title: Innovations in the Management of Musculoskeletal Pain With Alpha-Lipoic Acid (IMPALA Trial): Study protocol for a Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Alpha-Lipoic Acid for the Treatment of Fibromyalgia Pain.
abstract: BACKGROUND
  Fibromyalgia is a common disorder characterized by chronic widespread pain, sleep disturbance, fatigue, depression, and cognitive dysfunction, resulting in substantial disability. As current analgesics provide incomplete relief and disabling side effects that aggravate fatigue and cognitive dysfunction, there is a need for new pain treatments with better efficacy and tolerability. Alpha-lipoic acid (ALA) is an antioxidant proven effective in painful diabetic neuropathy with minimal side effects.
  
  
  OBJECTIVE
  We hypothesize that this agent will provide benefits in fibromyalgia because of several similarities with neuropathic pain and also because it does not cause sedation, fatigue, or mental-slowing. To test this, we have designed a clinical trial that will assess pain, side effects, and other outcomes in participants with fibromyalgia.
  
  
  METHODS
  Using a crossover design, 24 adults with fibromyalgia will be randomly allocated to 1 of the 2 sequences of ALA and placebo. Participants will take capsules containing ALA or placebo for 4 weeks followed by a 1-week washout followed by a second 4-week treatment and 1-week washout period. ALA (or matching placebo) capsules will be titrated to 1800 mg/day over each 4-week period. The primary outcome will be mean daily pain intensity (0-10) during week 4 of each period. Secondary outcomes, assessed during week 4 of each period, will include global improvement, adverse events, mood, and quality of life.
  
  
  RESULTS
  This trial was registered in the International Standard Randomized Controlled Trial registry March 15, 2016 (Number ISRCTN58259979), and it attained ethics approval on December 3, 2016 (Queen's University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-287-15). The recruitment started in February 2017.
  
  
  CONCLUSIONS
  This trial will provide evidence for the efficacy of ALA in fibromyalgia.
  
  
  BACKGROUND
  International Standard Randomized Controlled Trial Number (ISRCTN): 58259979; www.isrctn.com/ISRCTN58259979 (Archived by WebCite at http://www.webcitation.org/6og9JdiyZ).
authors.affiliation: Queen's University, Kingston, ON, Canada.
authors.forename: Ian
authors.identifier: http://orcid.org/0000-0002-5293-8792
authors.initials: I
authors.lastname: Gilron
authors.affiliation: Queen's University, Kingston, ON, Canada.
authors.forename: Dongsheng
authors.identifier: http://orcid.org/0000-0003-4842-2184
authors.initials: D
authors.lastname: Tu
authors.affiliation: Queen's University, Kingston, ON, Canada.
authors.forename: Ronald
authors.identifier: http://orcid.org/0000-0002-9070-2510
authors.initials: R
authors.lastname: Holden
authors.affiliation: Queen's University, Kingston, ON, Canada.
authors.forename: Tanveer
authors.identifier: http://orcid.org/0000-0001-8738-9394
authors.initials: T
authors.lastname: Towheed
authors.affiliation: Heinrich Heine University, Dusseldorf, Germany.
authors.forename: Dan
authors.identifier: http://orcid.org/0000-0001-8956-3552
authors.initials: D
authors.lastname: Ziegler
authors.affiliation: Queen's University, Kingston, ON, Canada.
authors.forename: Louie
authors.identifier: http://orcid.org/0000-0002-3190-6361
authors.initials: L
authors.lastname: Wang
authors.affiliation: Queen's University, Kingston, ON, Canada.
authors.forename: Roumen
authors.identifier: http://orcid.org/0000-0001-6884-171X
authors.initials: R
authors.lastname: Milev
authors.affiliation: Kingston General Hospital, Kingston, ON, Canada.
authors.forename: Christopher
authors.identifier: http://orcid.org/0000-0002-5373-2964
authors.initials: C
authors.lastname: Gray
keywords: alpha-lipoic acid; antioxidants; fibromyalgia; pain