Comparison of Ketamine and Esketamine in Patients Suffering From Fibromyalgia Syndrome.

Study Overview
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Brief Summary
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Ketamine and Esketamine intravenous perfusions can modulate chronic pain. The purpose of this study is to determine if Ketamine or Esketamine are favorable for outpatients suffering from fibromyalgia.

Detailed Description
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Ketamine and Esketamine intravenous perfusions in Pain Clinic can modulate chronic pain and are therefore part of the therapeutic arsenal of the Anesthesiologist in pain management. Patients with fibromyalgia syndrome have elevated levels of glutamate in the brain. This is demonstrated by functional brain imaging techniques. Elevation of glutamate is demonstrated in the posterior insular cortex, positively correlating with lower pain thresholds which is a hallmark of fibromyalgia syndrome. Ketamine has (e.a.) an inhibitory role of the N-methyl-D-aspartate (NMDA) receptor: it is a non-competitive antagonist of the NMDA receptor. In this context, Esketamine is available recently. This is the levorotatory form of Ketamine. The main objective of this study is to measure if there is a difference between Ketamine and Esketamine on patients with fibromyalgia syndrome via the fibromyalgia impact questionnaire (FIQ) and measurement of side effects after intravenous perfusion. The fibromyalgia impact questionnaire is a global assessment of symptoms: pain, function, fatigue, stiffness, discomfort when walking up stairs, difficulties at work, anxiety, depression, days not worked and days of good quality in the past week.

Official Title
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Comparison of Ketamine and Esketamine in Ambulatory Patients Treated for Fibromyalgia Syndrome in Pain Clinic. A Single-center, Prospective, Randomized, Double-blind, Crossover Study.

Conditions
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Fibromyalgia

Intervention / Treatment
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* Drug: Ketamine 50 MG/ML
* Drug: Esketamine 25 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female Between 18 and 75 years old Reads and writes French Diagnosis of fibromyalgia syndrome according to Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) score ≥ 13/31 Both molecules (Ketamine and Esketamine) were administered at least once during an analgesic infusion session in Pain Clinic Patient with regular medical follow-up by a pain specialist at least 3 times a year Exclusion Criteria: Allergy or intolerance to Ketamine or Esketamine Current infection, fever Pregnant or breastfeeding woman Serious cardiovascular disorders and severe hypertension Increased pressure of cerebrospinal fluid and severe intracranial disease Acute intermittent porphyria Untreated epilepsy Untreated glaucoma Difficult or impossible intravenous access Chronic Liver Disease Child-Pugh C

