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

• ClinicalTrials.gov Identifier: NCT00733096
• Recruitment Status: Completed
• First Posted: August 12, 2008
• Results First Posted: October 8, 2012
• Last Update Posted: October 8, 2012
• Sponsor: Johns Hopkins University
• Collaborators: Walter Reed Army Medical Center; National Naval Medical Center; Womack Army Medical Center; Landstuhl Regional Medical Center; Massachusetts General Hospital
• Information provided by: Johns Hopkins University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Lumbosacral Radiculopathy	Drug: etanercept; Drug: methylprednisolone; Drug: normal saline	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Study Start Date: August 2008
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: March 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Numerical Rating Leg Pain Score [ Time Frame: 1 month ]
   0-10 pain score. 0= no pain, 10= worst imaginable pain.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, District of Columbia

Walter Reed Army Medical Center

Washington, District of Columbia, United States, 20307

United States, North Carolina

Womack Army Medical Center

Fort Bragg, North Carolina, United States

Sponsors and Collaborators

Johns Hopkins University

Walter Reed Army Medical Center

National Naval Medical Center

Womack Army Medical Center

Landstuhl Regional Medical Center

Massachusetts General Hospital

More Information

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. Epub 2005 Jun 22. Review.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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: 10.7326/0003-4819-156-8-201204170-00002.

• Responsible Party: Steven P. cohen, Walter Reed Army Medical Center
• ClinicalTrials.gov Identifier: NCT00733096
• Other Study ID Numbers: 08-6891
• First Posted: August 12, 2008
• Results First Posted: October 8, 2012
• Last Update Posted: October 8, 2012
• Last Verified: September 2010

Keywords provided by Johns Hopkins University:

radiculopathy; sciatica; low back pain

Additional relevant MeSH terms:

Radiculopathy; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Etanercept; Prednisolone hemisuccinate; Prednisolone phosphate; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Antirheumatic Agents