Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 8;6(6):e111.
doi: 10.2196/resprot.7493.

Pain Improvement With Novel Combination Analgesic Regimens (PAIN-CARE): Randomized Controlled Trial Protocol

Ian Gilron  1 , Dongsheng Tu  2 , Ronald Holden  2 , Alan C Jackson  3 , Nader Ghasemlou  2 , Scott Duggan  2 , Elizabeth Vandenkerkhof  2 , Roumen Milev  2
Affiliations

Pain Improvement With Novel Combination Analgesic Regimens (PAIN-CARE): Randomized Controlled Trial Protocol

Ian Gilron et al. JMIR Res Protoc. .

Abstract

Background: Neuropathic pain (NP) (including painful diabetic neuropathy, postherpetic neuralgia, etc) affects approximately 7% to 8% of the population and is associated with a devastating symptom burden as well as a profound economic impact for patients, their families, and the health care system. Current therapies have limited efficacy and dose-limiting adverse effects (AEs). Rational combination therapy with carefully selected NP drugs has shown potential for measurable improvements in pain relief, quality of life, and health care use. Today, over half of NP patients concurrently receive 2 or more analgesics but combination use is based on little evidence. Research is urgently needed to identify safer, more effective combinations.

Objective: We hypothesize that analgesic combinations containing at least 1 nonsedating agent would be as safe but more effective than either monotherapy without increasing overall AEs because of additive pain relief. Pregabalin (PGB), a sedating anticonvulsant, is proven effective for NP; the antioxidant alpha-lipoic acid (ALA) is one of the only nonsedating systemic agents proven effective for NP. Thus, we will conduct a clinical trial to compare a PGB+ALA combination to each monotherapy for NP.

Methods: Using a double-blind, double-dummy, crossover design, 54 adults with NP 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 (0-10) at maximally tolerated dose (MTD) during each period. Secondary outcomes, assessed at MTD, will include global improvement, adverse events, mood, and quality of life.

Results: Participant recruitment is expected to begin September 1, 2017. The proposed trial was awarded external peer-reviewed funding by the Canadian Institutes of Health Research (Canada) on July 15, 2016.

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 NP.

Trial registration: International Standard Randomized Controlled Trial Number ISRCTN14577546; http://www.isrctn.com/ISRCTN14577546?q=&filters=conditionCategory:Signs%20and%20Symptoms,trialStatus: Ongoing,recruitmentCountry:Canada&sort=&offset=1&totalResults=2&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation.org/6qvHFDc6m).

Keywords: alpha-lipoic acid; anticonvulsant; antioxidant; neuropathic pain; pregabalin.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: IG has received support from 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. ACJ has received grants from the Canadian Institutes of Health Research, Research Manitoba (formerly the Manitoba Health Research Council), and the University of Manitoba. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Trial design.
Figure 2
Figure 2
Trial design, continued.
Figure 3
Figure 3
Study drug schedules.
Figure 4
Figure 4
Schedule of assessments.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Reitsma ML, Tranmer JE, Buchanan DM, Vandenkerkhof EG. The prevalence of chronic pain and pain-related interference in the Canadian population from 1994 to 2008. Chronic Dis Inj Can. 2011 Sep;31(4):157–164. http://www.phac-aspc.gc.ca/publicat/cdic-mcbc/31-3/ar-04-eng.php - PubMed
    1. St Sauver JL, Warner DO, Yawn BP, Jacobson DJ, McGree ME, Pankratz JJ, Melton LJ, Roger VL, Ebbert JO, Rocca WA. Why patients visit their doctors: assessing the most prevalent conditions in a defined American population. Mayo Clin Proc. 2013 Jan;88(1):56–67. doi: 10.1016/j.mayocp.2012.08.020. http://europepmc.org/abstract/MED/23274019 - DOI - PMC - PubMed
    1. Institute of Medicine . Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press; 2011. - PubMed
    1. VanDenKerkhof EG, Mann EG, Torrance N, Smith BH, Johnson A, Gilron I. An epidemiological study of neuropathic pain symptoms in Canadian adults. Pain Res Manag. 2016;2016:9815750. doi: 10.1155/2016/9815750. http://europepmc.org/abstract/MED/27445636 - DOI - PMC - PubMed
    1. Gilron I, Baron R, Jensen TS. Neuropathic pain: principles of diagnosis and treatment. Mayo Clin Proc. 2015 Apr;90(4):532–545. doi: 10.1016/j.mayocp.2015.01.018. - DOI - PubMed

LinkOut - more resources