Lumbar Spinal Fibrosis and TNF Alpha Inhibition

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

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.

Study Overview

• Status: Completed
• Conditions: Post Operative Sciatica by Lumbar Spinal Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: TNF blocker

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 Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Hopital Cochin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TNF-alpha blocker; Treatment with TNF-alpha blocker	Drug: TNF blocker; Treatment with TNF-alpha blocker
Active Comparator: Placebo; Treatment with placebo	Drug: Placebo; Treatment with placebo

What is the study measuring?

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	Time Frame
Functional assessments	At 10, 30, 90, 180 days

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Francois Rannou, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Nguyen C, Palazzo C, Grabar S, Feydy A, Sanchez K, Zee N, Quinquis L, Ben Boutieb M, Revel M, Lefevre-Colau MM, Poiraudeau S, Rannou F. Tumor necrosis factor-alpha blockade in recurrent and disabling chronic sciatica associated with post-operative peridural lumbar fibrosis: results of a double-blind, placebo randomized controlled study. Arthritis Res Ther. 2015 Nov 19;17:330. doi: 10.1186/s13075-015-0838-4.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 4, 2006
• First Submitted That Met QC Criteria: October 4, 2006
• First Posted (Estimate): October 6, 2006

Study Record Updates

• Last Update Posted (Estimate): October 16, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Fibrosis; Sciatica; Pain; TNF-alpha; Spine; Discectomy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Sciatic Neuropathy; Mononeuropathies; Peripheral Nervous System Diseases; Neuralgia; Fibrosis; Sciatica; Anti-Inflammatory Agents; Tumor Necrosis Factor Inhibitors
• Other Study ID Numbers: P050312