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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
48
Ketamine infusion 1mg/kg with electric syringe during 2 hours.
Sodium chloride infusion with the same rate, electric syringe during 2 hours.
Bolus of Midazolam 1mg before each perfusion.
Raymond Poincaré Hospital
Garches, Hauts De Seine, France
RECRUITINGNumeric pain rating scale decrease between H0 and H4.
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.
Time frame: 4 hours after the end of infusion
Paraclinical: Kynurenine pathway levels : SEROTONIN
Levels of SEROTONIN (millimoles/liter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels : KYNURENINE
Levels of KYNURENINE (millimoles/liter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels : IDO ACTIVITY
Levels of INDOLEAMINE DIOXYGENASE ACTIVITY (division Kynurenine/Tryptophane quote)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels : KYNURENIC ACID
Levels of Kynurenic acid (millimoles/liter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels : QUINOLINIC ACID
Levels of Quinolinic acid (millimoles/liter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels : IL1
Levels of Interleukin 1 (picograms/milliliter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels : IL6
Levels of Interleukin 6 (picograms/milliliter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Paraclinical: Kynurenine pathway levels: TNF alpha
Levels of TNF alpha (picograms/milliliter)
Time frame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
Clinical: Neuropathic pain symptom inventory
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.
Time frame: Hour 0, Day 1, Day 4, Day 7
Clinical: Pain timeline
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.
Time frame: Seven days
Percentage overall improvement in pain over a week with self assessment
Self assessment of the global improvement in pain over the week after infusion
Time frame: Between Hour 0 and Day 7
Clinical: Subscore of Neuropathic pain symptom inventory
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).
Time frame: Hour 0, Day 1, Day 4, Day 7
Clinical: Hospital anxiety and depression scale
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.
Time frame: Hour 0, Day 7.
Percentage overall improvement in mood over a week with self assessment
Self assessment of the global improvement of the mood over the week after infusion
Time frame: Between Hour 0 and day 7
Clinical: Pain area on a body cartography
Evaluation of pain area on a body surface cartography
Time frame: Hour 0, Day 1, Day 7.
Clinical: Ketamine adverse effects
Recording ketamine adverse effects during and right after the infusion
Time frame: Hour 0 to hour 4
Paraclinical: Kynurenine pathway activation with ulcer pressure
Studying the levels of the kynurenine pathway elements between patients with inflammatory component (ulcer pressure) and without inflammatory component (without ulcer pressure)
Time frame: Hour 0
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