Contribution of COMT Haplotypes in Propranolol Analgesic Efficacy for Treating Post-surgical Pain After Laparoscopic Hemicolectomy
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Enrollment
- 10
- Locations
- 2
- Primary Endpoint
- Total morphine delivered by IV-PCA
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
IV-PCA morphine + Placebo PO
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.
Intervention: IV-PCA morphine (Drug)
IV-PCA morphine + Placebo PO
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.
Intervention: Placebo PO (Drug)
IV-PCA morphine + Placebo PO
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.
Intervention: Quantitative Sensory Testing (QST) (Procedure)
IV-PCA morphine + Placebo PO
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.
Intervention: Psychometric assessment (Other)
IV-PCA morphine + Placebo PO
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.
Intervention: COMT-haplotypes (Genetic)
IV-PCA morphine + Propranolol PO
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.
Intervention: Propranolol PO (Drug)
IV-PCA morphine + Propranolol PO
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.
Intervention: IV-PCA morphine (Drug)
IV-PCA morphine + Propranolol PO
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.
Intervention: Quantitative Sensory Testing (QST) (Procedure)
IV-PCA morphine + Propranolol PO
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.
Intervention: Psychometric assessment (Other)
IV-PCA morphine + Propranolol PO
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.
Intervention: COMT-haplotypes (Genetic)
Outcomes
Primary Outcomes
Total morphine delivered by IV-PCA
Time Frame: Day II Post-op
Secondary Outcomes
- 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)
- Somatization, depression and anxiety by SCL-90-R subscales(Pre-op visit)
- Sleep quality by PSQI(Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op)
- Post-operative Chronic Pain by PQRS(Pre-op visit, Day II Post-op, 4 weeks Post-op, 3 months Post-op, 6 months Post-op)
- Pain quality by sfMGPQ(one evaluation during the first 8 Post-op hours, Day I Post-op, Day II 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)
Investigators
Franco Carli
Professor of Anesthesia
McGill University Health Centre/Research Institute of the McGill University Health Centre