ESKETamine for FIBromyalgia Treatment (ESKEFIB)

Intravenous Infusions of S-KETAMINE in Fibromyalgia Syndromes: an Exploratory Study.

Fibromyalgia is a cause of chronic pain, classified by the Internal Classification of Diseases (ICD) as a primary chronic pain with specific diagnostic criteria established by the American College of Rheumatology (ACR). No treatment to its complete cure is available at this time, all treatments having as purpose pain relief and an improvement of quality of life by combining pharmacologic and nonpharmacologic treatments. One of the mechanisms proposed in fibromyalgia is the central sensitisation phenomenon, by which the central nervous system becomes "hypersensitive" to nociceptive or non-nociceptive stimuli. The receptor involved in this phenomenon is the N-methyl-D-aspartate receptor to which ketamine binds. Ketamine has therefore been proposed as a co-treatment in chronic pain with central sensitization phenomena, such as fibromyalgia.

Study Overview

• Status: Recruiting
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: Active comparator; Drug: S-Ketamine Low dose; Drug: S-Ketamine High dose

Detailed Description

Ketamine is a drug used for anesthesia since the 1970s, acting as an antagonist to the N-methyl-D-aspartate receptor located in the central nervous system. It has two stereoisomers : R +ketamine and S - ketamine, the latter being about two to four times more potent. S-ketamine also has the advantages of producing less psychotropic effects, less tiredness and a lower temporary cognitive impairment than the racemic mixture at equianalgesic doses. Being first used as an anesthetic, in the last twenty years, ketamine's indications expanded to other domains, such as treatment of depression or off label use for chronic pain relief. Chronic pain is a multidimensional syndrome that touches 17-44% of the population of western countries. Fibromyalgia is a cause of chronic pain, classified by the Internal Classification of Diseases (ICD) as a primary chronic pain with specific diagnostic criteria established by the American College of Rheumatology (ACR). No treatment to its complete cure is available at this time, all treatments having as purpose pain relief and an improvement of quality of life by combining pharmacologic and nonpharmacologic treatments (as given by the European League Against Rheumatism (EULAR) guidelines). One of the mechanisms proposed in fibromyalgia is the central sensitisation phenomenon, by which the central nervous system becomes "hypersensitive" to nociceptive or non-nociceptive stimuli. The receptor involved in this phenomenon is the N-methyl-D-aspartate receptor to which ketamine binds. Ketamine has therefore been proposed as a co-treatment in chronic pain with central sensitization phenomena, such as fibromyalgia.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Paul Lechat, MD; Phone Number: 4071 00 32 71 10; Email: jean-paul.lechat@ghdc.be
• Study Contact Backup: Name: Zuzana Javorcikova, MD; Phone Number: 1109 00 32 474 64; Email: z.javorcikova.pro@gmail.com

Study Locations

• Belgium
  • Hainaut
    • Gilly, Hainaut, Belgium, 6060
      • Recruiting
      • Grand Hôpital de Charleroi
      • Contact: Zuzana Javorcikova, MD; Phone Number: 1109 00 32 474 64; Email: z.javorcikova.pro@gmail.com
      • Contact: Jean-Paul Lechat, MD; Phone Number: 4071 00 32 71 10; Email: jean-paul@ghdc.be
      • Sub-Investigator: Philippe Van der Linden, MD, PhD
      • Sub-Investigator: Michel Dangoisse, MD
      • Sub-Investigator: Stéphane Nikis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients suffering from chronic pain (as defined by International Association for the Study of Pain) being diagnosed as fibromyalgia according to the American College of Rheumatology 2016 criteria
• patients qualified for the treatment by S-ketamine as established by our latest clinical practice
• patients aged 18-65 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo; Clonidine at a dose of 1 microg/kg Magnesium sulfate at a dose of 40 mg/kg	Drug: Active comparator; The active comparator is composed of clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride
Experimental: S-Ketamine Low dose; S-Ketamine at a dose of 0.2 mg/kg	Drug: Active comparator; The active comparator is composed of clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride; Drug: S-Ketamine Low dose; The arm 1 is composed of esketamine 0.2 mg/kg and clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride.
Experimental: S-ketamine High dose; S-ketamine at a dose of 0.4 mg/kg	Drug: Active comparator; The active comparator is composed of clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride; Drug: S-Ketamine High dose; The arm 2 is composed of esketamine 0.4 mg/kg and clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is twofold, aiming on one side pain relief and on the other the improvement of the patient's functional status	Pain relief will be considered as a two point decrease on the Brief Pain Inventory (BPI) pain severity index at twelve weeks follow-up. (Two points being established as the Minimal Clinically Important Difference (MCID) for fibromyalgic patients). The functional status will be evaluated by the BPI Interference scale. An improvement will be considered as a one point reduction on this index (as established by the MCID). The primary outcome is to determine whether the association of S-ketamine to the analgesic treatment will increase the number of patients showing a clinically significant improvement of pain and/or functional status.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients showing 50 % reduction in the BPI (Brief Pain Inventory) pain index	Measures will be done with different questionnaires	12 weeks

Collaborators and Investigators

• Sponsor: Grand Hôpital de Charleroi
• Investigators: Principal Investigator: Jean-Paul Lechat, MD, Grand Hôpital de Charleroi

Publications and helpful links

General Publications

• Javorcikova Z, Dangoisse M, Nikis S, Lechat JP, Gillain A, Fils JF, Van der Linden P. 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. Trials. 2021 Nov 27;22(1):853. doi: 10.1186/s13063-021-05814-4.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: June 15, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 18, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: ESKEFIB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No