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. 2021 Nov 27;22(1):853.
doi: 10.1186/s13063-021-05814-4.

The place of S-ketamine in fibromyalgia treatment (ESKEFIB): study protocol for a prospective, single-center, double-blind, randomized, parallel-group, dose-escalation controlled trial

Zuzana Javorcikova  1 , Michel Dangoisse  2 , Stéphane Nikis  3 , Jean-Paul Lechat  2 , Aline Gillain  2 , Jean-François Fils  4 , Philippe Van der Linden  2   5
Affiliations

The place of S-ketamine in fibromyalgia treatment (ESKEFIB): study protocol for a prospective, single-center, double-blind, randomized, parallel-group, dose-escalation controlled trial

Zuzana Javorcikova et al. Trials. .

Abstract

Background: Fibromyalgia is a chronic multidimensional pain disease with no curative treatment currently available. Its management relies on a multimodal approach involving pharmacologic and non-pharmacologic elements. Because a suggested factor in its etiology is a central sensitization phenomenon involving the N-methyl-D-aspartate receptor (NMDAR), NMDAR antagonists have been proposed as a treatment target. Ketamine and its levogyre form, S-ketamine, have been used to treat chronic pain for many years without consensus about their therapeutic efficiency. We aim to assess the efficacy of S-ketamine as a co-treatment for fibromyalgia.

Methods: This prospective, randomized, single-center, double-blind, parallel-group, dose-escalation trial will compare a co-treatment with S-ketamine (intervention) to a control treatment without S-ketamine (control). It will consist of two successive cohorts with 2:1 randomization ratio (S-ketamine at two different doses: control) with 105 participants in each cohort. The protocol follow-up time will be 12 weeks, including 3 visits for the treatment (week 0, week 2, and week 4) and 3 visits for follow-up (week 6, week 9, and week 12). Our primary outcome, pain relief and/or better patient function, will be assessed with the Brief Pain Inventory questionnaire. The statistical analysis will be performed on an intention-to-treat basis. If the primary outcome is reached at the end of follow-up in the first cohort with low-dose S-ketamine (0.2 mg/kg), the trial will end. If not, the trial will continue with the second cohort and high-dose S-ketamine (0.4 mg/kg).

Discussion: The challenge of our trial is the inclusion of a large number of participants in comparison to other trials involving ketamine or S-ketamine infusions for chronic pain management. The originality of our protocol is to include functionality in addition to pain relief as a primary outcome because these two endpoints are not linked in a linear way. For some patients, functional status is more important than pain relief.

Trial registration: EudraCT reference: 2020-000473-25, ClinicalTrials.gov : NCT04436250, first posted June 18, 2020; last updated July 21, 2020. Protocol version 2.2 issued on September 30, 2020, after a revision by the ethics committee. https://clinicaltrials.gov/ct2/show/NCT04436250.

Keywords: Chronic pain; Fibromyalgia; N-Methyl-D-aspartate receptor; S-ketamine; Treatment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Trial design
Fig. 2
Fig. 2
Treatment preparation steps. ⏏, laminar flow hood; S-ket, S-ketamine; N°, recognition number; MgSO4, magnesium sulfate; Clo, clonidine; IMD, Investigational Medication Drug; NIMD, non-investigational medication drug
Fig. 3
Fig. 3
Recruitment process. CSI, Central Sensitization Inventory; EULAR, European League Against Rheumatism
See this image and copyright information in PMC

References

    1. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10(4):287–333. doi: 10.1016/j.ejpain.2005.06.009. - DOI - PubMed
    1. Langley PC. The prevalence, correlates and treatment of pain in the European Union. Curr Med Res Opin. 2011;27(2):463–480. doi: 10.1185/03007995.2010.542136. - DOI - PubMed
    1. Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Korwisi B, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. Chronic pain as a symptom or a disease: the IASP Classification of Chronic Pain for the International Classification of Diseases (ICD-11) Pain. 2019;160(1):19–27. doi: 10.1097/j.pain.0000000000001384. - DOI - PubMed
    1. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Häuser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46(3):319–329. doi: 10.1016/j.semarthrit.2016.08.012. - DOI - PubMed
    1. Hawkins RA. Fibromyalgia: a clinical update. J Am Osteopath Assoc. 2013;113(9):680–689. doi: 10.7556/jaoa.2013.034. - DOI - PubMed

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