Fibromyalgia Syndrome
Conditions
Interventions
Trade Name: Ketanest-S
Product Name: Esketamine
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous
Sponsors
Leiden University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosed with FMS by a rheumatologist - Females - Age between 18 and 75 years old - Dutch speaking participants Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - A medical diagnosis other than fibromyalgia explaining the chronic pain symptoms. - Presence of hypertension or any other severe cardiovascular co-morbidity (e.g., heart failure (NYHA III or IV), neuromuscular diseases, pulmonary obstructive & restrictive diseases, kidney failure (eGFR = 60), liver diseases or epilepsy) - Presence of any severe psychiatric disease not related to symptoms of FMS (e.g., schizophrenia, schizoaffective disorders, severe anxiety or depression (HADS > 15), bipolar disorder, dissociative personality disorder, or (previous) addiction to strong analgesics. - Presence of any allergy for S(+)-ketamine, midazolam, ondansetron or flumazenil - Long term use of medicine that is contra-indicated when administering S(+)-ketamine or midazolam: NMDA-receptor antagonists, parasympathomimetics (e.g., bronchodilators), thyroid hormones, vasopressin, CYP3A4 liver enzyme inhibitors (e.g., verapamil, diltiazem, or certain antibiotics), CYP3A4 liver enzyme inductors (e.g., rifampicin, carbamazepine, fenytoin), and strong opioids (e.g., morphine, fentanyl, heroin) - Previous experience(s) with S(+)-ketamine in a medical setting or previous experience with recreational racemic Ketamine use. - Use of painkillers different than usual dose of treatment on the day of experimentation. - Use of alcohol or drugs 24 hours prior to the hospital visits - Use of caffeine 12 hours prior to the hospital visits - Body weight > 100kg or BMI >35 - Presence of pregnancy or lactation - Presence of an ICD, pacemaker or implanted medication pump - Presence of chronic pain at the local site of experimental pain stimuli or monitoring devices. - Implanted materials in either arm (e.g., non-removable piercings)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The main goal for this study is to assess changes in pain sensitivity due to pharmacological conditioning with S(+)-ketamine compared to pharmacological conditioning with (combined) placebo medication. Pain sensitivity is quantified in this study by investigating the presence three different Quantitative Sensory Testing (QST) modalities; pain pressure thresholds (PPT’s), pressure wind-up pain and aftersensations. The QSTs in this study are executed with pressure stimuli (in kg) applied with a handheld analogue algometer capable of delivering 10kg of force (Force Dial; Wagner Instruments, Greenwhich CT, USA, see also D6.3 Manual Algometer). Pressure pain stimuli seem to be the most adequate method of QST application in patients with FMS as they correlate better to their clinical pain then for example heat pain stimuli, correlate to their CNS hyperexcitability (by means of increased glutamate levels) and respond well to ketamine treatment. The pressure stimuli are applied to the thenar muscles of the dominant hand and ipsilateral tibialis anterior muscle. These muscle areas are preferred because they can accurately display any signs of pain sensitivity, have shown acceptable reliability, are known to be sensitive to ketamine treatment, and are also accessible during testing. PPT’s are the main parameter for this study. The main endpoint is a difference between PPT levels at baseline and directly post-intervention (at T = 60mins) between the study groups. The PPT’s are examined by applying three different pressure stimuli (kg force) at three adjacent areas on the hand and lower leg. The three pressure stimuli necessary to evoke pain are then averaged out to calculate a mean pressure threshold in Kg force. The mean pressure thresholds are subsequently averaged out for body location, as a minimum role for body location is expected. PPT’s are preferred as the main parameter in this study as they: 1) Are able to reliably demonstrate pain hypersensit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The first secondary endpoint is the conditioned effects of S(+)-ketamine on wind-up pain measured as the change from baseline and compared to the conditioned effects in the placebo groups. The phenomenon of wind-up pain can be measured with temporal summation, a dynamic QST modality. Temporal summation is assessed by applying pressure pain at pain threshold level while asking participants to rate the 1st, 5th, and 10th stimulus on an NRS scale. A single temporal summation or wind-up pain score is then obtained by subtracting the 1st stimulus from the 10th (final) stimulus. The wind-up pain is assessed at two body locations: the hand and lower leg and the wind-up pain score will be averaged out for both locations as a minimal influence is expected. Reliability of pressure temporal summation was investigated in musculoskeletal trauma patients and was moderate to excellent (ICC range 0.69–0.91). Temporal summation is a valid measure for detecting signs of CS pain and is therefore used in this study. The second secondary endpoint is the conditioned effects of S(+)-ketamine on aftersensations measured as the change from baseline and compared to the conditioned effects in the placebo groups. The aftersensations are obtained by asking a participant to rate late pain (in NRS) 15 seconds after the 10th summation stimulus on the hand and lower leg and subtracting this pain score from the 10th score of the summation sequence. Similar to the wind-up pain and pressure pain thresholds, the scores for aftersensation of the hand and lower leg will be averaged out. The third secondary endpoint is going to be the influence of body location on the QST’s (temporal summation, PPT and aftersensations). Although expected to be minimal, the effects of (conditioned) S(+)-ketamine and/or midazolam on QST’s for different body locations will be controlled for. The fourth secondary endpoint is going to be the change in clinical pain intensity from baseline to dire | — |
Countries
Netherlands
Contacts
Public ContactInstitute of Psychology
Leiden University
Outcome results
None listed