Clinical trial NCT03513822: Ketamine's Efficiency in the Treatment of Chronic Pain: Kynurenin Pathway
Official title: Ketamine's Efficiency in the Treatment of Chronic Pain With an Added Inflammatory Component Exploring the Kynurenin Pathway. A Randomized, Double Blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Neuralgia
Chronic Pain
Inflammation
Keywords: KETAMINE
CHRONIC PAIN
NEUROPATHIC PAIN
KYNURENINE
KYNURENINE PATHWAY
BEDSORES
ANTI-INFLAMMATORY
ULCER PRESSURE
Lead sponsor: Redar
Sponsor class: OTHER
Collaborators: name: Hôpital Raymond Poincaré
name: Hopital Lariboisière
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Fondation Apicil
name: Hospital Ambroise Paré Paris
name: Recherche Clinique Paris Descartes Necker Cochin Sainte Anne
First posted: 2018-05-02
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Numeric pain rating scale decrease between H0 and H4.
timeFrame: 4 hours after the end of infusion
Secondary outcomes:
measure: Paraclinical: Kynurenine pathway levels : SEROTONIN
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels : KYNURENINE
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels : IDO ACTIVITY
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels : KYNURENIC ACID
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels : QUINOLINIC ACID
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels : IL1
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels : IL6
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Paraclinical: Kynurenine pathway levels: TNF alpha
timeFrame: Hour 0 and Hour 6 (4 hours after the ending of infusion)
measure: Clinical: Neuropathic pain symptom inventory
timeFrame: Hour 0, Day 1, Day 4, Day 7
measure: Clinical: Pain timeline
timeFrame: Seven days
measure: Percentage overall improvement in pain over a week with self assessment
timeFrame: Between Hour 0 and Day 7
measure: Clinical: Subscore of Neuropathic pain symptom inventory
timeFrame: Hour 0, Day 1, Day 4, Day 7
measure: Clinical: Hospital anxiety and depression scale
timeFrame: Hour 0, Day 7.
measure: Percentage overall improvement in mood over a week with self assessment
timeFrame: Between Hour 0 and day 7
measure: Clinical: Pain area on a body cartography
timeFrame: Hour 0, Day 1, Day 7.
measure: Clinical: Ketamine adverse effects
timeFrame: Hour 0 to hour 4
measure: Paraclinical: Kynurenine pathway activation with ulcer pressure
timeFrame: Hour 0
Other outcomes:
Locations:
city: Garches
country: France
facility: Raymond Poincaré Hospital
state: Hauts De Seine
Study officials:
affiliation: INSERM U987
name: Didier Bouhassira, Md, PhD
role: STUDY_CHAIR
References: