Ketamine's Efficiency in the Treatment of Chronic Pain: Kynurenin Pathway
- Conditions
- NeuralgiaChronic PainInflammation
- Interventions
- Registration Number
- NCT03513822
- Lead Sponsor
- Redar
- Brief Summary
The kynurenine pathway is involved in hyperalgesia. This pathway is activated by inflammation. Ketamine would interact with the kynurenine pathway and inflammation. Our working hypotheses are: the clinical effects of ketamine on neuropathic pain are greater in the presence of systemic inflammation and the mechanism of action involves an interaction on the kynurenine pathway.
Study design: Interventional randomized placebo-controlled clinical trial.
Main goals:
1. To show a better clinical efficacy of ketamine in chronic pain in patients with an inflammatory component.
2. Explore the anti-inflammatory activity of ketamine through the Kynurenine pathway.
- Detailed Description
The kynurenine pathway is involved in hyperalgesia. This pathway is activated by inflammation. Ketamine would interact with the kynurenine pathway and inflammation. Our working hypotheses are: the clinical effects of ketamine on neuropathic pain are greater in the presence of systemic inflammation and the mechanism of action involves an interaction on the kynurenine pathway.
Study design: Interventional randomized placebo-controlled clinical trial.
Main goals:
1. To show a better clinical efficacy of ketamine in chronic pain in patients with an inflammatory component.
2. Explore the anti-inflammatory activity of ketamine through the Kynurenine pathway.
Population Adult, medullary injured (BM), with chronic neuropathic pain (DN). 4 groups: BM with DN with bedsore Ketamine Group versus Placebo Group BM with DN without bedsore group Ketamine versus Placebo Group
Intervention Ketamine infusion 1 mg / kg IVSE over two hours versus Nacl perfusion 0.9%
 Primary judgment criterion Decrease by more than 30% the intensity of neuropathic pain evaluated at the moment on a numerical scale of 10 points between H0 and H4. Comparison of groups two by two.
Secondary judgment criterions:
NPSI score (Neuropathic pain symptom inventory) at H1, H4, D1, D4, J7 Sub score of NPSI; H1, H4, J1, J4, J7 Depression Scale HADS (Hospital Anxiety Depression Scale) J0, J1, J7 Plasma serotonin (5-HT) kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (KYN / TRP ratio), kynurenic acid ( KA) and quinolinic acid (QA), as well as 3 proinflammatory cytokines IL-1β, IL-6, and TNF-α before perfusion and H4 perfusion.
In parallel blood samples will be collected to study the activation of the kynurenine pathway in response to inflammation due to a pressure ulcer.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 48
- Adults speaking and understanding French
- presenting chronic neuropathic pain as defined by IASP
- Painful intensity> or = to 6/10 during the week preceding the inclusion - Medullary lesion, whatever the origin (traumatic, degenerative, tumoral, postoperative), responsible for paraplegia in a chronic state.
- Able to give informed consent, after clear, fair and appropriate information
- Having given their consent by a written consent signature.
- Hypersensitivity to ketamine or any of its components
- Participation in another interventional trial, or participation in another trial.
- Patient unable to give consent.
- Pregnancy or breastfeeding
- Refusal to sign the consent
- Cardiovascular diseases associated in particular with disorders of rhythm and severe cardiac insufficiency, coronary insufficiency, discovered on examination, on ECG or by biological balance or known. - unstabilized HTA> 180/100 mmHg
- Severe hepatic and / or renal hepatic insufficiency.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chronic neuropathic pain without bedsore Placebo group Placebos Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and no ulcer pressure (no inflammation factor). Midazolam 1mg before infusion. Sodium chloride infusion IVSE during 2 hours. Rate of administration : Speed = patient weight divided by four. One and only perfusion. Chronic neuropathic pain and bedsore Ketamine group Ketamine 10 MG/ML Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and ulcer pressure (inflammation factor). Midazolam 1mg before infusion. KETAMINE INFUSION IVSE 1mg/kg during 2 hours (0,5mg/kg/h). Preparation of 100mg in fifty cc, syringe with 2mg/ml. Rate of administration: Speed = Patient weight divided by four. Maximum 100mg. One and only perfusion. Chronic neuropathic pain and bedsore Placebo group Placebos Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and ulcer pressure (inflammation factor). Midazolam 1mg before infusion. Sodium chloride infusion IVSE during 2 hours. Rate of administration : Speed = patient weight divided by four. One and only perfusion. Chronic neuropathic pain and bedsore Ketamine group Midazolam 1 MG/ML Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and ulcer pressure (inflammation factor). Midazolam 1mg before infusion. KETAMINE INFUSION IVSE 1mg/kg during 2 hours (0,5mg/kg/h). Preparation of 100mg in fifty cc, syringe with 2mg/ml. Rate of administration: Speed = Patient weight divided by four. Maximum 100mg. One and only perfusion. Chronic neuropathic pain and bedsore Placebo group Midazolam 1 MG/ML Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and ulcer pressure (inflammation factor). Midazolam 1mg before infusion. Sodium chloride infusion IVSE during 2 hours. Rate of administration : Speed = patient weight divided by four. One and only perfusion. Chronic neuropathic pain without bedsore Ketamine group Midazolam 1 MG/ML Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and no ulcer pressure (no inflammation factor). Midazolam 1mg before infusion. KETAMINE INFUSION IVSE 1mg/kg during 2 hours (0,5mg/kg/h). Preparation of 100mg in fifty cc, syringe with 2mg/ml. Rate of administration: Speed = Patient weight divided by four. Maximum 100mg. One and only perfusion. Chronic neuropathic pain without bedsore Placebo group Midazolam 1 MG/ML Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and no ulcer pressure (no inflammation factor). Midazolam 1mg before infusion. Sodium chloride infusion IVSE during 2 hours. Rate of administration : Speed = patient weight divided by four. One and only perfusion. Chronic neuropathic pain without bedsore Ketamine group Ketamine 10 MG/ML Spinal cord injury population with central neuropathic pain at the lesional or sub-lesion level, chronically (for more than three months). Patients medullary wounded with chronic pain and no ulcer pressure (no inflammation factor). Midazolam 1mg before infusion. KETAMINE INFUSION IVSE 1mg/kg during 2 hours (0,5mg/kg/h). Preparation of 100mg in fifty cc, syringe with 2mg/ml. Rate of administration: Speed = Patient weight divided by four. Maximum 100mg. One and only perfusion.
