Genetic Variants Associated With Low Back Pain and Their Response to Treatment With Duloxetine or Propranolol

NCT03364075 | Terminated Phase 2

• 1 other identifier: MUHC15046
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, double-blind, placebo controlled, three period crossover clinical trial. The main purpose of this study is to determine if Chronic Low Back Pain patients presenting with either localized or widespread painful symptoms respond differently to treatment with Duloxetine or Propranolol, and if the effectiveness of treatment with these drugs can determined by the presence or absence of SNPs associated with the Serotonin receptor or Cathecol-O-MethylTransferase activity. Each treatment period will be of two weeks duration with a 1 week washout phase between treatment periods. Following a Latin square design, patients will be randomly assigned to one of six different treatment groups, starting their first treatment cycle with either Duloxetine, Propranolol or Placebo and rotating through the other treatments in the subsequent cycles. Effectiveness of treatment will be measured by means of Pain Index as the primary outcome measure, and secondary outcome measures will include Pressure Pain Threshold and the Pain Disability Index, Perceived Stress Scale, Symptom Checklist -90R and the Patient's Global Impression of Change questionnaires.

Conditions

Low Back Pain

Outcome Measures

Primary Outcomes (1)

• pain index

  Average pain intensity multiplied by percentage of time in pain in the waking day.

  Difference between the average pain index on the first three days of treatment compared to the last three days of the 14 day treatment cycle

Study Arms (3)

Duloxetine Treatment

ACTIVE COMPARATOR

patients treated with Duloxetine

Drug: Duloxetine; Genetic: Genotype for SNPs associated to Serotonin and COMT; Drug: Placebo Treatment

Propranolol Treatment

ACTIVE COMPARATOR

patients treated with Propranolol

Drug: Propranolol; Genetic: Genotype for SNPs associated to Serotonin and COMT; Drug: Placebo Treatment

Placebo Treatment

PLACEBO COMPARATOR

patients treated with placebo

Drug: Duloxetine; Drug: Propranolol

Interventions

Duloxetine DRUG

30 mg for seven days, then increased to 60 mg for seven days

Also known as: Cymbalta

Duloxetine Treatment; Placebo Treatment

Propranolol DRUG

40 mg for seven days, then increase to 60 mg for seven days

Also known as: TevaPropranolol

Placebo Treatment; Propranolol Treatment

Genotype for SNPs associated to Serotonin and COMT GENETIC

DNA and RNA extraction from blood samples to identify genetic variants associated to pain pathways

Duloxetine Treatment; Propranolol Treatment

Placebo Treatment DRUG

1 capsule BID for two weeks

Duloxetine Treatment; Propranolol Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Uncontrolled medical or psychiatric conditions.
• History of major depressive disorder, psychotic disorder or schizophrenia, and/or manic episodes within the past year.
• Pregnancy and/or breast-feeding. Patients who are unsure of their status will also be excluded from participating
• Pain due to cancer.
• Disability compensation or litigation.
• Neurologic signs of lumbosacral radiculopathy within the past 6 months: lower extremity muscle weakness/sensory loss in a dermatomal distribution, abnormal deep tendon reflexes.
• Radiographic and/or electrophysiology evidence of radicular compression in the past 6 months.
• Clinical signs of lumbar stenosis within the past 6 months: numbness, weakness, and/or discomfort radiating from the spine down to the buttocks and legs while walking or in prolonged standing and relieved with sitting or lying.
• Clinical signs of back pain that requires an urgent/alternative intervention: new onset bowel/bladder incontinence, saddle anaesthesia, foot drop, unexplained weight loss, fever.
• Radiographic evidence of spinal stenosis, high-grade spondylolisthesis (grade 3 or 4), acute spinal fracture, tumour, abscess or acute pathology in the low back/abdominal area in the past 6 months.
• Low back surgery (lumbosacral spine) within the past 12 months, or history of more than 1 low back surgery.
• Minimally invasive procedures aimed to reduce pain in the lumbosacral area within the past month (Medial Branch Blocks/Ablations, Epidural Steroid Injections, Trigger point injections, Sacroiliac Joint Injections, Greater Trochanteric/Acetabulofemoral Joint Injections).
• Known hypersensitivity to Beta Blockers or SNRIs.
• Currently taking SNRIs, Beta Blockers, Opioids at a daily dose superior to 30mg of Morphine Oral Equivalent, Tricyclic Antidepressants, Methylene Blue, Linezolid, Monoamine Oxidase Inhibitors (such as Selegiline, Isoniazid, Procarbazine), Thioridazine, CYP1A2 inhibitors (Fluvoxamine, Verapamil, Cimetidine, Fluoroquinolone antibiotics such as Ciprofloxacin).
• Active alcoholism within the past 6 months.

