Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain (PRO_GENE_POP)

McGill University

Status and phase: Terminated; Phase 2

Conditions: Postoperative Pain

Treatments: Drug: IV-PCA morphine; Drug: Placebo PO; Other: Psychometric assessment; Procedure: Quantitative Sensory Testing (QST); Genetic: COMT-haplotypes; Drug: Propranolol PO

Study type: Interventional

Funder types: Other

Identifiers

NCT02511483

15-169-MUHC

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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10 participants in 2 patient groups, including a placebo group

IV-PCA morphine + Placebo PO

Placebo Comparator group

Description:

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.

Treatment:

Genetic: COMT-haplotypes

Procedure: Quantitative Sensory Testing (QST)

Other: Psychometric assessment

Drug: Placebo PO

Drug: IV-PCA morphine

IV-PCA morphine + Propranolol PO

Experimental group

Description:

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.

Treatment:

Genetic: COMT-haplotypes

Drug: Propranolol PO

Procedure: Quantitative Sensory Testing (QST)

Other: Psychometric assessment

Drug: IV-PCA morphine