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

Tracking Information

• First Submitted Date: October 4, 2006
• First Posted Date: October 6, 2006
• Last Update Posted Date: October 16, 2015
• Study Start Date: February 2007
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 25, 2012)

Sciatica pain [ Time Frame: 10 days after treatment ]

Visual analogue scale of lumbar pain

• Original Primary Outcome Measures (submitted: October 4, 2006): Sciatica pain
• Current Secondary Outcome Measures (submitted: July 25, 2012): Functional assessments [ Time Frame: At 10, 30, 90, 180 days ]
• Original Secondary Outcome Measures (submitted: October 4, 2006): Functional assessments
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lumbar Spinal Fibrosis and TNF Alpha Inhibition
• Official Title: Efficacy of TNF-alpha Inhibition in Sciatica With Post-operative Lumbar Spinal Fibrosis
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Post Operative Sciatica by Lumbar Spinal Fibrosis

Intervention

• Drug: TNF blocker
  Treatment with TNF-alpha blocker
• Drug: Placebo
  Treatment with placebo

Study Arms

• Experimental: TNF-alpha blocker
  Treatment with TNF-alpha blocker
  Intervention: Drug: TNF blocker
• Active Comparator: Placebo
  Treatment with placebo
  Intervention: Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 15, 2015): 38
• Original Enrollment (submitted: October 4, 2006): 40
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00385086
• Other Study ID Numbers: P050312
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Assistance Publique - Hôpitaux de Paris
• Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Not Provided

Investigators

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

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: October 2015