Sponsors & Collaborators

• Mark Ware: lead

Study Sites (1)

Centre for Innovative Medicine - McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (11)

• Lim KL, Jacobs P, Klarenbach S. A population-based analysis of healthcare utilization of persons with back disorders: results from the Canadian Community Health Survey 2000-2001. Spine (Phila Pa 1976). 2006 Jan 15;31(2):212-8. doi: 10.1097/01.brs.0000194773.10461.9f.

  PMID: 16418643 BACKGROUND

• Von Korff M, Crane P, Lane M, Miglioretti DL, Simon G, Saunders K, Stang P, Brandenburg N, Kessler R. Chronic spinal pain and physical-mental comorbidity in the United States: results from the national comorbidity survey replication. Pain. 2005 Feb;113(3):331-339. doi: 10.1016/j.pain.2004.11.010.

  PMID: 15661441 BACKGROUND

• Coyte PC, Asche CV, Croxford R, Chan B. The economic cost of musculoskeletal disorders in Canada. Arthritis Care Res. 1998 Oct;11(5):315-25. doi: 10.1002/art.1790110503.

  PMID: 9830876 BACKGROUND

• Koes BW, van Tulder M, Lin CW, Macedo LG, McAuley J, Maher C. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J. 2010 Dec;19(12):2075-94. doi: 10.1007/s00586-010-1502-y. Epub 2010 Jul 3.

  PMID: 20602122 BACKGROUND

• Fairbank J, Gwilym SE, France JC, Daffner SD, Dettori J, Hermsmeyer J, Andersson G. The role of classification of chronic low back pain. Spine (Phila Pa 1976). 2011 Oct 1;36(21 Suppl):S19-42. doi: 10.1097/BRS.0b013e31822ef72c.

  PMID: 21952188 BACKGROUND

• Thomas E, Silman AJ, Croft PR, Papageorgiou AC, Jayson MI, Macfarlane GJ. Predicting who develops chronic low back pain in primary care: a prospective study. BMJ. 1999 Jun 19;318(7199):1662-7. doi: 10.1136/bmj.318.7199.1662.

  PMID: 10373170 BACKGROUND

• Natvig B, Bruusgaard D, Eriksen W. Localized low back pain and low back pain as part of widespread musculoskeletal pain: two different disorders? A cross-sectional population study. J Rehabil Med. 2001 Jan;33(1):21-5. doi: 10.1080/165019701300006498.

  PMID: 11480465 BACKGROUND

• Slade GD, Smith SB, Zaykin DV, Tchivileva IE, Gibson DG, Yuryev A, Mazo I, Bair E, Fillingim R, Ohrbach R, Greenspan J, Maixner W, Diatchenko L. Facial pain with localized and widespread manifestations: separate pathways of vulnerability. Pain. 2013 Nov;154(11):2335-2343. doi: 10.1016/j.pain.2013.07.009. Epub 2013 Jul 16.

  PMID: 23867732 BACKGROUND

• Wiesinger B, Malker H, Englund E, Wanman A. Back pain in relation to musculoskeletal disorders in the jaw-face: a matched case-control study. Pain. 2007 Oct;131(3):311-319. doi: 10.1016/j.pain.2007.03.018. Epub 2007 Apr 24.

  PMID: 17459585 BACKGROUND

• Millan MJ. Descending control of pain. Prog Neurobiol. 2002 Apr;66(6):355-474. doi: 10.1016/s0301-0082(02)00009-6.

  PMID: 12034378 BACKGROUND

• 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.

  PMID: 20216107 BACKGROUND

MeSH Terms

Conditions

Low Back Pain

Interventions

Duloxetine Hydrochloride; Propranolol; Genotype

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Genetic Phenomena

Study Officials

• Mark Ware, MBBS MRCP

  Director of Clinical Research Alan Edwards Pain Management Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: BA, MBBS, MRCP, MSc

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: December 6, 2017
• Study Start: September 1, 2017
• Primary Completion: May 31, 2018
• Study Completion: May 31, 2018
• Last Updated: August 28, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)