: tablet containing microcrystalline cellulose;Procedure: Quantitative Sensory Testing (QST)<br>* Assessment of PPT (Pressure Pain Threshold) by pressure algometer and assessment of the post-op area of hyperalgesia by von Frey hair no. 16.<br>* Other names: Pressure Pain Threshold and Hyperalgesia test;Other: Psychometric assessment<br>* 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)<br>* Other names: PSQI, sfMGPQ, SCL-90-R, PQRS;Genetic: COMT-haplotypes<br>* Assessing of High Pain Sensitivity (HPS), Average Pain Sensitivity (APS) and Low Pain Sensitivity (LPS) haplotypes for COMT by genotyping peripheral blood samples.<br>* Other names: HPS, APS, LPS;|
| Experimental: IV-PCA morphine + Propranolol PO<br>The morning of the surgery a dose of Propranolol 20 mg PO will be administered. After surgery pain control will be performed with IV-PCA morphine; in addition a second dose of Propranolol 20 mg PO will be administered . During the first and second postoperative day Propranolol 30 mg PO (BID) will be administered. Parallel assessment of Quantitative Sensory Testing (QST), Psychometric assessment and COMT-haplotypes will be included along the trial. | Drug: Propranolol PO<br>* 20 mg PO BID Day of Surgery, 30 mg PO BID Day I and Day II post-op.<br>* Other names: CAS No 525-66-6, DINs: 00740675, 00496480;Drug: IV-PCA morphine<br>* Morphine delivered via IV-PCA pump for 48 hours after surgery with standard program: bolus 1 mg, lock out 7 minutes, no background infusion.<br>* Other names: Patient controlled Analgesia with intravenous morphine;Procedure: Quantitative Sensory Testing (QST)<br>* Assessment of PPT (Pressure Pain Threshold) by pressure algometer and assessment of the post-op area of hyperalgesia by von Frey hair no. 16.<br>* Other names: Pressure Pain Threshold and Hyperalgesia test;Other: Psychometric assessment<br>* 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)<br>* Other names: PSQI, sfMGPQ, SCL-90-R, PQRS;Genetic: COMT-haplotypes<br>* Assessing of High Pain Sensitivity (HPS), Average Pain Sensitivity (APS) and Low Pain Sensitivity (LPS) haplotypes for COMT by genotyping peripheral blood samples.<br>* Other names: HPS, APS, LPS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total morphine delivered by IV-PCA |  | Day II Post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure Pain Threshold by digital pressure algometer |  | Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op | 
| Hyperalgesia test by von Frey hair |  | Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op | 
| 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 | 
| 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 | 
| Sleep quality by PSQI | Pittsburgh Sleep Questionnaire Index (PSQI) | Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COMT, Beta-blocker, Hemicolectomy