Ketamine's Efficiency in the Treatment of Chronic Pain: Kynurenin Pathway

NCT03513822 | Unknown Phase 3

• 3 other identifiers: REDAR2017-003930-10protocole ph-03-2018
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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. 1.To show a better clinical efficacy of ketamine in chronic pain in patients with an inflammatory component.
2. 2.Explore the anti-inflammatory activity of ketamine through the Kynurenine pathway.

Conditions

Neuralgia; Chronic Pain; Inflammation

Keywords

KETAMINE; CHRONIC PAIN; NEUROPATHIC PAIN; KYNURENINE; KYNURENINE PATHWAY; BEDSORES; ANTI-INFLAMMATORY; ULCER PRESSURE

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (17)

• Paraclinical: Kynurenine pathway levels : SEROTONIN

  Hour 0 and Hour 6 (4 hours after the ending of infusion)

• Paraclinical: Kynurenine pathway levels : KYNURENINE

  Hour 0 and Hour 6 (4 hours after the ending of infusion)

• Paraclinical: Kynurenine pathway levels : IDO ACTIVITY

  Hour 0 and Hour 6 (4 hours after the ending of infusion)

• Paraclinical: Kynurenine pathway levels : KYNURENIC ACID

  Hour 0 and Hour 6 (4 hours after the ending of infusion)

• Paraclinical: Kynurenine pathway levels : QUINOLINIC ACID

  Hour 0 and Hour 6 (4 hours after the ending of infusion)

Study Arms (4)

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.

Drug: Ketamine 10 MG/ML; Drug: Midazolam 1 MG/ML

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.

Drug: Placebos; Drug: Midazolam 1 MG/ML

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.

Drug: Ketamine 10 MG/ML; Drug: Midazolam 1 MG/ML

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.

Drug: Placebos; Drug: Midazolam 1 MG/ML

Interventions

Ketamine 10 MG/ML DRUG

Ketamine infusion 1mg/kg with electric syringe during 2 hours.

Chronic neuropathic pain and bedsore Ketamine group; Chronic neuropathic pain without bedsore Ketamine group

Placebos DRUG

Sodium chloride infusion with the same rate, electric syringe during 2 hours.

Also known as: Sodium chloride infusion

Chronic neuropathic pain and bedsore Placebo group; Chronic neuropathic pain without bedsore Placebo group

Midazolam 1 MG/ML DRUG

Bolus of Midazolam 1mg before each perfusion.

Chronic neuropathic pain and bedsore Ketamine group; Chronic neuropathic pain and bedsore Placebo group; Chronic neuropathic pain without bedsore Ketamine group; Chronic neuropathic pain without bedsore Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults speaking and understanding French
• presenting chronic neuropathic pain as defined by IASP
• Able to give informed consent, after clear, fair and appropriate information
• Having given their consent by a written consent signature.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Redar: lead
• Hôpital Raymond Poincaré: collaborator
• Hopital Lariboisière: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Fondation Apicil: collaborator
• Hospital Ambroise Paré Paris: collaborator
• Recherche Clinique Paris Descartes Necker Cochin Sainte Anne: collaborator

Study Sites (1)

Raymond Poincaré Hospital

Garches, Hauts De Seine, 92380, France

RECRUITING

MeSH Terms

Conditions

Neuralgia; Chronic Pain; Inflammation; Pressure Ulcer

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Didier Bouhassira, Md, PhD

  INSERM U987

  STUDY CHAIR

Central Study Contacts

Cyril QUEMENEUR, Resident

CONTACT

0033681193981; c.quemeneur@gmx.com

Valeria Martinez, Md, Ph d

CONTACT

0033601819222; valeria.martinez@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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%

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: May 2, 2018
• Study Start: February 16, 2018
• Primary Completion: October 1, 2018
• Study Completion: November 1, 2018
• Last Updated: May 2, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)