A 3-arm Multi-center, Randomized Controlled Study Comparing Transforaminal Corticosteroid, Transforaminal Etanercept and Transforaminal Saline for Lumbosacral Radiculopathy

Lumbosacral radiculopathy is one of the leading of cause of disability in the U.S. and worldwide. Among recent reviews evaluating epidural steroid injections, some 1 but not all 2 concluded them to be effective in the long-term. In our own double-blind, placebo-controlled study evaluating epidural etanercept, the results showed significant benefit in favor of the etanercept group, but no subject was included with a duration of pain > 9 months, and the results of this study have yet to be replicated.

Currently, epidural steroid injections are the most frequently performed procedures in pain clinics across the U.S. However, epidural steroids may benefit only a select group of patients. The literature on treating sciatica is notable for a lack of randomized comparative studies involving various treatments. The objective of this project is to conduct a 3-arm study to determine the efficacy of 1) transforaminal epidural corticosteroids; and 2) transforaminal epidural etanercept, in patients with lumbosacral radiculopathy.

Study Overview

• Status: Completed
• Conditions: Lumbosacral Radiculopathy
• Intervention / Treatment: Drug: etanercept; Drug: methylprednisolone; Drug: normal saline

Detailed Description

This is a 3-arm multi-center, randomized, double-blind, placebo-controlled study comparing two treatments with transforaminal epidural saline. Each group will receive a 2nd procedure identical to the first 2 weeks after the initial procedure.

Seventy-eight study participants will be randomized via a computerized randomization system using SPSS software in groups of 6 at each institution by a research nurse not involved in patient care. There will be 26 patients in each of the 3 groups. A physician unaware of the patient's treatment group will place 22-gauge needles in the relevant foramen under fluoroscopic guidance as determined by patient's symptoms and MRI findings. Once correct placement is confirmed by contrast injection, the blinded physician will leave the room and another physician will inject the medication. In group I, this will be 60 mg of depo-methylprednisolone. In group II, this will be 4 mg of etanercept reconstituted in 2 ml of sterile water. In group III, this will be normal saline.

Two weeks after the initial procedure, an identical procedure to the first one will be done by the same physician or his designate. In addition to the study medication, each patient in each group will receive 0.5 ml of 0.5% bupivacaine local anesthetic for immediate pain relief during both injections before the study drug is delivered. The efficacy of blinding will be assessed by a disinterested observer unaware of the randomization results after the second procedure before discharge. Follow-up visits will be conducted one, three and six months after the second injection, for those subjects who continue to experience > 50% pain relief.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center
  • North Carolina
    • Fort Bragg, North Carolina, United States
      • Womack Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Chronic low back pain of radicular origin of > 4 weeks but < 6 months duration.
2. Leg pain > back pain.
3. Failure of conservative therapy to include physical and pharmacotherapy.
4. MRI evidence of a lateral or paracentral herniated disc corresponding to the patient's radicular symptoms.

Exclusion Criteria:

1. Uncontrolled coagulopathy.
2. Pregnancy, which will be ruled out by a urine pregnancy test in women of childbearing age.
3. Allergy to contrast dye or amide local anesthetics.
4. Previous epidural steroid injection within last year.
5. Unstable medical or psychiatric condition (e.g. unstable angina, congestive heart failure or severe depression) that could preclude an optimal treatment response.
6. Rheumatoid arthritis or spondylarthropathy.
7. Unstable neurological condition (e.g. multiple sclerosis)
8. Systemic infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Epidural etanercept 4 mg, two doses 2 weeks apart	Drug: etanercept; Two transforaminal epidural injections of 4 mg, two weeks apart
Active Comparator: 2; Epidural methylprednisolone 60 mg, two doses 2 weeks apart	Drug: methylprednisolone; Two transforaminal epidural steroid injections with 60 mg, two weeks apart
Placebo Comparator: 3; Epidural saline, two doses 2 weeks apart	Drug: normal saline; Two transforaminal epidural saline injections, two weeks apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical Rating Leg Pain Score	0-10 pain score. 0= no pain, 10= worst imaginable pain.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oswestry Disability Score	0-100%. 0= no disability, 100% is complete disability	1 month
Global Perceived Effect	Satisfaction. Number of participants with positive perceived global satisfaction.	1 month
Medication Reduction	Number of people who reduced medications	1 month

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Massachusetts General Hospital; Walter Reed Army Medical Center; Womack Army Medical Center; Landstuhl Regional Medical Center; National Naval Medical Center

Publications and helpful links

General Publications

• Mulleman D, Mammou S, Griffoul I, Watier H, Goupille P. Pathophysiology of disk-related sciatica. I.--Evidence supporting a chemical component. Joint Bone Spine. 2006 Mar;73(2):151-8. doi: 10.1016/j.jbspin.2005.03.003. Epub 2005 Jun 22.
• Cohen SP, White RL, Kurihara C, Larkin TM, Chang A, Griffith SR, Gilligan C, Larkin R, Morlando B, Pasquina PF, Yaksh TL, Nguyen C. Epidural steroids, etanercept, or saline in subacute sciatica: a multicenter, randomized trial. Ann Intern Med. 2012 Apr 17;156(8):551-9. doi: 10.7326/0003-4819-156-8-201204170-00397.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 11, 2008
• First Submitted That Met QC Criteria: August 11, 2008
• First Posted (Estimate): August 12, 2008

Study Record Updates

• Last Update Posted (Estimate): October 8, 2012
• Last Update Submitted That Met QC Criteria: October 5, 2012
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: low back pain; radiculopathy; sciatica
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Radiculopathy; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Etanercept
• Other Study ID Numbers: 08-6891