Efficacy of Epidural Etanercept in the Treatment of Sciatica - Full Text View

Sponsor:	Johns Hopkins University
Collaborator:	Walter Reed Army Medical Center
Information provided by:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00364572

Purpose

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).

Condition	Intervention	Phase
Sciatica	Drug: epidural injection of etanercept Drug: placebo (control procedure)	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Efficacy of Epidural Etanercept in the Treatment of Sciatica

Resource links provided by NLM:

MedlinePlus related topics: Sciatica

Drug Information available for: Etanercept

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

Visual analogue scale pain score, Oswestry disability index, medication intake [ Time Frame: 7 months ]

Secondary Outcome Measures:

Global perceived effect, white blood cell count [ Time Frame: 7 months ]

Enrollment:	24
Study Start Date:	May 2006
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Two injections of epidural saline 2 weeks apart	Drug: placebo (control procedure) Two injections of epidural saline 2 weeks apart
Epidural injection of etanercept: Experimental Two injections of epidural etanercept 2 weeks apart	Drug: epidural injection of etanercept 2 injections of etanercept 2 weeks apart with doses ranging from 2 mg to 6 mg

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00364572

Locations

United States, District of Columbia
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307

Sponsors and Collaborators

Johns Hopkins University

Walter Reed Army Medical Center

Investigators

Principal Investigator:

Steven P Cohen, MD

Johns Hopkins School of Medicine and Walter Reed Army Medical Center

More Information

Publications:

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.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

Responsible Party:	Walter Reed Army Medical Center ( Steve P. Cohen )
Study ID Numbers:	WU#06-20009A
Study First Received:	August 14, 2006
Last Updated:	January 21, 2009
ClinicalTrials.gov Identifier:	NCT00364572 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Johns Hopkins University:

sciatica
low back pain
epidural
tumor necrosis factor

Additional relevant MeSH terms:

Sciatic Neuropathy
Anti-Inflammatory Agents
Immunologic Factors
Physiological Effects of Drugs
Pain
TNFR-Fc fusion protein
Mononeuropathies
Sciatica
Signs and Symptoms
Neuromuscular Diseases
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal

Analgesics
Neuralgia
Nervous System Diseases
Gastrointestinal Agents
Immunosuppressive Agents
Pharmacologic Actions
Analgesics, Non-Narcotic
Peripheral Nervous System Diseases
Neurologic Manifestations
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 22, 2009