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

Primary Purpose

Postoperative Pain

Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Propranolol PO
IV-PCA morphine
Placebo PO
Quantitative Sensory Testing (QST)
Psychometric assessment
COMT-haplotypes
Sponsored by
McGill University Health Centre/Research Institute of the McGill University Health Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postoperative Pain focused on measuring COMT, Beta-blocker, Hemicolectomy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Montreal General Hospital
  • Royal Victoria Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

IV-PCA morphine + Placebo PO

IV-PCA morphine + Propranolol PO

Arm 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.

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.

Outcomes

Primary Outcome Measures

Total morphine delivered by IV-PCA

Secondary Outcome Measures

Pressure Pain Threshold by digital pressure algometer
Hyperalgesia test by von Frey hair
Pain measured by the Numerical pain Rating Scale
Somatization, depression and anxiety by SCL-90-R subscales
Symptom Checklist 90 Revised (SCL-90-R) subscales for somatization, depression and anxiety
Sleep quality by PSQI
Pittsburgh Sleep Questionnaire Index (PSQI)
Pain quality by sfMGPQ
Short Form-McGill Pain Questionnaire
Post-operative Chronic Pain by PQRS
Post-operative Quality of Recovery Scale (PQRS)

Full Information

First Posted
July 23, 2015
Last Updated
September 24, 2021
Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre
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1. Study Identification

Unique Protocol Identification Number
NCT02511483
Brief Title
Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain
Acronym
PRO_GENE_POP
Official Title
Contribution of COMT Haplotypes in Propranolol Analgesic Efficacy for Treating Post-surgical Pain After Laparoscopic Hemicolectomy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
Difficulty with recruitment
Study Start Date
May 18, 2015 (Actual)
Primary Completion Date
November 12, 2016 (Actual)
Study Completion Date
November 12, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Pain
Keywords
COMT, Beta-blocker, Hemicolectomy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV-PCA morphine + Placebo PO
Arm Type
Placebo Comparator
Arm 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.
Arm Title
IV-PCA morphine + Propranolol PO
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Propranolol PO
Other Intervention Name(s)
CAS No 525-66-6, DINs: 00740675, 00496480
Intervention Description
20 mg PO BID Day of Surgery, 30 mg PO BID Day I and Day II post-op.
Intervention Type
Drug
Intervention Name(s)
IV-PCA morphine
Other Intervention Name(s)
Patient controlled Analgesia with intravenous morphine
Intervention Description
Morphine delivered via IV-PCA pump for 48 hours after surgery with standard program: bolus 1 mg, lock out 7 minutes, no background infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo PO
Other Intervention Name(s)
tablet containing microcrystalline cellulose
Intervention Description
Placebo tablets administered with the same schedule of Propranolol tablets
Intervention Type
Procedure
Intervention Name(s)
Quantitative Sensory Testing (QST)
Other Intervention Name(s)
Pressure Pain Threshold and Hyperalgesia test
Intervention Description
Assessment of PPT (Pressure Pain Threshold) by pressure algometer and assessment of the post-op area of hyperalgesia by von Frey hair no. 16.
Intervention Type
Other
Intervention Name(s)
Psychometric assessment
Other Intervention Name(s)
PSQI, sfMGPQ, SCL-90-R, PQRS
Intervention Description
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)
Intervention Type
Genetic
Intervention Name(s)
COMT-haplotypes
Other Intervention Name(s)
HPS, APS, LPS
Intervention Description
Assessing of High Pain Sensitivity (HPS), Average Pain Sensitivity (APS) and Low Pain Sensitivity (LPS) haplotypes for COMT by genotyping peripheral blood samples.
Primary Outcome Measure Information:
Title
Total morphine delivered by IV-PCA
Time Frame
Day II Post-op
Secondary Outcome Measure Information:
Title
Pressure Pain Threshold by digital pressure algometer
Time Frame
Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Title
Hyperalgesia test by von Frey hair
Time Frame
Pre-op visit, Day I Post-op, Day II Post-op, four weeks Post-op
Title
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
Title
Somatization, depression and anxiety by SCL-90-R subscales
Description
Symptom Checklist 90 Revised (SCL-90-R) subscales for somatization, depression and anxiety
Time Frame
Pre-op visit
Title
Sleep quality by PSQI
Description
Pittsburgh Sleep Questionnaire Index (PSQI)
Time Frame
Pre-op visit, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
Title
Pain quality by sfMGPQ
Description
Short Form-McGill Pain Questionnaire
Time Frame
one evaluation during the first 8 Post-op hours, Day I Post-op, Day II Post-op
Title
Post-operative Chronic Pain by PQRS
Description
Post-operative Quality of Recovery Scale (PQRS)
Time Frame
Pre-op visit, Day II Post-op, 4 weeks Post-op, 3 months Post-op, 6 months Post-op
Other Pre-specified Outcome Measures:
Title
COMT-haplotypes by blood sampling genotyping
Time Frame
Pre-op, Day III Post-op, 4 weeks Post-op

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luda Diatchenko, Professor
Organizational Affiliation
Anesthesia Department McGill University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montreal General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3G 1A4
Country
Canada
Facility Name
Royal Victoria Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada

12. IPD Sharing Statement

Citations:
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25084070
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Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain

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