Lumbar Spinal Fibrosis and TNF Alpha Inhibition

NCT ID: NCT00385086

Last Updated: 2015-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-28
• Study Completion Date: 2014-12-31

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.

Conditions

Post Operative Sciatica by Lumbar Spinal Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TNF-alpha blocker

Treatment with TNF-alpha blocker

Group Type: EXPERIMENTAL

TNF blocker

Intervention Type: DRUG

Treatment with TNF-alpha blocker

Placebo

Treatment with placebo

Group Type: ACTIVE_COMPARATOR

Placebo

Intervention Type: DRUG

Treatment with placebo

Interventions

TNF blocker

Treatment with TNF-alpha blocker

Intervention Type: DRUG

Placebo

Treatment with placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francois Rannou, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hopital Cochin

Paris, Paris, France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 26596627 (View on PubMed)

Other Identifiers

P050312

Identifier Type: -

Identifier Source: org_study_id