Genetic Predictors of Analgesic Efficacy of Propranolol for Treating Postoperative Pain

NCT ID: NCT02511483

Last Updated: 2021-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-18

Study Completion Date

2016-11-12

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.

Detailed Description

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Conditions

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Postoperative Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

IV-PCA morphine

Intervention Type DRUG

Morphine delivered via IV-PCA pump for 48 hours after surgery with standard program: bolus 1 mg, lock out 7 minutes, no background infusion.

Placebo PO

Intervention Type DRUG

Placebo tablets administered with the same schedule of Propranolol tablets

Quantitative Sensory Testing (QST)

Intervention Type PROCEDURE

Assessment of PPT (Pressure Pain Threshold) by pressure algometer and assessment of the post-op area of hyperalgesia by von Frey hair no. 16.

Psychometric assessment

Intervention Type OTHER

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)

COMT-haplotypes

Intervention Type GENETIC

Assessing of High Pain Sensitivity (HPS), Average Pain Sensitivity (APS) and Low Pain Sensitivity (LPS) haplotypes for COMT by genotyping peripheral blood samples.

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.

Group Type EXPERIMENTAL

Propranolol PO

Intervention Type DRUG

20 mg PO BID Day of Surgery, 30 mg PO BID Day I and Day II post-op.

IV-PCA morphine

Intervention Type DRUG

Morphine delivered via IV-PCA pump for 48 hours after surgery with standard program: bolus 1 mg, lock out 7 minutes, no background infusion.

Quantitative Sensory Testing (QST)

Intervention Type PROCEDURE

Assessment of PPT (Pressure Pain Threshold) by pressure algometer and assessment of the post-op area of hyperalgesia by von Frey hair no. 16.

Psychometric assessment

Intervention Type OTHER

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)

COMT-haplotypes

Intervention Type GENETIC

Assessing of High Pain Sensitivity (HPS), Average Pain Sensitivity (APS) and Low Pain Sensitivity (LPS) haplotypes for COMT by genotyping peripheral blood samples.

Interventions

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Propranolol PO

20 mg PO BID Day of Surgery, 30 mg PO BID Day I and Day II post-op.

Intervention Type 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.

Intervention Type DRUG

Placebo PO

Placebo tablets administered with the same schedule of Propranolol tablets

Intervention Type DRUG

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.

Intervention Type PROCEDURE

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)

Intervention Type OTHER

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.

Intervention Type GENETIC

Other Intervention Names

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CAS No 525-66-6, DINs: 00740675, 00496480 Patient controlled Analgesia with intravenous morphine tablet containing microcrystalline cellulose Pressure Pain Threshold and Hyperalgesia test PSQI, sfMGPQ, SCL-90-R, PQRS HPS, APS, LPS

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

OTHER

Sponsor Role lead

Responsible Party

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Franco Carli

Professor of Anesthesia

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Luda Diatchenko, Professor

Role: PRINCIPAL_INVESTIGATOR

Anesthesia Department McGill University

Locations

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Montreal General Hospital

Montreal, Quebec, Canada

Site Status

Royal Victoria Hospital

Montreal, Quebec, Canada

Site Status

Countries

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Canada

References

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Orrey DC, Halawa OI, Bortsov AV, Shupp JW, Jones SW, Haith LR, Hoskins JM, Jordan MH, Bangdiwala SI, Roane BR, Platts-Mills TF, Holmes JH, Hwang J, Cairns BA, McLean SA. Results of a pilot multicenter genotype-based randomized placebo-controlled trial of propranolol to reduce pain after major thermal burn injury. Clin J Pain. 2015 Jan;31(1):21-9. doi: 10.1097/AJP.0000000000000086.

Reference Type BACKGROUND
PMID: 25084070 (View on PubMed)

Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab.

Reference Type BACKGROUND
PMID: 20216107 (View on PubMed)

Zaugg M, Tagliente T, Lucchinetti E, Jacobs E, Krol M, Bodian C, Reich DL, Silverstein JH. Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology. 1999 Dec;91(6):1674-86. doi: 10.1097/00000542-199912000-00020.

Reference Type BACKGROUND
PMID: 10598610 (View on PubMed)

Schweinhardt P, Abulhasan YB, Koeva V, Balderi T, Kim DJ, Alhujairi M, Carli F. Effects of intravenous propranolol on heat pain sensitivity in healthy men. Eur J Pain. 2013 May;17(5):704-13. doi: 10.1002/j.1532-2149.2012.00231.x. Epub 2012 Oct 16.

Reference Type BACKGROUND
PMID: 23070986 (View on PubMed)

Pranevicius M, Pranevicius O. Non-opioid anesthesia with esmolol avoids opioid-induced hyperalgesia and reduces fentanyl requirement after laparoscopy. Anesth Analg. 2009 Mar;108(3):1048. doi: 10.1213/ane.0b013e3181938f3f. No abstract available.

Reference Type BACKGROUND
PMID: 19224829 (View on PubMed)

Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth. 2004 Dec;93(6):799-805. doi: 10.1093/bja/aeh268. Epub 2004 Sep 17.

Reference Type BACKGROUND
PMID: 15377583 (View on PubMed)

Chen YW, Chu CC, Chen YC, Hung CH, Wang JJ. Propranolol elicits cutaneous analgesia against skin nociceptive stimuli in rats. Neurosci Lett. 2012 Aug 30;524(2):129-32. doi: 10.1016/j.neulet.2012.07.036. Epub 2012 Jul 26.

Reference Type BACKGROUND
PMID: 22842397 (View on PubMed)

Zhang F, Tong J, Hu J, Zhang H, Ouyang W, Huang D, Tang Q, Liao Q. COMT gene haplotypes are closely associated with postoperative fentanyl dose in patients. Anesth Analg. 2015 Apr;120(4):933-40. doi: 10.1213/ANE.0000000000000563.

Reference Type BACKGROUND
PMID: 25532715 (View on PubMed)

Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10.

Reference Type BACKGROUND
PMID: 15537663 (View on PubMed)

Other Identifiers

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15-169-MUHC

Identifier Type: -

Identifier Source: org_study_id

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