PMID- 28778847 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1929-0748 (Print) IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 6 IP - 8 DP - 2017 Aug 4 TI - 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. PG - e154 LID - 10.2196/resprot.8001 [doi] LID - e154 AB - BACKGROUND: Fibromyalgia is a clinical disorder commonly presenting with chronic widespread pain as well as sleep disturbance, fatigue, depression, and cognitive dysfunction. There is an urgent need for treatment strategies that provide better pain relief and fewer adverse effects (AEs). Efforts to develop rational combinations of specific fibromyalgia treatments have demonstrated potential for measurable improvements in pain relief, quality of life, and health care utilization. More than half of fibromyalgia patients receive 2 or more analgesics but current combination use is based on limited evidence. As an early proof-of-concept project from the Canadian Institutes of Health Research-Strategy on Patient-Oriented Research Chronic Pain Network, this trial protocol is expected to advance the field by rigorously evaluating a new treatment combination for fibromyalgia. OBJECTIVE: We will test the hypothesis that analgesic combinations containing at least one nonsedating agent would be as safe but more effective than either monotherapy because of additive pain relief without increasing overall AEs. Pregabalin (PGB), a sedating anticonvulsant, is proven effective for fibromyalgia, and the antioxidant, alpha-lipoic acid (ALA), one of the only nonsedating systemic agents proven effective for neuropathic pain, is currently being evaluated in fibromyalgia. Thus, we will conduct a clinical trial to compare a PGB+ALA combination to each monotherapy for fibromyalgia. METHODS: Using a double-blind, double-dummy, crossover design, 54 adults with fibromyalgia will be randomly allocated to 1 of 6 sequences of treatment with PGB, ALA, and PGB+ALA combination. During each of 3 different treatment periods, participants will take 2 sets of capsules containing (1) ALA (or placebo) and (2) PGB (or placebo) for 31 days, followed by an 11-day taper/washout period. The primary outcome will be mean daily pain intensity (0 to 10 scale) at maximal tolerated doses (MTDs) during each period. Secondary outcomes, assessed at MTD, will include global improvement, adverse events, mood, and quality of life. RESULTS: This trial attained ethics approval March 6, 2017 (Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-313-17), and recruitment is set to start in August 2017. CONCLUSIONS: This trial will provide rigorous evidence comparing the efficacy of a PGB-ALA combination to PGB alone and ALA alone in the treatment of fibromyalgia. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number ISRCTN14939460; https://www.isrctn.com/ ISRCTN1493946 (Archived by WebCite at http://www.webcitation.org/6sFqAjxkt). CI - (c)Ian Gilron, Dongsheng Tu, Ronald Holden, Tanveer Towheed, Elizabeth Vandenkerkhof, Roumen Milev. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 04.08.2017. FAU - Gilron, Ian AU - Gilron I AUID- ORCID: 0000-0002-5293-8792 AD - Queen's University, Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada. FAU - Tu, Dongsheng AU - Tu D AUID- ORCID: 0000-0003-4842-2184 AD - Queen's University, Kingston, ON, Canada. FAU - Holden, Ronald AU - Holden R AUID- ORCID: 0000-0002-9070-2510 AD - Queen's University, Kingston, ON, Canada. FAU - Towheed, Tanveer AU - Towheed T AUID- ORCID: 0000-0001-8738-9394 AD - Queen's University, Kingston, ON, Canada. FAU - Vandenkerkhof, Elizabeth AU - Vandenkerkhof E AUID- ORCID: 0000-0003-4287-346X AD - Queen's University, Kingston, ON, Canada. FAU - Milev, Roumen AU - Milev R AUID- ORCID: 0000-0001-6884-171X AD - Queen's University, Kingston, ON, Canada. LA - eng PT - Journal Article DEP - 20170804 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 PMC - PMC5705061 OTO - NOTNLM OT - alpha-lipoic acid OT - anticonvulsant OT - antioxidant OT - fibromyalgia OT - pregabalin COIS- Conflicts of Interest: IG has received support from Biogen, Adynxx, TARIS Biomedical, AstraZeneca, Pfizer, and Johnson and Johnson and has received grants from the Canadian Institutes of Health Research, Physicians' Services Incorporated Foundation, and Queen's University. RRH has received research funding from the Canadian Institutes of Health Research, the Social Sciences and Humanities Research Council of Canada, the American Foundation for Suicide Prevention, and Queen's University. The remaining authors have no conflicts of interest to declare. EDAT- 2017/08/06 06:00 MHDA- 2017/08/06 06:01 PMCR- 2017/08/04 CRDT- 2017/08/06 06:00 PHST- 2017/05/08 00:00 [received] PHST- 2017/07/21 00:00 [accepted] PHST- 2017/07/19 00:00 [revised] PHST- 2017/08/06 06:00 [entrez] PHST- 2017/08/06 06:00 [pubmed] PHST- 2017/08/06 06:01 [medline] PHST- 2017/08/04 00:00 [pmc-release] AID - v6i8e154 [pii] AID - 10.2196/resprot.8001 [doi] PST - epublish SO - JMIR Res Protoc. 2017 Aug 4;6(8):e154. doi: 10.2196/resprot.8001.