Efficacy of Epidural Etanercept in the Treatment of Sciatica

Sciatica Clinical Trial

Official title:

Efficacy of Epidural Etanercept in the Treatment of Sciatica

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00364572
• Other study ID #: WU#06-20009A
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 14, 2006
• Last updated: January 21, 2009
• Start date: May 2006
• Est. completion date: December 2007

Study information

• Verified date: January 2009
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Tumor necrosis factor (TNF)-alpha has been strongly implicated as a major contributing factor for the development of radiculopathy. In animal studies, the application of TNF-alpha to nerve roots results in pain behavior indicative of radiculopathy. The use of TNF-alpha inhibitors (etanercept and infliximab) have been shown to prevent this pain behavior. Open-label studies in humans have shown both etanercept and infliximab provide excellent, long-term relief in patients with acute radiculopathy from herniated disc. However, a recent placebo-controlled study failed to demonstrate any significant difference from placebo. The investigators have already established the safety of neuraxial etanercept in a trial that has just been completed (not yet published). The objective of this study is to determine whether small doses of epidural etanercept, an anti-TNF-a medication, is an effective treatment for LBP caused by nerve root irritation (i.e., radiculopathy).

Description:

As per the wishes of the Dept. of the Army and Walter Reed Army Medical Center Dept. of Clinical Investigation, patients will be randomized in a 3:1 ratio to receive 2 transforaminal epidural etanercept or saline injections at 2-week intervals. Both patients and physicians will be blinded as to the injectate and treatment group. There will be 3 study groups. Group I will receive either 2 mg of etanercept or saline per injection. Group II will receive either 4 mg of etanercept or saline per injection. Group III will receive either 6 mg of etanercept or saline per injection. In each group there will be 8 patients: 6 who receive etanercept and 2 who receive saline. As per a previous study we just completed, etanercept doses will not be escalated until all 6 patients have completed their 1-month follow-up visits without any evidence of toxicity or complications.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Chronic low back pain of radicular origin of > 2 months but < 1 year duration.

2. Failure of conservative therapy to include physical and pharmacotherapy.

3. MRI evidence of a herniated disc corresponding to the patient's radicular symptoms.

4. Normal white blood cell count (drawn in 1 blood vial).

Exclusion Criteria:

1. Uncontrolled coagulopathy.

2. Pregnancy, which will be ruled out by a urine pregnancy test if any question as to the patient's status exists.

3. Allergy to contrast dye.

4. Unstable medical condition (e.g., unstable angina or congestive heart failure).

5. Rheumatoid arthritis, Crohn's disease or spondylarthropathy.

6. Unstable neurological condition (e.g., multiple sclerosis)

7. Systemic infection

8. Age < 18 or > 70 years.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sciatica

Intervention

Drug:
• epidural injection of etanercept
2 injections of etanercept 2 weeks apart with doses ranging from 2 mg to 6 mg
• placebo (control procedure)
Two injections of epidural saline 2 weeks apart

Locations

Country	Name	City	State
United States	Walter Reed Army Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Walter Reed Army Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (8)

Cohen SP, Griffith S, Larkin TM, Villena F, Larkin R. Presentation, diagnoses, mechanisms of injury, and treatment of soldiers injured in Operation Iraqi Freedom: an epidemiological study conducted at two military pain management centers. Anesth Analg. 20 — View Citation

Genevay S, Stingelin S, Gabay C. Efficacy of etanercept in the treatment of acute, severe sciatica: a pilot study. Ann Rheum Dis. 2004 Sep;63(9):1120-3. Epub 2004 Apr 28. — View Citation

Igarashi T, Kikuchi S, Shubayev V, Myers RR. 2000 Volvo Award winner in basic science studies: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Molecular, histologic, and behavioral comparisons in rats. Spine (Phila Pa — View Citation

Korhonen T, Karppinen J, Malmivaara A, Autio R, Niinimäki J, Paimela L, Kyllönen E, Lindgren KA, Tervonen O, Seitsalo S, Hurri H. Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up. Spine (Phila Pa 1976). 2004 Oct 1;29(19):211 — View Citation

Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, Järvinen S, Niinimäki J, Veeger N, Seitsalo S, Hurri H. The treatment of disc herniation-induced sciatica with infliximab: results of a randomized, controlled, 3-month follow-up study. Spine ( — View Citation

Olmarker K, Larsson K. Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. Spine (Phila Pa 1976). 1998 Dec 1;23(23):2538-44. — View Citation

Olmarker K, Nutu M, Størkson R. Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-alpha inhibition. Spine (Phila Pa 1976). 2003 Aug 1;28(15):1635-41; discussion 1642. — View Citation

Ozaktay AC, Cavanaugh JM, Asik I, DeLeo JA, Weinstein JN. Dorsal root sensitivity to interleukin-1 beta, interleukin-6 and tumor necrosis factor in rats. Eur Spine J. 2002 Oct;11(5):467-75. Epub 2002 Jun 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Visual analogue scale pain score, Oswestry disability index, medication intake		7 months
Secondary	Global perceived effect, white blood cell count		7 months