Lumbar Spinal Fibrosis and TNF Alpha Inhibition

Study Overview
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Brief Summary
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TNF-alpha is the main cytokine implicated in the formation of lumbar spinal fibrosis. Inhibiting TNF-alpha could significantly decrease spinal fibrosis after lumbar discectomy.

Detailed Description
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OBJECT: Failed back surgery syndrome is still a challenging therapeutic problem. Clinical studies have demonstrated a significant association between lumbar spinal fibrosis after lumbar discectomy and the recurrence of radicular pain in 25% of cases. Forceful epidural infiltrations, radiotherapy, therapy with D-penicillamine or surgical procedures have had unfavourable results in terms of pain and cost. Magnetic resonance imaging reveals lumbar spinal fibrosis by a hyposignal in the T1 sequence and a hypersignal in T2 sequence around the spinal tissue. Tumor necrosis factor a (TNF-a) is the main cytokine implicated in the formation of tissue fibrosis. In animal models of fibrosis, TNF-a inhibition has been shown to prevent and treat tissue fibrosis. HYPOTHESIS: Inhibiting TNF-a could significantly decrease sciatica pain because of lumbar spinal fibrosis after lumbar discectomy by decreasing spinal fibrosis. METHODS: We propose a 2-year pilot prospective, randomized, double-blind, controlled study of TNF-a inhibitor (infliximab) in patients with sciatica as a result of postoperative lumbar spinal fibrosis. The infliximab group will receive one intravenous injection of 3 mg/kg infliximab. The control group will receive one physiological serum injection. Patients will be evaluated at day 0, 10, 30, 90, and 180. The main evaluation criterion will be sciatica pain as measured on a visual analog scale, with the objective of a 50% decrease in pain at day 10. This objective leads to a size of 20 patients per group. The other evaluation criteria will be clinical, functional, social, and professional. Patients will be recruited from the rehabilitation unit at Cochin teaching hospital.

Official Title
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Efficacy of TNF-alpha Inhibition in Sciatica With Post-operative Lumbar Spinal Fibrosis

Conditions
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Post Operative Sciatica by Lumbar Spinal Fibrosis

Intervention / Treatment
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* Drug: TNF blocker
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 years old sciatica post discectomy Pain with VAS > 40 mm and impossibility to have his usual activity Surgical discectomy (less than 2 years and more than 6 months) Painless of more than one month and less than one year after the discectomy MRI with gadolinium injection of less than 6 months and done more than 6 months after the discectomy Presence of spinal fibrosis on MRI (hyposignal in T1 enhanced by gadolinium and hypersignal in T2) failure of epidural injection treatment absence of tuberculosis contraception for woman informed consent Exclusion Criteria: Chronic psychiatric pathologies not treated Presence of conflict between nerve root and herniated disc or disc fragments or spinal stenosis severe cognitives troubles severe cardiac failure (class III or IV) Tuberculosis (active or latent), severe infections Cancers Allergy reactions to the drug studied Difficulties to understand french Patients enrolled in another clinical trial in the past three months pregnancy, breastfeeding or no contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNF-alpha blocker<br>Treatment with TNF-alpha blocker | Drug: TNF blocker<br>* Treatment with TNF-alpha blocker<br>|
| Active Comparator: Placebo<br>Treatment with placebo | Drug: Placebo<br>* Treatment with placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sciatica pain | Visual analogue scale of lumbar pain | 10 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional assessments |  | At 10, 30, 90, 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Sciatica, TNF-alpha, Discectomy, Fibrosis, Spine