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AB group<br>If A = Ketamine and B = Esketamine, each patient included in the study will be randomized in a sequence of administration of the two products. The AB sequence consists of patients starting with intravenous Ketamine 0,3 mg/kg in 1 hour (2 infusions separated by 6 weeks; Period 1) and continuing with intravenous Esketamine 0,15 mg/kg in 1 hour (2 infusions separated by 6 weeks; Period 2). Each patient will be monitored during the IV perfusion, and then, the next hour. The patient will receive a total of two infusions of Ketamine and two infusions of Esketamine. Each patient will be his own witness because having received the two products without knowing which he started with. A wash-out period of one week will be observed between the two administration periods to avoid so-called carry-over effects according to which the administration of the first drug could influence the effect of the second drug administered. | Drug: Ketamine 50 MG/ML<br>* Intravenous Ketalar® 0,30 mg/kg in 1 hour.<br>Drug: Esketamine 25 MG/ML<br>* Intravenous Vesierra® 0,15mg/kg in 1 hour.<br>|
| Other: BA group<br>If A = Ketamine and B = Esketamine, each patient included in the study will be randomized in a sequence of administration of the two products. The BA sequence consists of patients starting with intravenous Esketamine 0,15 mg/kg in 1 hour (2 infusions separated by 6 weeks; Period 1) and continuing with intravenous Ketamine 0,3 mg/kg in 1 hour (2 infusions separated by 6 weeks; Period 2). Each patient will be monitored during the IV perfusion, and then, the next hour. The patient will receive a total of two infusions of Esketamine and then two infusions of Ketamine. Each patient will be his own witness because having received the two products without knowing which he started with. A wash-out period of one week will be observed between the two administration periods to avoid so-called carry-over effects according to which the administration of the first drug could influence the effect of the second drug administered. | Drug: Ketamine 50 MG/ML<br>* Intravenous Ketalar® 0,30 mg/kg in 1 hour.<br>Drug: Esketamine 25 MG/ML<br>* Intravenous Vesierra® 0,15mg/kg in 1 hour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score variations of Fibromyalgia Impact Questionnaire | Fibromyalgia Impact Questionnaire (FIQ) completed by the patient. The FIQ was developed from information gathered from patient reports, functional status instruments, and clinical observations. This instrument measures physical functioning, work status (missed days of work and job difficulty), depression, anxiety, morning tiredness, pain, stiffness, fatigue, and well-being over the past week. The score is between 0 and 100. In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. | At day 0 before starting each intravenous perfusion. | 
| Score variations of Fibromyalgia Impact Questionnaire | Fibromyalgia Impact Questionnaire (FIQ) completed by the patient. The FIQ was developed from information gathered from patient reports, functional status instruments, and clinical observations. This instrument measures physical functioning, work status (missed days of work and job difficulty), depression, anxiety, morning tiredness, pain, stiffness, fatigue, and well-being over the past week. The score is between 0 and 100. In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. | At day 7 after each intravenous perfusion. | 
| Score variations of Fibromyalgia Impact Questionnaire | Fibromyalgia Impact Questionnaire (FIQ) completed by the patient. The FIQ was developed from information gathered from patient reports, functional status instruments, and clinical observations. This instrument measures physical functioning, work status (missed days of work and job difficulty), depression, anxiety, morning tiredness, pain, stiffness, fatigue, and well-being over the past week. The score is between 0 and 100. In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. | At day 14 after each intravenous perfusion. | 
| Score variations of Fibromyalgia Impact Questionnaire | Fibromyalgia Impact Questionnaire (FIQ) completed by the patient. The FIQ was developed from information gathered from patient reports, functional status instruments, and clinical observations. This instrument measures physical functioning, work status (missed days of work and job difficulty), depression, anxiety, morning tiredness, pain, stiffness, fatigue, and well-being over the past week. The score is between 0 and 100. In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. | At day 21 after each intravenous perfusion. | 
| Score variations of Fibromyalgia Impact Questionnaire | Fibromyalgia Impact Questionnaire (FIQ) completed by the patient. The FIQ was developed from information gathered from patient reports, functional status instruments, and clinical observations. This instrument measures physical functioning, work status (missed days of work and job difficulty), depression, anxiety, morning tiredness, pain, stiffness, fatigue, and well-being over the past week. The score is between 0 and 100. In the severity analysis a FIQ total score from 0 to < 39 was found to represent a mild effect, ≥ 39 to < 59 a moderate effect, and ≥ 59 to 100 a severe effect. | At day 28 after each intravenous perfusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate disturbances after intravenous perfusion of Ketamine or Esketamine | Measurement of heart rate in Pain clinic during intravenous perfusion. Measurement in beat per minute. | At the beginning (minute zero) of each intravenous perfusion. | 
| Heart rate disturbances after intravenous perfusion of Ketamine or Esketamine | Measurement of heart rate in Pain clinic during intravenous perfusion. Measurement in beat per minute. | After 30 minutes of each intravenous perfusion. | 
