NCT00364572

Brief 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started May 2006

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2006

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

August 14, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 15, 2006

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2007

Completed
Last Updated

January 22, 2009

Status Verified

January 1, 2009

Enrollment Period

1.6 years

First QC Date

August 14, 2006

Last Update Submit

January 21, 2009

Conditions

Sciatica

Keywords

sciaticalow back painepiduraltumor necrosis factor

Outcome Measures

Primary Outcomes (1)

  • Visual analogue scale pain score, Oswestry disability index, medication intake

    7 months

Secondary Outcomes (1)

  • Global perceived effect, white blood cell count

    7 months

Study Arms (2)

1

PLACEBO COMPARATOR

Two injections of epidural saline 2 weeks apart

Drug: placebo (control procedure)

Epidural injection of etanercept

EXPERIMENTAL

Two injections of epidural etanercept 2 weeks apart

Drug: epidural injection of etanercept

Interventions

epidural injection of etanerceptDRUG

2 injections of etanercept 2 weeks apart with doses ranging from 2 mg to 6 mg

Epidural injection of etanercept
placebo (control procedure)DRUG

Two injections of epidural saline 2 weeks apart

1

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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).

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Walter Reed Army Medical Center

Washington D.C., District of Columbia, 20307, United States

Location

Related Publications (9)

  • 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. doi: 10.1007/s00586-002-0430-x. Epub 2002 Jun 4.

    PMID: 12384756RESULT

  • 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. doi: 10.1097/00007632-199812010-00008.

    PMID: 9854752RESULT

  • 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 (Phila Pa 1976). 2003 Aug 1;28(15):1635-41; discussion 1642. doi: 10.1097/01.BRS.0000083162.35476.FF.

    PMID: 12897484RESULT

  • 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 1976). 2000 Dec 1;25(23):2975-80. doi: 10.1097/00007632-200012010-00003.

    PMID: 11145807RESULT

  • 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 (Phila Pa 1976). 2004 Oct 1;29(19):2115-9. doi: 10.1097/01.brs.0000141179.58778.6c.

    PMID: 15454701RESULT

  • 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 (Phila Pa 1976). 2005 Dec 15;30(24):2724-8. doi: 10.1097/01.brs.0000190815.13764.64.

    PMID: 16371894RESULT

  • 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. doi: 10.1136/ard.2003.016451. Epub 2004 Apr 28.

    PMID: 15115710RESULT

  • 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):1098-1103. doi: 10.1213/01.ane.0000169332.45209.cf.

    PMID: 16192528RESULT

  • 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. doi: 10.1097/ALN.0b013e3181a05aa0.

    PMID: 19387178DERIVED

MeSH Terms

Conditions

SciaticaLow Back Pain

Condition Hierarchy (Ancestors)

Sciatic NeuropathyMononeuropathiesPeripheral Nervous System DiseasesNeuromuscular DiseasesNervous System DiseasesNeuralgiaPainNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsBack Pain

Study Officials

  • Steven P Cohen, MD

    Johns Hopkins School of Medicine and Walter Reed Army Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

August 14, 2006

First Posted

August 15, 2006

Study Start

May 1, 2006

Primary Completion

December 1, 2007

Study Completion

December 1, 2007

Last Updated

January 22, 2009

Record last verified: 2009-01

Locations

US(1)