- Primary Outcome Measures
Name Time Method Numeric pain rating scale decrease between H0 and H4. 4 hours after the end of infusion Numeric pain rating scale is a scale from 0 to 10. 0 is no pain, 10 is the worst pain we could imagine. The first outcome is decreasing the intensity of neuropathic pain evaluated at the moment on a numerical scale of 10 points at H4. Comparison of groups two by two.
- Secondary Outcome Measures
Name Time Method Paraclinical: Kynurenine pathway levels : IL6 Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of Interleukin 6 (picograms/milliliter)
Paraclinical: Kynurenine pathway levels : SEROTONIN Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of SEROTONIN (millimoles/liter)
Paraclinical: Kynurenine pathway levels : KYNURENINE Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of KYNURENINE (millimoles/liter)
Paraclinical: Kynurenine pathway levels : IDO ACTIVITY Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of INDOLEAMINE DIOXYGENASE ACTIVITY (division Kynurenine/Tryptophane quote)
Paraclinical: Kynurenine pathway levels : KYNURENIC ACID Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of Kynurenic acid (millimoles/liter)
Paraclinical: Kynurenine pathway levels : QUINOLINIC ACID Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of Quinolinic acid (millimoles/liter)
Paraclinical: Kynurenine pathway levels : IL1 Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of Interleukin 1 (picograms/milliliter)
Paraclinical: Kynurenine pathway levels: TNF alpha Hour 0 and Hour 6 (4 hours after the ending of infusion) Levels of TNF alpha (picograms/milliliter)
Clinical: Neuropathic pain symptom inventory Hour 0, Day 1, Day 4, Day 7 NPSI scoring: Neuropathic pain symptom inventory. A composite score composed by neuropathic pain components: Burning, Pressure, Squeezing, Electric shocks, Stabbing, Evoked by brushing, evoked by pressure, evoked by cold stimuli, pins and needles, tingling. Two questions about the time of pain for twenty four hours, and the numbers of crisis. Score from 0 to 100. 100 is the maximum.
Clinical: Pain timeline Seven days Timeline of self assessment on a simple numeric scale of the pain three times a day during a week. Numeric pain rating scale is a scale from 0 to 10. 0 is no pain, 10 is the worst pain we could imagine.
Percentage overall improvement in pain over a week with self assessment Between Hour 0 and Day 7 Self assessment of the global improvement in pain over the week after infusion
Clinical: Subscore of Neuropathic pain symptom inventory Hour 0, Day 1, Day 4, Day 7 Subscore on NPSI scoring: NEUROPATHIC PAIN SYMPTOM INVENTORY, subscore are burning from 0 to 10, pressing (deep) spontaneous pain from 0 to 10, paroxysmal pain from 0 to 10, evoked pain from 0 to 10, paresthesia or dysesthesia from 0 to 10 (0 is the minimal, 10 is the maximal value for each of the component).
Clinical: Hospital anxiety and depression scale Hour 0, Day 7. Recording scoring on hospital anxiety and depression scale. HADS scale is a tool to detect anxiety and depressive disorders. It includes fourteen questions from 0 to 3 points each. Seven are related to anxiety. Seven are related to depressive mood. It permits to obtain 2 different scales with the maximum of each of 21.
Percentage overall improvement in mood over a week with self assessment Between Hour 0 and day 7 Self assessment of the global improvement of the mood over the week after infusion
Clinical: Pain area on a body cartography Hour 0, Day 1, Day 7. Evaluation of pain area on a body surface cartography
Clinical: Ketamine adverse effects Hour 0 to hour 4 Recording ketamine adverse effects during and right after the infusion
Paraclinical: Kynurenine pathway activation with ulcer pressure Hour 0 Studying the levels of the kynurenine pathway elements between patients with inflammatory component (ulcer pressure) and without inflammatory component (without ulcer pressure)
Trial Locations
- Locations (1)
Raymond Poincaré Hospital
🇫🇷Garches, Hauts De Seine, France