| Heart rate disturbances after intravenous perfusion of Ketamine or Esketamine | Measurement of heart rate in Pain clinic during intravenous perfusion. Measurement in beat per minute. | After 60 minutes of each intravenous perfusion. | 
| Heart rate disturbances after intravenous perfusion of Ketamine or Esketamine | Measurement of heart rate in Pain clinic during intravenous perfusion. Measurement in beat per minute. | After 90 minutes of each intravenous perfusion. | 
| Heart rate disturbances after intravenous perfusion of Ketamine or Esketamine | Measurement of heart rate in Pain clinic during intravenous perfusion. Measurement in beat per minute. | After 120 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for pain. | Measurement of Visual Analogue Scale (VAS) for pain. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. | At the beginning (minute zero) of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for pain. | Measurement of Visual Analogue Scale (VAS) for pain. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. | After 30 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for pain. | Measurement of Visual Analogue Scale (VAS) for pain. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. | After 60 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for pain. | Measurement of Visual Analogue Scale (VAS) for pain. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. | After 90 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for pain. | Measurement of Visual Analogue Scale (VAS) for pain. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. | After 120 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for nausea. | Measurement of Visual Analogue Scale (VAS) for nausea. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no nausea anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater nausea. | At the beginning (minute zero) of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for nausea. | Measurement of Visual Analogue Scale (VAS) for nausea. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no nausea anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater nausea. | After 30 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for nausea. | Measurement of Visual Analogue Scale (VAS) for nausea. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no nausea anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater nausea. | After 60 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for nausea. | Measurement of Visual Analogue Scale (VAS) for nausea. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no nausea anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater nausea. | After 90 minutes of each intravenous perfusion. | 
| Variations of Visual Analogue Scale for nausea. | Measurement of Visual Analogue Scale (VAS) for nausea. Using a ruler, the score is determined by measuring the distance (mm) on the 10-cm line between the no nausea anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater nausea. | After 120 minutes of each intravenous perfusion. | 
| Variations of non-invasive blood pressure. | Measurement of variations of systolic and diastolic non-invasive blood pressure with upper arm cuff. Measurement in mmHg. | At the beginning (minute zero) of each intravenous perfusion. | 
| Variations of non-invasive blood pressure. | Measurement of variations of systolic and diastolic non-invasive blood pressure with upper arm cuff. Measurement in mmHg. | After 30 minutes of each intravenous perfusion. | 
| Variations of non-invasive blood pressure. | Measurement of variations of systolic and diastolic non-invasive blood pressure with upper arm cuff. Measurement in mmHg. | After 60 minutes of each intravenous perfusion. | 
| Variations of non-invasive blood pressure. | Measurement of variations of systolic and diastolic non-invasive blood pressure with upper arm cuff. Measurement in mmHg. | After 90 minutes of each intravenous perfusion. | 
| Variations of non-invasive blood pressure. | Measurement of variations of systolic and diastolic non-invasive blood pressure with upper arm cuff. Measurement in mmHg. | After 120 minutes of each intravenous perfusion. | 
| Variations of pulse Oxygen saturation. | Measurement of variations of pulse Oxygen saturation (SpO2). Pulse oximetry is a non-invasive measures of oxygen saturation level in %. A normal SpO2 is typically between 95 and 100 percent. A SpO2 < 95 percent is considered low. | At the beginning (minute zero) of each intravenous perfusion. | 
| Variations of pulse Oxygen saturation. | Measurement of variations of pulse Oxygen saturation (SpO2). Pulse oximetry is a non-invasive measures of oxygen saturation level in %. A normal SpO2 is typically between 95 and 100 percent. A SpO2 < 95 percent is considered low. | After 30 minutes of each intravenous perfusion. | 
| Variations of pulse Oxygen saturation. | Measurement of variations of pulse Oxygen saturation (SpO2). Pulse oximetry is a non-invasive measures of oxygen saturation level in %. A normal SpO2 is typically between 95 and 100 percent. A SpO2 < 95 percent is considered low. | After 60 minutes of each intravenous perfusion. | 
| Variations of pulse Oxygen saturation. | Measurement of variations of pulse Oxygen saturation (SpO2). Pulse oximetry is a non-invasive measures of oxygen saturation level in %. A normal SpO2 is typically between 95 and 100 percent. A SpO2 < 95 percent is considered low. | After 90 minutes of each intravenous perfusion. | 
| Variations of pulse Oxygen saturation. | Measurement of variations of pulse Oxygen saturation (SpO2). Pulse oximetry is a non-invasive measures of oxygen saturation level in %. A normal SpO2 is typically between 95 and 100 percent. A SpO2 < 95 percent is considered low. | After 120 minutes of each intravenous perfusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibromyalgia, Ketamine, Esketamine, Fibromyalgia Impact Questionnaire, Side effects, Chronic pain