| August 14, 2006 |
| January 21, 2009 |
| May 2006 |
| December 2007 (final data collection date for primary outcome measure) |
| Visual analogue scale pain score, Oswestry disability index, medication intake [ Time Frame: 7 months ] |
| Visual analogue scale pain score Oswestry disability index, medication intake |
| Complete list of historical versions of study NCT00364572 on ClinicalTrials.gov Archive Site |
| Global perceived effect, white blood cell count [ Time Frame: 7 months ] |
| Global perceived effect, white blood cell count |
| |
| Efficacy of Epidural Etanercept in the Treatment of Sciatica |
| Efficacy of Epidural Etanercept in the Treatment of Sciatica |
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). |
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. |
| Phase I, Phase II |
| Interventional |
| Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
| Sciatica |
- Drug: epidural injection of etanercept
- Drug: placebo (control procedure)
|
- Placebo Comparator: Two injections of epidural saline 2 weeks apart
- Experimental: Two injections of epidural etanercept 2 weeks apart
|
- 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.
- Olmarker K, Larsson K. Tumor necrosis factor alpha and nucleus-pulposus-induced nerve root injury. Spine. 1998 Dec 1;23(23):2538-44.
- Olmarker K, Nutu M, Storkson R. Changes in spontaneous behavior in rats exposed to experimental disc herniation are blocked by selective TNF-alpha inhibition. Spine. 2003 Aug 1;28(15):1635-41; discussion 1642.
- 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. 2000 Dec 1;25(23):2975-80.
- Korhonen T, Karppinen J, Malmivaara A, Autio R, Niinimaki J, Paimela L, Kyllonen E, Lindgren KA, Tervonen O, Seitsalo S, Hurri H. Efficacy of infliximab for disc herniation-induced sciatica: one-year follow-up. Spine. 2004 Oct 1;29(19):2115-9.
- Korhonen T, Karppinen J, Paimela L, Malmivaara A, Lindgren KA, Jarvinen S, Niinimaki 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. 2005 Dec 15;30(24):2724-8.
- 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.
- 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. 2005 Oct;101(4):1098-103, table of contents.
- Cohen SP, Bogduk N, Dragovich A, Buckenmaier CC 3rd, Griffith S, Kurihara C, Raymond J, Richter PJ, Williams N, Yaksh TL. Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology. 2009 May;110(5):1116-26.
|
| |
| Completed |
| 24 |
| December 2007 |
| December 2007 (final data collection date for primary outcome measure) |
Inclusion Criteria:
- Chronic low back pain of radicular origin of > 2 months but < 1 year duration.
- Failure of conservative therapy to include physical and pharmacotherapy.
- MRI evidence of a herniated disc corresponding to the patient's radicular symptoms.
- Normal white blood cell count (drawn in 1 blood vial).
Exclusion Criteria:
- Uncontrolled coagulopathy.
- Pregnancy, which will be ruled out by a urine pregnancy test if any question as to the patient's status exists.
- Allergy to contrast dye.
- Unstable medical condition (e.g., unstable angina or congestive heart failure).
- Rheumatoid arthritis, Crohn's disease or spondylarthropathy.
- Unstable neurological condition (e.g., multiple sclerosis)
- Systemic infection
- Age < 18 or > 70 years.
|
| Both |
| 18 Years to 70 Years |
| No |
| Contact information is only displayed when the study is recruiting subjects |
| United States |
| |
| NCT00364572 |
| Steve P. Cohen, Walter Reed Army Medical Center |
| WU#06-20009A |
| Johns Hopkins University |
| Walter Reed Army Medical Center |
| Principal Investigator: |
Steven P Cohen, MD |
Johns Hopkins School of Medicine and Walter Reed Army Medical Center |
|
|
| Johns Hopkins University |
| January 2009 |