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

NCT ID: NCT03513822

Last Updated: 2018-05-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-16

Study Completion Date

2018-11-30

Brief Summary

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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:

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

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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:

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.

Conditions

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Neuralgia Chronic Pain Inflammation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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%
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
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.

Study Groups

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Chronic neuropathic pain and bedsore Ketamine group

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.

Group Type ACTIVE_COMPARATOR

Ketamine 10 MG/ML

Intervention Type DRUG

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

Midazolam 1 MG/ML

Intervention Type DRUG

Bolus of Midazolam 1mg before each perfusion.

Chronic neuropathic pain and bedsore Placebo group

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.

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

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

Midazolam 1 MG/ML

Intervention Type DRUG

Bolus of Midazolam 1mg before each perfusion.

Chronic neuropathic pain without bedsore Ketamine group

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.

Group Type ACTIVE_COMPARATOR

Ketamine 10 MG/ML

Intervention Type DRUG

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

Midazolam 1 MG/ML

Intervention Type DRUG

Bolus of Midazolam 1mg before each perfusion.

Chronic neuropathic pain without bedsore Placebo group

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.

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

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

Midazolam 1 MG/ML

Intervention Type DRUG

Bolus of Midazolam 1mg before each perfusion.

Interventions

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Ketamine 10 MG/ML

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

Intervention Type DRUG

Placebos

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

Intervention Type DRUG

Midazolam 1 MG/ML

Bolus of Midazolam 1mg before each perfusion.

Intervention Type DRUG

Other Intervention Names

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Sodium chloride infusion

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hôpital Raymond Poincaré

OTHER

Sponsor Role collaborator

Hopital Lariboisière

OTHER

Sponsor Role collaborator

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

Fondation Apicil

OTHER

Sponsor Role collaborator

Hospital Ambroise Paré Paris

OTHER

Sponsor Role collaborator

Recherche Clinique Paris Descartes Necker Cochin Sainte Anne

OTHER

Sponsor Role collaborator

Redar

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Didier Bouhassira, Md, PhD

Role: STUDY_CHAIR

INSERM U987

Locations

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Raymond Poincaré Hospital

Garches, Hauts De Seine, France

Site Status RECRUITING

Countries

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France

Central Contacts

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Cyril QUEMENEUR, Resident

Role: CONTACT

0033681193981

Valeria Martinez, Md, Ph d

Role: CONTACT

0033601819222

Facility Contacts

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Cyril QUEMENEUR, Resident

Role: primary

0033681193981

Valeria Martinez, MD, PhD

Role: backup

0033601819222

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-003930-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

protocole ph-03-2018

Identifier Type: REGISTRY

Identifier Source: secondary_id

REDAR

Identifier Type: -

Identifier Source: org_study_id

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