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.
Ketamine's Efficiency in the Treatment of Chronic Pain: Kynurenin Pathway
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.
Intervention / Treatment
Interventional randomized placebo-controlled clinical trial. 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 Ketamine infusion 1 mg / kg IVSE over two hours versus Nacl perfusion 0.9%
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Ketamine 10 MG/ML (DRUG)Ketamine infusion 1mg/kg with electric syringe during 2 hours.
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Placebos (DRUG)Sodium chloride infusion with the same rate, electric syringe during 2 hours.
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Midazolam 1 MG/ML (DRUG)Bolus of Midazolam 1mg before each perfusion.
Condition or Disease
- Neuralgia
- Chronic Pain
- Inflammation
Phase
Study Design
| Study type: | INTERVENTIONAL |
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| Status: | Unknown status |
| Study results: | No Results Available |
| Age: | 18 Years and older (Adult, Older Adult) |
| Enrollment: | 48 (ESTIMATED) |
| Funded by: | Other |
| Allocation: | Randomized |
| Primary Purpose: | Treatment |
MaskingThe randomisation is done with R software. Each randomisation card is put in a sealed opaque envelope. The two products being transparent, it's impossible to differentiate the two products with identical packaging is a syringe of 50 cc Luer Lock Plastipack BD with a standard extension for syringe Luer Lock. Both products will be prepared by an SSPI nurse who opens the envelope, the nurse does not participate in the study, the patient assessment investigator as well as the patient will remain blind about the administration of the product. Each syringe will be labeled for each patient with a special label without indication of the product The outcomes assessor, investigator and participant are blinded. TRIPLE:
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Clinical Trial Dates
| Start date: | Feb 16, 2018 | ACTUAL |
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| Primary Completion: | Oct 01, 2018 | ESTIMATED |
| Completion Date: | Nov 01, 2018 | ESTIMATED |
| Study First Posted: | May 02, 2018 | ACTUAL |
| Results First Posted: | Aug 31, 2020 | |
| Last Updated: | Apr 19, 2018 |
Sponsors / Collaborators
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 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.
Participant Groups
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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.
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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.
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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.
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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.
Eligibility Criteria
| Sex: | All |
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| Minimum Age: | 18 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
Inclusion Criteria:
* 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.
Exclusion Criteria:
* 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.
* 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.
Exclusion Criteria:
* 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.
Primary Outcomes
Secondary Outcomes
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Levels of SEROTONIN (millimoles/liter)
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Levels of KYNURENINE (millimoles/liter)
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Levels of INDOLEAMINE DIOXYGENASE ACTIVITY (division Kynurenine/Tryptophane quote)
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Levels of Kynurenic acid (millimoles/liter)
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Levels of Quinolinic acid (millimoles/liter)
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Levels of Interleukin 1 (picograms/milliliter)
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Levels of Interleukin 6 (picograms/milliliter)
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Levels of TNF alpha (picograms/milliliter)
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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.
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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.
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Self assessment of the global improvement in pain over the week after infusion
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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).
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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.
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Self assessment of the global improvement of the mood over the week after infusion
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Evaluation of pain area on a body surface cartography
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Recording ketamine adverse effects during and right after the infusion
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Studying the levels of the kynurenine pathway elements between patients with inflammatory component (ulcer pressure) and without inflammatory component (without ulcer pressure)
More Details
| NCT Number: | NCT03513822 |
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| Acronym: | KEKU1 |
| Other IDs: | REDAR |
| Study URL: | https://clinicaltrials.gov/study/NCT03513822 |
Last updated: Sep 29, 2023