Lumbar Spinal Fibrosis and TNF Alpha Inhibition

Phase 3

Completed

• Conditions: Post Operative Sciatica by Lumbar Spinal Fibrosis
• Interventions: Drug: Placebo; Drug: TNF blocker

• Registration Number: NCT00385086
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2006-10-04
• Study First Submitted QC: 2006-10-04
• Study First Posted: 2006-10-06
• Study Start: 2007-02
• Primary Completion: 2012-10
• Study Completion: 2014-12
• Status Verified: 2015-10
• Last Update Submitted: 2015-10-15
• Last Update Posted: 2015-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Treatment with placebo
TNF-alpha blocker	TNF blocker	Treatment with TNF-alpha blocker

Primary Outcome Measures

Name	Time	Method
Sciatica pain	10 days after treatment	Visual analogue scale of lumbar pain

Secondary Outcome Measures

Name	Time	Method
Functional assessments	At 10, 30, 90, 180 days

Trial Locations

Locations (1)

Hopital Cochin; 🇫🇷 Paris, France