Eplerenone as a Supplement to Epidural Steroid Injections

Epidural Steroid Injection With Supplemental Oral Eplerenone for Low Back Pain: A Prospective, Double Blind Randomized Trial

Low back pain is a leading cause of disability and health care costs in the United States, and treatments are ineffective for many patients. Epidural steroid injections are a common treatment, but their efficacy has been questioned and for many patients they do not provide complete relief. The investigators hypothesize, based on preclinical studies, that lack of complete efficacy may be due to the fact that clinically used steroids activate not only the intended drug target, the glucocorticoid receptor, but also the pro-inflammatory mineralocorticoid receptor. To test this hypothesis, this pilot study will recruit patients scheduled for lumbar epidural steroid injections for degenerative disc disease, and randomize them to receive a concurrent treatment with oral eplerenone (a clinically approved antagonist of the mineralocorticoid receptor) or placebo for 10 days starting just after the epidural injection. At several time points during the following year, subjects will answer the Oswestry Low Back Pain Questionnaire, to report on both pain and functional outcomes.

Study Overview

• Status: Withdrawn
• Conditions: Low Back Pain; Sciatic Radiculopathy; Degenerative Intervertebral Discs
• Intervention / Treatment: Drug: Eplerenone 50 Mg Tab; Drug: Placebo Oral Tablet

Detailed Description

Patients with degenerative disc disease, who are recommended to have an epidural steroid injection at the participating clinics, as part of their routine clinical care, will be invited to participate in the study prior to their first epidural steroid injection. If they consent, they will complete the Oswestry Low Back Pain Questionnaire (version 2) just prior to their first injection which captures the functional effects of back pain on various activities, providing a more meaningful picture than a simple static pain rating.

The subjects will complete the Oswestry Low Back Pain Questionnaire again four weeks after their first injection, a time point at which patients routinely have a follow-up visit. Patients referred for a second injection at this time will complete an additional Oswestry just prior to that injection. Subjects will be asked to complete additional Oswestry Low Back Pain Questionnaires at 3 months, 6 months, 1 year after their epidural injection (or after their second epidural injection if this is recommended).

Prior to receiving study medication (eplerenone or placebo), subjects will provide a blood sample to examine their creatinine and potassium levels, to ensure there are no contraindications to taking eplerenone. C reactive protein levels will also be measured just prior to epidural steroid injections to determine whether this can help predict the response.

In addition to the pain questionnaires, data will be collected from the subjects' medical charts regarding basic clinical demographics and clinical outcome of the epidural steroid injection.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shuchita Garg, MD; Phone Number: 513-475-8282; Email: gargsh@ucmail.uc.edu
• Study Contact Backup: Name: Jun-Ming Zhang, MD MSc; Phone Number: 513-558-2427; Email: jun-ming.zhang@uc.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Health Pain Medicine Center in Clifton
      • Contact: Shuchita Garg, MD; Phone Number: 513-475-8282; Email: gargsh@ucmail.uc.edu
    • West Chester, Ohio, United States, 45069
      • UC Health Pain Medicine Center in West Chester
      • Contact: Shuchita Garg, MD; Phone Number: 513-475-8282; Email: gargsh@ucmail.uc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of lumbar degenerative disc disease demonstrated on either lumbar X-Ray or lumbar MRI.
• radicular symptoms or electromyograph consistent with radiculopathy and exam findings corresponding to this diagnosis
• Scheduled for lumbar epidural steroid injection at participating clinics as part of routine clinical care
• Negative pregnancy test, if of childbearing potential

Exclusion Criteria:

• Unable to complete questionnaires or give informed consent in English
• Unavailable for follow-up contacts to complete questionnaires
• Renal impairment (estimated glomerular filtration rate <50 mL/min or serum creatinine >1.8mg/dL) on metabolic panel obtained just prior to epidural injections.
• Elevated serum potassium (>5.5 milliequivalents/L) on metabolic panel obtained just prior to epidural injections.
• Have undergone previous lumbar surgery within the past year.
• Treated with lumbar epidural steroid injection within the past 3 months at the time of consent.
• Diabetic
• Systolic blood pressure reading less than 100 mm Hg at most recent pain clinic visit.
• Prescribed protease inhibitors.
• Taking strong CYP3A4 inhibitors
• Taking potassium supplements or potassium-sparing diuretics (amiloride, spironolactone, or triamterene) or using salt substitutes that contain potassium (examples given below and in the prescreening document to be used by the study nurse).
• Lactating.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Eplerenone 50 Mg Tab	Drug: Eplerenone 50 Mg Tab; 50 mg PO per day for 10 days; Other Names: Inspra
Placebo Comparator: Control; Placebo Oral Tablet	Drug: Placebo Oral Tablet; PO once daily for 10 days; Other Names: placebo for eplerenone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in Oswestry Low Back Pain Disability Questionnaire at 12 months	back pain disability score ranging from 0 (no disability or pain) to 100% (maximum pain and disability); based on sum of responses to 10 questions each with responses ranging from 0 (no pain/disability) to 5 (maximum pain/disability) expressed as percentage of maximum score.	Difference between score prior to and 12 months after epidural steroid injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
epidural steroid injection clinical outcome	scored as 1 adequate pain relief, no further treatment recommended; 2, partial relief, second injection recommended; 3 little pain relief, alternative treatment recommended	evaluated one month after injection as part of standard clinical care
change in Oswestry Low Back Pain Disability Questionnaire at 4 weeks	back pain disability score ranging from 0 (no disability or pain) to 100% (maximum pain and disability); based on sum of responses to 10 questions each with responses ranging from 0 (no pain/disability) to 5 (maximum pain/disability) expressed as percentage of maximum score.	Difference between score prior to and 4 weeks after epidural steroid injection
change in Oswestry Low Back Pain Disability Questionnaire at 3 months	back pain disability score ranging from 0 (no disability or pain) to 100% (maximum pain and disability); based on sum of responses to 10 questions each with responses ranging from 0 (no pain/disability) to 5 (maximum pain/disability) expressed as percentage of maximum score.	Difference between score prior to and 3 months after epidural steroid injection
change in Oswestry Low Back Pain Disability Questionnaire at 6 months	back pain disability score ranging from 0 (no disability or pain) to 100% (maximum pain and disability); based on sum of responses to 10 questions each with responses ranging from 0 (no pain/disability) to 5 (maximum pain/disability) expressed as percentage of maximum score.	Difference between score prior to and 6 months after epidural steroid injection

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Investigators: Principal Investigator: Shuchita Garg, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: December 6, 2017
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 1, 2018

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: low back pain; degenerative disc disease; radicular pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Musculoskeletal Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Spinal Diseases; Bone Diseases; Back Pain; Low Back Pain; Intervertebral Disc Degeneration; Radiculopathy; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 2017-2713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No