Cargando…
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
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627027/ https://www.ncbi.nlm.nih.gov/pubmed/34838114 http://dx.doi.org/10.1186/s13063-021-05814-4 |
_version_ | 1784606774014246912 |
---|---|
author | Javorcikova, Zuzana Dangoisse, Michel Nikis, Stéphane Lechat, Jean-Paul Gillain, Aline Fils, Jean-François Van der Linden, Philippe |
author_facet | Javorcikova, Zuzana Dangoisse, Michel Nikis, Stéphane Lechat, Jean-Paul Gillain, Aline Fils, Jean-François Van der Linden, Philippe |
author_sort | Javorcikova, Zuzana |
collection | PubMed |
description | 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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05814-4. |
format | Online Article Text |
id | pubmed-8627027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86270272021-11-30 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 Javorcikova, Zuzana Dangoisse, Michel Nikis, Stéphane Lechat, Jean-Paul Gillain, Aline Fils, Jean-François Van der Linden, Philippe Trials Study Protocol 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 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05814-4. BioMed Central 2021-11-27 /pmc/articles/PMC8627027/ /pubmed/34838114 http://dx.doi.org/10.1186/s13063-021-05814-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Study Protocol Javorcikova, Zuzana Dangoisse, Michel Nikis, Stéphane Lechat, Jean-Paul Gillain, Aline Fils, Jean-François Van der Linden, Philippe 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | place of s-ketamine in fibromyalgia treatment (eskefib): study protocol for a prospective, single-center, double-blind, randomized, parallel-group, dose-escalation controlled trial |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627027/ https://www.ncbi.nlm.nih.gov/pubmed/34838114 http://dx.doi.org/10.1186/s13063-021-05814-4 |
work_keys_str_mv | AT javorcikovazuzana theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT dangoissemichel theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT nikisstephane theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT lechatjeanpaul theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT gillainaline theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT filsjeanfrancois theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT vanderlindenphilippe theplaceofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT javorcikovazuzana placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT dangoissemichel placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT nikisstephane placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT lechatjeanpaul placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT gillainaline placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT filsjeanfrancois placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial AT vanderlindenphilippe placeofsketamineinfibromyalgiatreatmenteskefibstudyprotocolforaprospectivesinglecenterdoubleblindrandomizedparallelgroupdoseescalationcontrolledtrial |