Lumbar Spinal Fibrosis and TNF Alpha Inhibition

• ClinicalTrials.gov Identifier: NCT00385086
• Recruitment Status: Completed
• First Posted: October 6, 2006
• Last Update Posted: October 16, 2015
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Post Operative Sciatica by Lumbar Spinal Fibrosis	Drug: TNF blocker; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of TNF-alpha Inhibition in Sciatica With Post-operative Lumbar Spinal Fibrosis
• Study Start Date: February 2007
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: December 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Sciatica pain [ Time Frame: 10 days after treatment ]
   Visual analogue scale of lumbar pain

Secondary Outcome Measures :

1. Functional assessments [ Time Frame: At 10, 30, 90, 180 days ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

France

Hopital Cochin

Paris, France, 75014

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nguyen C, Palazzo C, Grabar S, Feydy A, Sanchez K, Zee N, Quinquis L, Ben Boutieb M, Revel M, Lefèvre-Colau MM, Poiraudeau S, Rannou F. Tumor necrosis factor-α 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.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT00385086
• Other Study ID Numbers: P050312
• First Posted: October 6, 2006
• Last Update Posted: October 16, 2015
• Last Verified: October 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Sciatica; Pain; TNF-alpha; Discectomy; Fibrosis; Spine

Additional relevant MeSH terms:

Sciatica; Fibrosis; Pathologic Processes; Sciatic Neuropathy; Mononeuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuralgia; Pain; Neurologic Manifestations