Esketamine, Fibromyalgia, Pregabalin
Conditions
Brief summary
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
DRUGPregabalin 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.
DRUGEsketamine 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 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.
Sponsors
Beijing Tiantan Hospital
Beijing Ditan Hospital
Beijing Sanbo Brain Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the mean pain intensity | At the week 1. | This outcome is calculated as the average of daily 24-hour pain intensity scores recorded in patient diaries over 7 consecutive days using NRS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average pain intensity | At the weeks 1, 2, 4, 8, and 12 | The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable. |
| Worst pain intensity | at weeks 1, 2, 4, 8, and 12 | The worst pain intensity over the past 24 hours, rated each morning upon awakening and averaged over 7 days. The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable. |
| Proportion of patients achieving pain reduction at 50% and 30%; | at weeks 1, 2, 4, 8, and 12 | The proportion of patients achieving a ≥ 50% and ≥ 30% reduction in mean baseline pain intensity. The pain intensity will be measured based on NRS, where 0 represents no pain and 10 represents worst pain imaginable. |
| The median pain relief time | Through study completion, an average of 12 weeks | The median pain relief time, defined as the time of 50% decrease in NRS score from baseline. Pain intensity will be measured using the NRS, where 0 indicates no pain, and 10 represents the worst imaginable pain. |
| The maximal tolerated doses of pregabalin and venlafaxine | at weeks 1, 2, 4, 8, and 12 | — |
| The Revised FM Impact Questionnaire (FIQR) | At the weeks 4, 8, and 12 | The FIQR is used to assessed health status and functional disablity. FIQR is a 21-item self-administered questionnaire, based on symptoms reported within the preceding 7 days. FIQR total score ranges from 0 to 100, with higher values indicating worse health status. |
| Hospital Anxiety and Depression scale (HADS) | At the weeks 4, 8, and 12 | The HADS is used to assess anxiety (7 items) and depression (7 items). Scores range from 0 to 21 on each subscale, with higher scores indicating worse symptomatology. |
| The short-form 36 Health Survey (SF-36) | At the weeks 4, 8, and 12 | The SF-36 assesses health-related quality of life, capturing preferences across various health states. It assesses 8 dimensions: physical functioning, physical role limitations due to physical health, bodily pain, general health, vitality, social functioning, emotional role limitations due to emotional problems, and mental health. Scores range from 0 to 100 for each dimension, with higher scores indicating better health status. |
| Multidimensional Fatigue Inventory (MFI) | At the weeks 4, 8, and 12 | Fatigue is evaluated using the MFI, a 20-item assessment tool with five domains. Higher scores indicate a higher degree of fatigue. |
| Medical Outcomes Study Sleep Scale (MOS) | At the weeks 4, 8, and 12 | The MOS is a questionnaire comprising 12 items that assess various aspects of sleep using a 6-point ordinal scale (1 indicating permanence and 6 indicating absence). |
| Plasma concentrations of esketamine and its metabolites at the end of infusion | At the end of esketamine infusion, that is at day 0 | — |
| Adverse events | Through study completion, an average of 12 weeks | — |
Countries
China
Contacts
CONTACTFang Luo
Outcome results
None listed