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

September 24, 2021 updated by: Franco Carli, McGill University Health Centre/Research Institute of the McGill University Health Centre

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

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 Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3G 1A4
        • Montreal General Hospital
      • Montreal, Quebec, Canada, H4A 3J1
        • Royal Victoria Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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.
Drug: 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.
Other Names:
  • Patient controlled Analgesia with intravenous morphine
Drug: Placebo PO
Placebo tablets administered with the same schedule of Propranolol tablets
Other Names:
  • tablet containing microcrystalline cellulose
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 Names:
  • Pressure Pain Threshold and Hyperalgesia test
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)
Other Names:
  • PSQI, sfMGPQ, SCL-90-R, PQRS
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.
Other Names:
  • HPS, APS, LPS
Experimental: 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.
Drug: 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.
Other Names:
  • Patient controlled Analgesia with intravenous morphine
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 Names:
  • Pressure Pain Threshold and Hyperalgesia test
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)
Other Names:
  • PSQI, sfMGPQ, SCL-90-R, PQRS
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.
Other Names:
  • HPS, APS, LPS
Drug: Propranolol PO
20 mg PO BID Day of Surgery, 30 mg PO BID Day I and Day II post-op.
Other Names:
  • CAS No 525-66-6, DINs: 00740675, 00496480

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pressure Pain Threshold by digital pressure algometer
Time Frame: Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Hyperalgesia test by von Frey hair
Time Frame: Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Pain measured by the Numerical pain Rating Scale
Time Frame: 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
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
Time Frame: Pre-op visit
Symptom Checklist 90 Revised (SCL-90-R) subscales for somatization, depression and anxiety
Pre-op visit
Sleep quality by PSQI
Time Frame: Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
Pittsburgh Sleep Questionnaire Index (PSQI)
Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
Pain quality by sfMGPQ
Time Frame: one evaluation during the first 8 Post-op hours, Day I Post-op, Day II Post-op
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
Time Frame: Pre-op visit, Day II Post-op, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
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

Other Outcome Measures

Outcome Measure
Time Frame
COMT-haplotypes by blood sampling genotyping
Time Frame: Pre-op, Day III Post-op, 4 weeks Post-op
Pre-op, Day III Post-op, 4 weeks Post-op

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

Investigators

  • Principal Investigator: Luda Diatchenko, Professor, Anesthesia Department McGill University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 18, 2015

Primary Completion (Actual)

November 12, 2016

Study Completion (Actual)

November 12, 2016

Study Registration Dates

First Submitted

July 23, 2015

First Submitted That Met QC Criteria

July 27, 2015

First Posted (Estimate)

July 30, 2015

Study Record Updates

Last Update Posted (Actual)

September 28, 2021

Last Update Submitted That Met QC Criteria

September 24, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-169-MUHC

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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