Leader(s): Ian GilronLuda DiatchenkoNader Ghasemlou,  Elizabeth Vandenkerkhof and Scott Duggan
Institution(s): Queen’s UniversityMcGill UniversityUniversity of Manitoba
Other Members: Dongsheng Tu, Ronald Holden, Roumen Milev, Alan
Jackson, Tanveer Towheed

Why was the study done?
Chronic pain, including neuropathic pain (nerve pain),affects 1 in 3 Canadians and costs approximately $650 billion/year in North America. Currenttherapies have limitedefficacy (effectiveness) and can cause adverse effects that limit the dose that patients can tolerate.   

Using combinations of medications to treat fibromyalgia hasshown potential toimprove pain relief and quality of life and reducehealthcare utilization. Today, more than half of fibromyalgia patients receive 2 or more analgesics (pain medications) butcombination use is based on little evidence.Research is urgently needed to identify safer (and more effective) combinations of medications for fibromyalgia. 

How was the study done?
Ourprevious CIHR chronic pain trialsshowed that analgesics and sedatives (medications that can cause drowsiness) are more effective than analgesics alone.    
These combinations were as follows: 

  • morphine and gabapentin  

  • gabapentin and nortriptyline 

  • nortriptyline and morphine  

  • pregabalin and duloxetine  

However, the benefits were limited  because doses had to be reduced duringcombination therapy toensure safety and tolerability (and limit adverse effects). 
Thus, we wanted to determine whether pain relieving combinations that contain at least one non-sedatingagent would reduce pain without causing undue adverse effects. 

We were particularly interested in two medications (or agents) to treat fibromyalgia.

Pregabalin (PGB) is asedating anticonvulsant (anti seizure medication) proven effective for fibromyalgia.  The antioxidant, alpha-lipoic acid (ALA) is currently the only non-sedating agent proveneffective for chronic neuropathic pain and also shows promise for the treatmentof fibromyalgia.

What were the study results?
Wewill conduct a randomized controlled clinical trial to compare a PGB-ALAcombination to single drug therapy for fibromyalgia.  The study will include 55 people diagnosed with fibromyalgia and will run until November 2020. 

Recent Updates:
Upon finalization of trial analysis and reporting, findings will be submitted for publication and knowledge translation activities will commence. 
Last updated: January 2021

Selected Publications:
  • Park R, Ho AM, Pickering G, Arendt-Nielsen L, Mohiuddin M, Gilron I. Efficacy and Safety of Magnesium for the Management of Chronic Pain in Adults: A Systematic Review. Anesth Analg. 2020 Feb 10. doi: 10.1213/ANE.0000000000004673. [Epub ahead of print] PubMed PMID: 32049671.
  • Camiré D, Erb J, Kehlet H, Brennan T, Gilron I. Movement-Evoked Pain Versus Pain at Rest in Postsurgical Clinical Trials and Meta-Analyses: Protocol for a Follow-Up Systematic Review. JMIR Res Protoc. 2020 Jan 22;9(1):e15309. doi: 10.2196/15309. PubMed PMID: 32012101; PubMed Central PMCID: PMC7003115.
  • Park R, Mohiuddin M, Poulin P, Salomons T, Edwards R, Nathan H, Haley C, Gilron I. Interactions between analgesic drug therapy and mindfulness-based interventions for chronic pain in adults: protocol for a systematic scoping review. Pain Rep. 2019 Nov 21;4(6):e793. doi: 10.1097/PR9.0000000000000793. eCollection 2019 Nov-Dec. PubMed PMID: 31984298; PubMed Central PMCID:PMC6903347.
  • Mohiuddin MM, Mizubuti GB, Haroutounian S, Smith SM, Rice ASC, Campbell F, Park R, Gilron I. Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Medical Cannabis and Cannabis-based Medicines for Chronic Noncancer Pain: A Systematic Review. Clin J Pain. 2020 Apr;36(4):302-319. doi: 10.1097/AJP.0000000000000807. PubMed PMID: 31977375.
  • Gilron I, Blyth FM, Degenhardt L, Di Forti M, Eccleston C, Haroutounian S, Moore A, Rice ASC, Wallace M. Risks of harm with cannabinoids, cannabis, and cannabis-based medicine for pain management relevant to patients receiving pain treatment: protocol for an overview of systematic reviews. Pain Rep. 2019 May 29;4(3):e742. doi: 10.1097/PR9.0000000000000742. eCollection 2019 May-Jun. Review. PubMed PMID: 31583357; PubMed Central PMCID: PMC6749892.
  • Gilron I, Blyth F, Smith BH. Translating clinical trials into improved real-world management of pain: convergence of translational, population-based, and primary care research. Pain. 2020 Jan;161(1):36-42. doi: 10.1097/j.pain.0000000000001684. PubMed PMID: 31433350.
  • Marshall AS, Silva JR, Bannerman CA, Gilron I, Ghasemlou N. Skin-Resident γδ T Cells Exhibit Site-Specific Morphology and Activation States. J Immunol Res. 2019 Jan 6;2019:9020234. doi: 10.1155/2019/9020234. eCollection 2019. PubMed PMID: 30723751; PubMed Central PMCID: PMC6339708.
  • Mohiuddin MM, Mizubuti G, Haroutounian S, Smith S, Campbell F, Park R, Gilron I. Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Cannabinoids for Chronic Pain: Protocol for a Systematic Review. JMIR Res Protoc. 2019 Jan 28;8(1):e11637. doi: 10.2196/11637. PubMed PMID: 30688655; PubMed Central PMCID: PMC6369421.
  • Park R, Ho AM, Pickering G, Arendt-Nielsen L, Mohiuddin M, Gilron I. Magnesium for the Management of Chronic Noncancer Pain in Adults: Protocol for a Systematic Review. JMIR Res Protoc. 2019 Jan 11;8(1):e11654. doi: 10.2196/11654. PubMed PMID: 30635260; PubMed Central PMCID: PMC6330196.
  • Gilron I, Tu D, Holden R, Towheed T, Vandenkerkhof E, Milev R. Combination Analgesic Development for Enhanced Clinical Efficacy (CADENCE Trial): Study Protocol for a Double-Blind, Randomized, Placebo-Controlled Crossover Trial of an Alpha-Lipoic Acid - Pregabalin Combination for the Treatment of Fibromyalgia Pain. JMIR Res Protoc. 2017 Aug 4;6(8):e154. doi: 10.2196/resprot.8001. PubMed PMID: 28778847; PubMed Central PMCID: PMC5705061.