The Efficacy and Safety of Short Term S-ketamine Infusion as an Adjunctive Therapy in Patients With Fibromyalgia

Official title

Comparing the Efficacy and Safety of Conventional Therapy With Conventional Therapy Combined Esketamine in the Treatment of Fibromyalgia: A Multicenter Clinical Study

Overview

Fibromyalgia is a chronic pain syndrome where current medications have limited efficacy and a slow onset of action. Esketamine shows potential as a rapid-acting analgesic, but previous low-dose studies failed to demonstrate long-term benefits. The efficacy of higher-dose ESK as an adjunctive therapy when standard treatments are insufficient remains unclear.

Interventions

• Drug Pregabalin and venlafaxine concomitant therapy
  The control group will only receive an increased dosage of pregabalin and venlafaxine regimen. Each participant will be instructed with the same dose escalation regimen, until they reach the maximal tolerated dose (MTD) or the ceiling dose or the maximum daily recommended dose. The maximum recommended daily dose of pregabalin was 450 mg and venlafaxine was 225 mg.
• Drug Esketamine plus pregabalin and venlafaxine concomitant therapy
  The treatment group, in addition to the increased pregabalin and venlafaxine medication dosage regimen, will also receive a single intravenous infusion of esketamine on the day of enrollment. Plasma concentrations of esketamine and its metabolites will be measured at the end of infusion to enable a limited characterization of systemic exposure and to support exploratory exposure-response analyses. Each participant will be instructed with the same dose escalation regimen, until they reach the max

Primary outcome measures

• Change from baseline in the mean pain intensity [Time frame: At the week 1.]

Secondary outcome measures (12)

• Average pain intensity [Time frame: At the weeks 1, 2, 4, 8, and 12]
• Worst pain intensity [Time frame: at weeks 1, 2, 4, 8, and 12]
• Proportion of patients achieving pain reduction at 50% and 30%; [Time frame: at weeks 1, 2, 4, 8, and 12]
• The median pain relief time [Time frame: Through study completion, an average of 12 weeks]
• The maximal tolerated doses of pregabalin and venlafaxine [Time frame: at weeks 1, 2, 4, 8, and 12]
• The Revised FM Impact Questionnaire (FIQR) [Time frame: At the weeks 4, 8, and 12]
• Hospital Anxiety and Depression scale (HADS) [Time frame: At the weeks 4, 8, and 12]
• The short-form 36 Health Survey (SF-36) [Time frame: At the weeks 4, 8, and 12]
• Multidimensional Fatigue Inventory (MFI) [Time frame: At the weeks 4, 8, and 12]
• Medical Outcomes Study Sleep Scale (MOS) [Time frame: At the weeks 4, 8, and 12]
• Plasma concentrations of esketamine and its metabolites at the end of infusion [Time frame: At the end of esketamine infusion, that is at day 0]
• Adverse events [Time frame: Through study completion, an average of 12 weeks]

Eligibility criteria

Inclusion criteria

• Patients between ages over 18 years with proper cognitive function and language skills for the study;
• Patients diagnosed with FM as defined by the ACR FM diagnostic criteria;
• Patients who have experienced insufficient symptom relief with non-pharmacological treatments and have not previously received recommended pharmacological treatment for FM;
• A score of ≥ 4 on the average pain intensity over 7 days on the numeric rating scale (NRS) at baseline.

Exclusion criteria

• Patient refusal;
• Inability to sign informed consent;
• Had other secondary FM, this is, hypothyroidism, nutritional deficiency, diabetes mellitus, connective tissue disorder;
• Had psychiatric disorder, this is, schizophrenia and other psychotic disorder, bipolar disorder, or personality disorder;
• Obstructive sleep apnea syndrome or a STOP-Bang score ≥ 3;
• History of treatment with pregabalin and/or venlafaxine for any disease;
• History of treatment with intravenous ketamine or ESK for chronic pain;
• Presence of other painful ailments such as inflammatory rheumatic disease;
• Uncontrolled diabetes, refractory hypertension, malignancies, narrow-angle glaucoma, hyperthyroidism, severe cardiovascular disease or any other contraindications to esketamine;
• History of prescription drug abuse, alcoholism or illicit drug use;
• Pregnant or lactating women;
• Allergic to any of the study drugs.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Beijing, Beijing 100070 — Beijing

Publications

• Shrestha N, Liu M, Niu S, Cheng H, Sun Y, Mei S, Luo F. Efficacy and Safety of Adjunctive Therapy Using Single High-Dose S-Ketamine Infusion for Fibromyalgia: A Multicenter, Prospective, Randomized, Controlled, Open-Label, Blinded-Endpoint Study Protocol. J Pain Res. 2026 May 16;19:598907. doi: 10.2147/JPR.S598907. eCollection 2026. PMID 42170615

Identifiers

NCT: NCT07230171 · KY2025-217-03-06

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