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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-003930-10 | EudraCT Number | ||
| protocole ph-03-2018 | Registry Identifier | CPP ILE DE FRANCE X |
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| Name | Class |
|---|---|
| Hôpital Raymond Poincaré | OTHER |
| Hopital Lariboisière | OTHER |
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
| Fondation Apicil |
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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chronic neuropathic pain and bedsore Ketamine group | Active Comparator | 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 | Placebo Comparator | 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 | Active Comparator | 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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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine 10 MG/ML | Drug | Ketamine infusion 1mg/kg with electric syringe during 2 hours. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Numeric 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. | 4 hours after the end of infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Paraclinical: Kynurenine pathway levels : SEROTONIN | Levels of SEROTONIN (millimoles/liter) | Hour 0 and Hour 6 (4 hours after the ending of infusion) |
| Paraclinical: Kynurenine pathway levels : KYNURENINE |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cyril QUEMENEUR, Resident | Contact | 0033681193981 | c.quemeneur@gmx.com | |
| Valeria Martinez, Md, Ph d | Contact | 0033601819222 | valeria.martinez@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Didier Bouhassira, Md, PhD | INSERM U987 | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Raymond Poincaré Hospital | Recruiting | Garches | Hauts De Seine | 92380 | France |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 30, 2017 | Apr 19, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009437 | Neuralgia |
| D059350 | Chronic Pain |
| D007249 | Inflammation |
| D003668 | Pressure Ulcer |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D010146 | Pain |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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| OTHER |
| Hospital Ambroise Paré Paris | OTHER |
| Recherche Clinique Paris Descartes Necker Cochin Sainte Anne | OTHER |
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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The 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.
| Chronic neuropathic pain without bedsore Placebo group | Placebo Comparator | 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. |
|
| 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. |
|
Levels of KYNURENINE (millimoles/liter)
| 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) | Hour 0 and Hour 6 (4 hours after the ending of infusion) |
| Paraclinical: Kynurenine pathway levels : KYNURENIC ACID | Levels of Kynurenic acid (millimoles/liter) | Hour 0 and Hour 6 (4 hours after the ending of infusion) |
| Paraclinical: Kynurenine pathway levels : QUINOLINIC ACID | Levels of Quinolinic acid (millimoles/liter) | Hour 0 and Hour 6 (4 hours after the ending of infusion) |
| Paraclinical: Kynurenine pathway levels : IL1 | Levels of Interleukin 1 (picograms/milliliter) | Hour 0 and Hour 6 (4 hours after the ending of infusion) |
| Paraclinical: Kynurenine pathway levels : IL6 | Levels of Interleukin 6 (picograms/milliliter) | Hour 0 and Hour 6 (4 hours after the ending of infusion) |
| Paraclinical: Kynurenine pathway levels: TNF alpha | Levels of TNF alpha (picograms/milliliter) | 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. | 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. | 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 | 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). | 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. | 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 | Between Hour 0 and day 7 |
| Clinical: Pain area on a body cartography | Evaluation of pain area on a body surface cartography | Hour 0, Day 1, Day 7. |
| Clinical: Ketamine adverse effects | Recording ketamine adverse effects during and right after the infusion | 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) | Hour 0 |
| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
| D012883 | Skin Ulcer |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |